Papers - Sugai, Takeshi

Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy

Ito C., Taguchi K., Yamada T., Hanaya K., Enoki Y., Sugai T., Komatsu T., Matsumoto K.

Journal of Materials Chemistry B 12 ( 23 ) 5600 - 5608 2024.05

ISSN  2050750X

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A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

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Synthesis and luminescence properties of substituted benzils

Yasui M., Fujihara T., Ohtsu H., Wada Y., Shimada T., Zhu Y., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

Communications Chemistry 6 ( 1 )  2023.12

Research paper (scientific journal), Accepted

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Photophysical properties of benzil (1,2-diphenylethane-1,2-dione) and its derivatives in the crystal state have recently attracted much attention. However, the study of substituted benzils has mostly been limited to para-substituted derivatives, which did not induce a significant effect on the emission wavelength compared to pristine benzil. The effects of ortho- and meta-substituents on the photophysical properties in the crystal state have not been investigated so far. Our recently developed organocatalytic pinacol coupling of substituted benzaldehydes allowed us to prepare various ortho-, meta-, and para-substituted benzil derivatives and to investigate their luminescence properties. Ortho- and meta-substituents affected the electronic states of benzils in the crystal state, resulting in differences in their luminescence properties. The luminescence wavelength and type, i.e., phosphorescence or fluorescence, were altered by these substituents. Fast self-recovering phosphorescence-to-phosphorescence mechanochromism by the para-CF3 substituent at room temperature was also discovered.

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Unified short syntheses of oxygenated tricyclic aromatic diterpenes by radical cyclization with a photoredox catalyst

Hashimoto R., Hanaya K., Sugai T., Higashibayashi S.

Communications Chemistry 6 ( 1 )  2023.12

Research paper (scientific journal), Accepted

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The biomimetic two-phase strategy employing polyene cyclization and subsequent oxidation/substitution is an effective approach for divergent syntheses of [6-6-6]-tricyclic diterpenes. However, this strategy requires lengthy sequences for syntheses of oxygenated tricyclic aromatic abietane/podocarpane diterpenes owing to the many linear oxidation/substitution steps after cyclization. Here, we present a new synthetic route based on a convergent reverse two-phase strategy employing a reverse radical cyclization approach, which enabled the unified short syntheses of four aromatic abietane/podocarpane diterpenes and the divergent short syntheses of other related diterpenes. Oxygenated and substituted precursors for cyclization were convergently prepared through Friedel-Crafts acylation and rhodium-catalyzed site-selective iodination. Radical redox cyclization using an iridium photoredox catalyst involving neophyl rearrangement furnished the thermodynamically favored 6-membered ring preferentially. (±)-5,6-Dehydrosugiol, salvinolone, crossogumerin A, and Δ5-nimbidiol were synthesized in only 8 steps. An oxygenated cyclized intermediate was also useful for divergent derivatization to sugiol, ferruginol, saprorthoquinone, cryptomeriololide, and salvinolone.

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Selective modification of tryptophan in polypeptides via C-N coupling with azoles using in situ-generated iodine-based oxidants in aqueous media

Watanabe S., Wada Y., Kawano M., Higashibayashi S., Sugai T., Hanaya K.

Chemical Communications 59 ( 87 ) 13026 - 13029 2023.10

Research paper (scientific journal), Accepted,  ISSN  13597345

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This study demonstrates the C-N coupling of tryptophan with azoles, promoted by an in situ-generated iodine-based oxidant. The protocol was successfully applied to the selective modification of tryptophan in nonprotected polypeptide bearing oxidatively sensitive residues in acidic aqueous media. The present method allows the attachment of reactive handles to polypeptides and the peptide stapling.

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Inversion of Diaza[5]Helicenes Through an N−N Bond Breaking Pathway

Kobayashi T., Ishiwari F., Fukushima T., Nojima Y., Hasegawa M., Mazaki Y., Hanaya K., Sugai T., Higashibayashi S.

Chemistry - A European Journal 29 ( 43 )  2023.08

Research paper (scientific journal), Accepted,  ISSN  09476539

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1,1’,10,10’-Biphenothiazine and its S,S,S’,S’-tetroxide are diaza[5]helicenes with N−N linkages. Kinetic experiments on racemization together with DFT calculations revealed that they undergo inversion through the N−N bond breaking pathway rather than the general conformational pathway. In these diaza[5]helicenes with this inversion mechanism, the reduction of electronic repulsion in the N−N bond by modification of S to SO2 at the outer position of the helix led to a significantly higher inversion barrier, 35.3 kcal/mol, compared to [5]helicene. 1,1’,10,10’-Biphenothiazine S,S,S’,S’-tetroxide was highly resistant to acid-mediated N−N bond breaking and racemization under acidic conditions.

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Intramolecular cyclization of m-homoprenylphenols through oxidative nucleophilic aromatic substitution

Deguchi H., Hanaya K., Sugai T., Higashibayashi S.

Chemical Communications 59 ( 6 ) 748 - 751 2022.12

Research paper (scientific journal), Accepted,  ISSN  13597345

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We developed an intramolecular cyclization of m-homoprenylphenols and related m-prenylphenols to bicyclic skeletons by hypervalent iodine reagents through an oxidative nucleophilic aromatic substitution using the prenyl group as a carbon nucleophile. The reaction was applicable for the syntheses of 5/6-, 6/6-, and 7/6-fused ring systems.

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Copper-Catalyzed Stereoselective Borylation and Palladium-Catalyzed Stereospecific Cross-Coupling to Give Aryl C-Glycosides

Kurahayashi K., Hanaya K., Sugai T., Hirai G., Higashibayashi S.

Chemistry - A European Journal 29 ( 6 )  2022.12

Research paper (scientific journal), Accepted

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Metabolically stable C-glycosides are an essential family of compounds in bioactive natural products, therapeutic agents, and biological probes. For their application, development of synthetic methods by connecting glycosides and aglycons with strict stereocontrol at the anomeric carbon, as well as with high functional-group compatibility and environmental compatibility is a pivotal issue. Although Suzuki–Miyaura-type C(sp3)−C(sp2) cross-coupling using glycosyl boronates is a potential candidate for the construction of C-glycosides, neither the cross-coupling itself nor the facile synthesis of the coupling precursor, glycosyl boronates, have been achieved to date. Herein, it was succeeded to develop a copper-catalyzed stereoselective one-step borylation of glycosyl bromides to glycosyl boronates and palladium-catalyzed stereospecific cross-coupling of β-glycosyl borates with aryl bromides to give aryl β-C-glycosides, in which the β-configuration of the anomeric carbon of the glycosyl trifluoroborates is stereoretentively transferred to that of the resulting aryl C-glycosides.

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Chemoselectivity-independent Cu-mediated coupling to construct the hydroquinoline skeleton of symbioimine

Fujita R., Hanaya K., Sugai T., Higashibayashi S.

Scientific Reports 11 ( 1 )  2022.12

Research paper (scientific journal), Accepted

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Construction of the hydroquinoline skeleton of symbioimine by Cu-mediated N-alkenylation or O-alkenylation of an allyl aminoalcohol, in which either chemoselectivity could lead to the target compound, was investigated. O-alkenylation followed by Claisen rearrangement was favored with high selectivity under a ligand-free condition. Subsequent intramolecular condensation furnished the hydroquinoline skeleton of symbioimine.

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Transition-metal-free β-selective C-glycosylation of β-glycosyl boronate via stereoretentive 1,2-migration

Hiroki Yasutomi, Daiki Takeda, Makoto Yoritate, Shuhei Higashibayashi, Takeshi Sugai, Go Hirai

Synlett 34   347 - 352 2022.11

Research paper (scientific journal), Accepted

Single-Step N-Terminal Modification of Proteins via a Bio-Inspired Copper(II)-Mediated Aldol Reaction

Hanaya K., Yamoto K., Taguchi K., Matsumoto K., Higashibayashi S., Sugai T.

Chemistry - A European Journal 28 ( 47 ) 347 - 352 2022.08

Research paper (scientific journal), Last author, Accepted

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The chemical modification of proteins is an effective technique for manipulating the properties and functions of proteins, and for creating protein-based materials. The N-terminus is a promising target for single-site modification that provides modified proteins with uniform structures and properties. In this paper, a copper(II)-mediated aldol reaction with 2-pyridinecarboxaldehyde (2-PC) derivatives is proposed as an operationally simple method to selectively modify the N-terminus of peptides and proteins at room temperature and physiological pH. The copper(II) ion activates the N-terminal amino acids by complexation with an imine of the N-terminal amino acid and 2-PCs, realizing the selective formation of the nucleophilic intermediate at the N-terminus. This results in a stable carbon-carbon bond between the 2-PCs and the α-carbon of various N-terminal amino acids. The reaction is applied to four different proteins, including biopharmaceuticals such as filgrastim and trastuzumab. The modified trastuzumab retains the human epidermal growth factor receptor 2 recognition activity.

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One-Step Synthesis of Acylborons from Acyl Chlorides through Copper-Catalyzed Borylation with Polystyrene-Supported PPh<inf>3</inf>Ligand

Nakahara M., Kurahayashi K., Hanaya K., Sugai T., Higashibayashi S.

Organic Letters 24 ( 30 ) 5596 - 5601 2022.08

Research paper (scientific journal), Accepted

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We developed a one-step synthesis of acylborons from both readily available acyl chlorides and bis(pinacolato)diboron through copper(I)-catalyzed borylation. Under the reaction conditions using tBuOLi, polystyrene-supported triphenylphosphine as a copper ligand was found to promote the borylation of acyl chlorides while suppressing alcoholysis. This method enables the facile synthesis of potassium acyltrifluoroborates.

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1,2-Rearrangement from o-Quinols to Multisubstituted Catechols via Retro Diels-Alder Reaction of o-Quinol Dimers

Hashimoto R., Hanaya K., Sugai T., Higashibayashi S.

Bulletin of the Chemical Society of Japan 95 ( 4 ) 663 - 672 2022.04

Research paper (scientific journal), Accepted

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The 1,2-rearrangement of o-quinols has been a long-standing unsolved problem since 1958. Although the rearrangement is expected to be useful for syntheses of catechol derivatives, it is hampered by many competing reactions and has not been developed as a useful methodology. Here, we succeeded in settling this problem by a first systematic thorough investigation, establishing the 1,2-rearrangement as a cascade reaction with a retro Diels-Alder reaction from o-quinol dimers. This is a useful strategy for syntheses of substituted catechols used as synthetic building blocks for bioactive compounds and material molecules. o-Quinol dimers were synthesized by improved oxidative hydroxylation of substituted phenols followed by spontaneous Diels-Alder reaction. The dimers then underwent the retro Diels-Alder reaction to regenerate the o-quinols followed by 1,2-rearrangement under neutral heating conditions at an appropriate temperature depending on the migratory substituent, furnishing substituted catechols in good yields. The competing reactions such as an elimination of a substituent or α-ketol rearrangement were minimized by controlling the reaction temperature.

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Synthesis of 1H-2-Benzopyran-5,8-dione Skeleton through a Cascade Reaction between Benzoquinone and β-Ketoester

Nakahara M., Ohtsu H., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

Chemistry Letters 51 ( 4 ) 356 - 359 2022.04

Research paper (scientific journal), Accepted

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The 1H-2-benzopyran-5,8-dione structure was synthesized by a cascade reaction through Michael addition, elimination of HBr, and O-alkylation between a dibromobenzoquinone derivative and β-ketoesters under basic conditions. The reaction using potassium carbonate and 18-crown-6 in THF was the best condition, giving 1H-2-benzopyran-5,8-dione derivatives in good yields. The UV-vis absorption spectrum and cyclic voltammogram of the synthesized 1H-2-benzopyran-5,8-dione derivative were measured, clarifying the photophysical and redox properties.

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Isorhamnetin promotes 53BP1 recruitment through the enhancement of ATM phosphorylation and protects mice from radiation gastrointestinal syndrome

Nishiyama Y., Morita A., Tatsuta S., Kanamaru M., Sakaue M., Ueda K., Shono M., Fujita R., Wang B., Hosoi Y., Aoki S., Sugai T.

Genes (Genes)  12 ( 10 )  2021.10

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Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary reg-ulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, iso-rhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irra-diation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair pro-cess, which is presumably associated with the suppressive effect against GI syndrome.

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Metal-free thermal organocatalytic pinacol coupling of arylaldehydes using an isonicotinate catalyst with bis(pinacolato)diboron

Yasui M., Hanaya K., Suugai T., Higashibayashi S.

RSC Advanced (RSC Advances)  2021 ( 11 ) 24652 - 24655 2021.08

Accepted

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The metal-free thermal organocatalytic pinacol coupling of arylaldehydes has been developed. The intermolecular coupling of arylaldehydes catalyzed by t-butyl isonicotinate with bis(pinacolato)diboron as the co-reducing agent afforded 1,2-diphenylethane-1,2-diols. This reaction was also applicable to the intramolecular coupling of 1,10-biphenyl-2,20-dicarbaldehydes to afford 9,10-dihydrophenanthrene-9,10-diols. Various functional groups were tolerated under this coupling condition.

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A Concise Total Synthesis of Dehydroantofine and Its Antimalarial Activity against Chloroquine-Resistant Plasmodium falciparum

Yamasaki N., Iwasaki I., Sakumi K., Hokari R., Ishiyama A., Iwatsuki M., Nakahara M., Higashibayashi S., Sugai T., Imagawa H., Kubo M., Fukuyama Y., Ōmura S., Yamamoto H.

Chemistry - A European Journal (Chemistry - A European Journal)  27 ( 17 ) 5555 - 5563 2021.03

Accepted,  ISSN  09476539

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The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels–Alder reaction of easily accessible 3,5-dichloro-2H-1,4-oxazin-2-one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine-resistant Plasmodium falciparum.

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Chemo-enzymatic Semisynthesis of Caffeic Acid β-Phenethyl Ester, an Antioxidative Component in Propolis, from Raw Coffee Beans Extract

R. Hashimoto, H. Iai, R. Fujita, K. Hanaya, S. Higashibayashi, H. Inoue, T. Sugai

Bioscience, Biotechnology and Biochemistry 85   476 - 480 2021.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

Nickel(II)-Mediated C−S Cross-Coupling Between Thiols and ortho-Substituted Arylboronic Acid

Hanaya K., Ohtsu H., Kawano M., Higashibayashi S., Sugai T.

Asian Journal of Organic Chemistry (Asian Journal of Organic Chemistry)  10 ( 3 ) 582 - 587 2021.03

Accepted,  ISSN  21935807

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Herein, we report a C−S cross-coupling reaction between alkyl thiols or aryl thiols and ortho-substituted arylboronic acids that proceeds in the presence of an inexpensive and ligand-free NiCl2 ⋅ 6H2O salt and N-methylmorpholine, a weak base, at 25 °C in air. The presence of coordinating and electron-withdrawing groups at the ortho-position of the arylboronic acids played a crucial role in determining the efficiency of the reaction. X-ray crystallographic analysis revealed that the [NiCl2(DMF)2(H2O)2] complex was formed in-situ. The complex is an excellent precursor of the active nickel species. The reaction offers an extremely mild and operationally convenient method to access a wide variety of alkyl aryl sulfides and diaryl sulfides without using expensive transition metals, such as palladium, gold, and rhodium, and specialized and expensive ligands.

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Analysis of Interconversion between Atropisomers of Chiral Substituted 9,9’-Bicarbazole

T. Kobayashi, F. Ishiwari, T. Fukushima, K. Hanaya, T. Sugai, S. Hibashibayashi

Eur. J. Org. Chem.    449 - 451 2021.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

Selective capture and noninvasive release of cells using a thermoresponsive polymer brush with affinity peptides

K. Nagase, M. Shimura, R. Shimane, K. Hanaya, S. Yamada, A. Mizutani-Akimoto, T. Sugai, H. Kanazawa

Biomater. Sci. (Biomaterials Science)  9 ( 3 ) 663 - 674 2021.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  20474830

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Tissue engineering and cell transplantation therapy have become promising therapies for intractable diseases. These approaches require cell separation technology without cell modification. Accordingly, in this study, we developed a novel cell separation method using a thermoresponsive block copolymer brush with an affinity peptide. A block copolymer brush with bottom poly(2-hydroxyethyl methacrylate [HEMA]-co-propargyl acrylate) and top poly(N-isopropylacrylamide-co-HEMA) segments was prepared through two steps of atom transfer radical polymerization. Then, cell affinity peptides were conjugated to the bottom segment of the copolymer brush through a click reaction. Using cRGD as a cell-Affinity peptide, enhancement of cell adhesion with rapid adhesion on the copolymer brush was observed at 37 °C, whereas the copolymer brush without cRGD did not exhibit cell adhesion. Temperature-modulated cell adhesion and detachment were performed with a relatively long upper segment because the affinity between peptides and cells was modulated by the swelling and shrinking of the upper thermoresponsive segment. Selective endothelial cell adhesion was performed at 37 °C using GGGREDV as an affinity peptide. Smooth muscle cells and fibroblasts did not adhere to the copolymer brush. Adhered human umbilical vein endothelial cells (HUVECs) were successfully recovered by reducing the temperature to 20 °C. Based on the properties of the copolymer brush, HUVECs could be purified using a mixture of cells simply by changing the temperature. These results demonstrated that the prepared copolymer brush with cell affinity peptides could be a useful cell separation tool because the cells could be separated with specificity and without cell modification using a simple procedure.

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Semisynthesis of prunetin, a bioactive O-methylated isoflavone from naringenin, by the sequential deacetylation of chalcone intermediates and oxidative rearrangement

T. Sugai, K. Hanaya, S. Higashibayashi

Bioscience, Biotechnology and Biochemistry 85   143 - 147 2021.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

Theoretical Analysis ofHeterocyclic [4+2] Cycloaddition between Pyridinium Ion and Enol Ether

M. Nakahara, K. Hanaya, T. Sugai, S. Hibashibayashi

Chemistry Open (ChemistryOpen)  10 ( 6 ) 627 - 629 2020.12

Research paper (scientific journal), Joint Work, Accepted

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Dearomative heterocyclic [4+2] cycloaddition between the N-(2,4-dinitrophenyl)pyridinium ion of nicotinamide and an enol ether was analyzed by Density Functional Theory (DFT) calculations. The calculation revealed that the reaction undergoes stepwise bond formation rather than occurring in a concerted manner. The experimental products were found to be both kinetically and thermodynamically favored. The calculated transition states and intermediate suggested that the high diastereoselectivity is derived from the electrostatic interaction between the 2-nitro group of the pyridinium ion and the hydrogen of the enol ether.

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Improved preparation of vitexin from hot water extract of Basella alba, the commercially available vegetable Malabar spinach (“Tsurumurasaki” in Japanese) and the application to semisynthesis of chafuroside B

Kurahayashi K., Hanaya K., Higashibayashi S., Sugai T.

Bioscience, Biotechnology and Biochemistry 84   1554 - 1559 2020.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

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Hot water extraction of D-arabinofuranosylvitexin from the raw leaves of commercially available Basella alba “Tsurumurasaki” and subsequent acidic hydrolysis was improved to be a procedure using a high-pressure steam sterilizer to afford vitexin. The amount was estimated to be 14.1 mg from 1 g of dry weight of the raw leaves, whose recovery was calculated to be 95% based on the estimated content of D-arabinofuranosylvitexin in B. alba raw leaves. The product was dehydratively cyclized between hydroxy groups on the carbohydrate and flavone skeletons under modified Mitsunobu reaction conditions in N,N-dimethylformamide to give chafuroside B, which is known to be a bioactive Oolong tea polyphenol. Through these transformations, 10.2 mg of chafuroside B could be semisynthesized from 1 g of dry weight of the raw leaves, and the efficiency was improved compared to that from the extraction from Oolong tea (3.4 μg from 1 g of dry weight).

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Comprehensive semisyntheses of catathelasmols C, D, and E from D-glutamic acid, utilizing lipase-catalyzed site-selective reactions on intermediates

Hashiba R., Hashimoto R., Nishiguchi M., Kobayashi T., Hanaya K., Higashibayashi S., Sugai T.

Bioscience, Biotechnology and Biochemistry 84   1339 - 1344 2020.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

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Catathelasmols C, D, and E, which had been isolated from Catathelasma imperiale as inhibitors for 11-hydroxysteroid dehydrogenases, were comprehensively semisynthesized from commercially available D-glutamic acid. The key synthetic intermediate, (R)-pentane-1,2,5-triol, was site-selectively acetylated by treatment with vinyl acetate and Candida antarctica lipase B (Novozym 435) in tetrahydrofuran (THF) at 25°C to furnish 1,5-diacetate (catathelasmol E, quantitative). The acetylation occurred site-selectively on the primary alcohols at the C-1 and C-5 positions over the secondary alcohol at the C-2 position. Dichromic acid oxidation provided 2-oxopentane-1,5-diyl diacetate (catathelasmol C, 78%). Burkholderia cepacia lipase-catalyzed transesterification with methanol in THF at–5°C proceeded preferentially on the acetate at C-1 located adjacent to the C-2 carbonyl group over the other terminal acetate at the C-5 position. 5-Hydroxy-4-oxopentyl acetate (catathelasmol D) was obtained in 53% yield.

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Stepwise approach for sterically hindered C<inf>sp³</inf>-C<inf>sp³</inf> bond formation by dehydrogenative: O -alkylation and Lewis acid-catalyzed [1,3]-rearrangement towards the arylalkylcyclopentane skeleton of sesquiterpenes

Fujitani B., Hanaya K., Sugai T., Higashibayashi S.

Chemical Communications (Chemical Communications)  56 ( 25 ) 3621 - 3624 2020.03

Research paper (scientific journal), Accepted,  ISSN  13597345

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This journal is © The Royal Society of Chemistry. A stepwise dehydrogenative cross-coupling method was developed for the formation of sterically hindered Csp3-Csp3 bonds. Intramolecular dehydrogenative O-alkylation of a β-ketoester by 2,3-dichloro-5,6-dicyano-p-benzoquinone to form an oxolane followed by Lewis acid-catalyzed [1,3]-rearrangement furnished the sesquiterpene arylmethylcyclopentane skeleton. The formal syntheses of herbertane-type β-herbertenol, cuparane-type enokipodins A and B were also achieved.

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Syntheses of Indirubins by Aldol Condensation of Isatins with Indoxyl Anion Generated in situ by Lipase-Catalyzed Deacetylation of Indoxyl Acetate

Sugai, T.; Hanaya K., Higashibayashi S.

Heterocycles (Heterocycles)  100 ( 1 ) 129 - 136 2019.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03855414

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© 2019 The Japan Institute of Heterocyclic Chemistry. The syntheses of indirubin (76% yield), 6-bromoindirubin (82% yield), and 6-bromoindirubin-3′-oxime (78% yield in two steps) were achieved via the lipase-triggered aldol condensation between isatins and an indoxyl anion in tetrahydrofuran under anhydrous and anaerobic conditions as the key step. The aldol donor was generated in situ by Burkholderia cepacia lipase (Amano PS-IM)-catalyzed deacetylation of commercially available and stable indoxyl acetate in the presence of triethylamine and with 2-propanol as the transesterification reagent. The scale-up of the presently developed reactions is easier than that in the previously reported chemical aldol condensations, because of the simplicity of the isolation procedure and suppression of the oxidative byproduct formation from indoxyl acetate.

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Chemoenzymatic Synthesis of Hydroxytyrosol Monoesters and Their Suppression Effect on Nitric Oxide Production Stimulated by Lipopolysaccharides

A. Sakakura, M. Pauze, A. Namiki, M. Funakoshi-Tago, H. Tamura, K. Hanaya, S. Higashibayashi, T. Sugai

Biosci. Biotechnol. Biochem. (Bioscience, Biotechnology and Biochemistry)  83 ( 2 ) 185 - 191 2019.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

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© 2018 Japan Society for Bioscience, Biotechnology, and Agrochemistry. Fatty acid monoesters of hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol] were synthesized in two steps from tyrosol (4-hydroxyphenylethanol) by successive Candida antarctica lipase B-catalyzed chemoselective acylation on the primary aliphatic hydroxy group over phenolic hydroxy group in tyrosol, and 2-iodoxybenzoic acid (IBX)-mediated hydroxylation adjacent to the remaining free phenolic hydroxy group. Examination of their suppression effects on nitric oxide production stimulated by lipopolysaccharides in RAW264.7 cells showed that hydroxytyrosol butyrate exhibited the highest inhibition (IC 50 7.0 μM) among the tested compounds.

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Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance

Tsunekawa R., Katayama K., Hanaya K., Higashibayashi S., Sugimoto Y., Sugai T.

ChemBioChem (ChemBioChem)  20 ( 2 ) 210 - 220 2019.01

ISSN  14394227

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© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI 50 ). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI 50 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI 50 18 nm). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI 50 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.

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Preparation of Menisdaurigenin and Related Compounds

R. Shirakawa, S. Ishikawa; M. Takahashi, Y. Ueno, Y. Uekusa, Y. Narukawa. T. Sugai, F. Kiuchi

J. Nat. Med. (Journal of Natural Medicines)  73 ( 1 ) 236 - 243 2019.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  13403443

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© 2018, The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature. Menisdaurin (1), a cyano glucoside, was first isolated in 1978 from Menispermum dauricum (Menispermaceae) and named after the plant. It has been also isolated from several plant sources. The stereochemistry of the aglycone part was first reported as (Z,4R,6S)-enantiomer of (4,6-dihydroxy-2-cyclohexen-1-ylidene)acetonitrile based on the CD spectrum of menisdaurilide (2), the α,β-unsaturated γ-lactone obtained by an acid hydrolysis of menisdaurin. Later, the absolute stereochemistry was revised as (Z,4S,6R) by X-ray crystal analysis of 1 isolated from Saniculiphyllum guangxiens. The aglycone part of menisdaurin (1) has not been obtained from 1, because an acid hydrolysis of 1 gave menisdaurilide (2), and enzymatic hydrolysis with emulsin did not give the aglycone. On the other hand, a compound named coculauril (3) was isolated from Cocculus lauriforius. This compound has the same planner structure corresponding to the aglycone of 1, but the stereochemistry was reported to be (E,4R,6S). Here, we confirmed the absolute stereochemistry of 1 by Mosher’s method to be (Z,4S,6R), and prepared the aglycone of 1, i.e., menisdaurigenin (4) by an enzymatic hydrolysis of 1. We also revealed that 4 is a different compound from 3 and unstable in water and MeOH.

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Dearomative Oxidative Rearrangement of [3]Cyclo-1,8-carbazolylene

M. Yasui, H. Ohtsu, M. Kawano, K. Hanaya, T. Sugai, S. Higashibayashi

Chem. Lett. (Chemistry Letters)  47 ( 11 ) 1357 - 1359 2018.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03667022

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© 2018 The Chemical Society of Japan. [3]Cyclo-1,8-carbazolylene was found to undergo oxidative rearrangement by oxidation with 2,3-dichloro-5,6-dicyano-pbenzoquinone, giving a 9a-substituted carbazol-1-one derivative. This is the first example of a dearomative oxidative rearrangement of a carbazole or aniline derivative. The geometrical and electronic structures were elucidated by X-ray analysis, UV-vis absorption spectroscopy, and DFT calculations.

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Synthesis of Trilobatin from Naringin via Prunin as the Key Intermediate: Acidic Hydrolysis of the α-Rhamnosidic Linkage in Naringin under Improved Conditions

K. Kurahayashi, K. Hanaya, S. Higashibayashi, T. Sugai

Biosci. Biotechnol. Biochem. (Bioscience, Biotechnology and Biochemistry)  82 ( 9 ) 1463 - 1467 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

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© 2018 Japan Society for Bioscience, Biotechnology, and Agrochemistry Trilobatin [4-(β-D-glucopyranosyloxy)-2,4”,6-trihydroxydihydrochalcone] was synthesized from commercially available naringin in three steps with an overall yield of 30%. The key step was the acid-catalyzed site-selective hydrolysis of terminal α-rhamnopyranosidic linkage in neohesperidose involved in naringin under controlled conditions, by applying a high-pressure steam sterilizer.

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Synthesis of oroxylin A starting from naturally abundant baicalin

R. Fujita, K. Hanaya, S. Higashibayashi, T. Sugai

Heterocycles (Heterocycles)  97 ( 2 ) 1165 - 1174 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03855414

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© 2018 The Japan Institute of Heterocyclic Chemistry – A new approach to oroxylin A, a monomethylated trihydroxyflavone, is described. The starting material was baicalin, a representative naturally abundant flavonoid glucuronide. First, conditions for the cleavage of the glycosidic bond were established, using a mixture of water and conc. sulfuric acid (5:2) at 121 °C for 40 min. The hydrolysis was performed in a high-pressure steam sterilizer so that the temperature and reaction time were precisely controlled. Subsequent acetylation of the crude material furnished baicalein 6,7-diacetate on a preparative scale and in a reproducible manner. Next, the C-7 position was protected site-selectively with a methoxymethyl (MOM) group, taking advantage of an unexpected sequential migration of the two acetyl groups among the C-5, C-6, and C-7 positions under basic conditions. The removal of the two remaining acetyl groups followed by site-selective methylation of the C-6 position furnished 5-hydroxy-6-methoxy-7-methoxymethoxyflavone (oroxylin A C-7 MOM ether). Finally, by the deprotection of the MOM ether, oroxylin A was obtained in 6 total steps and 62% overall yield from baicalin.

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Site-selective synthesis of acacetin and genkwanin through lipase-catalyzed deacetylation of apigenin 5,7-diacetate and subsequent methylation

Fujita R., Mandal S., Hanaya K., Shoji M., Higashibayashi S., Sugai T.

Heterocycles (Heterocycles)  99 ( 1 ) 638 - 648 2018.08

Research paper (scientific journal), Accepted,  ISSN  03855414

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© 2019 The Japan Institute of Heterocyclic Chemistry. Candida antarctica lipase B-catalyzed deacetylation proceeded with high site-selectivity on the C-4′ acetyl group in apigenin triacetate to give apigenin 5,7-diacetate. Methylation of the liberated hydroxy group with the combination of trimethyloxonium tetrafluoroborate (Meerwein reagent) and 1,8-bis(dimethylamino)naphthalene (proton sponge) in CH2Cl2 proceeded in a quantitative manner to give the product methylated at the C-4′ hydroxy group (acacetin 5,7-diacetate). Even with the same precursor, a different methylation product at the C-7 hydroxy group (genkwanin 4′,5-diacetate) was obtained in 86% yield by applying iodomethane and Cs2CO3 in dimethyl sulfoxide (DMSO). The methylated products were deprotected to form acacetin and genkwanin. We inferred that the latter unexpected methylation was ascribable to the intermolecular migration of an acetyl group from C-7 to C-4′. DFT calculations indicated that the C-7 phenoxide ion was 12.6 kJ/mol more stable than the initially formed C-4′ phenoxide ion.

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Synthesis and Properties of Hydrazine-Embedded Biphenothiazines and Application of Hydrazine-Embedded Heterocyclic Compounds to Fluorescence Cell Imaging

Y. Shindo, S. Nomura, Y. Saikawa, M. Nakata, K. Tanaka, K. Hanaya, T. Sugai, S. Higashibayashi

Asian J. Org. Chem. (Asian Journal of Organic Chemistry)  7 ( 9 ) 1797 - 1801 2018.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  21935807

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© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Hydrazine-embedded unsubstituted butterfly-shaped biphenothiazine and its sulfoxides were synthesized by dimerization of 1,9-dibromophenothiazine, which was prepared by realizing selective debromination at the 3,7-positions of 1,3,7,9-tetrabromophenothiazine. cis/trans-Biphenothiazine sulfoxide was selectively prepared by changing the oxidation temperature to control the inversion rate of the butterfly shape of the intermediate. Their butterfly-shapes, conformations, photophysical properties (UV-vis absorption, fluorescence), and redox properties were elucidated by X-ray analysis, DFT calculations, spectral and electrochemical measurements. Fluorescent hydrazine-embedded biphenothiazine sulfoxides and bicarbazoles were applied to cell imaging of HeLa cells. The bicarbazoles exhibited high fluorescence signals in the cells with low toxicity.

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Lipase-catalyzed site-selective deacetylation of sterically hindered naphthohydroquinone diacetate and its application to the synthesis of a heterocyclic natural product

Hashimoto R., Sakakura A., Hanaya K., Higashibayashi S., Sugai T.

Heterocycles (Heterocycles)  99 ( 1 ) 625 - 632 2018.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03855414

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© 2019 The Japan Institute of Heterocyclic Chemistry. Lipase-catalyzed site-selective deacetylation of 2,5-dimethylnaphthalene-l,4-diol diacetate was examined. With Candida antarctica lipase B, the suppressing effect of a methyl substituent at the peri-position of the a-naphthyl ester over that at the ortho-position was significant. This site-selectivity was in contrast to that of chemical hydrolysis reported to date. From the resulting monoacetate, mansonone F, a physiologically active heterocyclic orthoquinone, was synthesized in 38% yield in as few as three steps.

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Effect of hesperetin derivatives on the development of selenite-induced cataracts in rats

Nakazawa Y., Pauze M., Fukuyama K., Nagai N., Funakoshi-Tago M., Sugai T., Tamura H.

Molecular Medicine Reports (Molecular Medicine Reports)  18 ( 1 ) 1043 - 1050 2018.07

ISSN  17912997

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Copyright © Spandidos Publications 2017. All rights reserved. Cataracts are a major cause of blindness worldwide. As anti-cataract pharmaceutical therapies require long-term treatment, identifying anti-cataract compounds that are ubiquitous in the human diet, have no adverse effects and are affordable, is of paramount importance. The present study focused on hesperetin and its derived compounds, hesperetin stearic acid ester (Hes-S) and hesperetin oleic acid ester (Hes-O), in order to investigate their therapeutic potential to treat cataracts in a selenite animal model. Thirteen-day-old Sprague Dawley rats were divided into 12 groups. Animals in groups 1 and 7 were subcutaneously injected with vehicle, those in groups 2 and 8 were administered hesperetin, those in groups 3 and 9 received stearic acid, those in groups 4 and 10 were injected with oleic acid, those in groups 5 and 11 were administered Hes-S, and those in groups 6 and 12 received Hes-O (10 nmol/kg body weight on days 0, 1 and 2). Animals in groups 7 to 12 were treated with sodium selenite (20 µmol/kg body weight given 4 h following the test compound treatment on day 0) to induce cataract. On day 6, rats had less severe central opacities and lower stage cataracts than rats in the selenite treatment-only control groups. The levels of glutathione (GSH) and ascorbic acid (AsA) in lenses with selenite-induced cataracts declined to one-third of that of controls, and the reduction in GSH and AsA levels was rescued following hesperetin, Hes-S or Hes-O treatment, with concentrations remaining to 70-80% of that of controls. However, there were no changes in the plasma levels of GSH and AsA following treatments. Administration of either hesperetin or hesperetin-derived compounds prevented the reduction of chaperone activity in the lens, and rats treated with Hes-S or Hes-O treatment had significantly greater chaperone activity than hesperetin-treated rats. Collectively, these results suggested that hesperetin and hesperetin-derived compounds may be novel drug compounds that have the potential to prevent or delay the onset of cataracts.

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Hydroxytyrosol butyrate inhibits 6-OHDA-induced apoptosis through activation of the Nrf2/HO-1 axis in SH-SY5Y cells

M. Funakoshi-Tago, T. Sakata, S. Fujiwara, A. Sakakura, T. Sugai, K. Tago, and H. Tamura

Eur. J. Pharmacol. (European Journal of Pharmacology)  834   246 - 256 2018.05

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00142999

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© 2018 Elsevier B.V. Hydroxytyrosol (HT) is a polyphenol contained in olives and exhibits antioxidant activity. We herein investigated the effects of HT and its derivatives, hydroxytyrosol acetate (HT-A) and hydroxytyrosol butyrate (HT-B), on the protection of neuronal cells against apoptosis induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). The pretreatment of SH-SY5Y cells with HT-B, but not HT or HT-A significantly reduced the 6-OHDA-induced generation of reactive oxygen species, activation of caspase-3, and subsequent cell death. HT-B also induced the protein expression of the transcription factor, NF-E2-related factor-2 (Nrf2) and its transcriptional activation, resulting in the up-regulated expression of heme oxygenase-1 (HO-1), which conferred neuroprotection against 6-OHDA-induced oxidative damage. Furthermore, three cysteine residues, Cys151, Cys273, and Cys288 in Kelch-like ECH-associated protein 1 (Keap1) were necessary for the HT-B-induced activation of Nrf2. Collectively, the present results demonstrated that HT-B, harboring higher fat solubility than HT and HT-A, effectively elicited adaptive responses to oxidative stress by activating the Nrf2/HO-1 axis in neuronal cells.

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Synthesis of enantiomerically enriched drug precursors and an insect pheromone via reduction of ketones using commercially available carbonyl reductase screening kit “Chiralscreen® OH”

T. Nagai, S. Sakurai, N. Natori, M. Hataoka, T. Kinoshita, H. Inoue, K. Hanaya, M. Shoji, T. Sugai

Bioorg. Med. Chem. (Bioorganic and Medicinal Chemistry)  26 ( 7 ) 1304 - 1313 2018.04

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09680896

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© 2017 Elsevier Ltd Commercially available “Chiralscreen® OH” starter kit containing five types of carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction of several aromatic and aliphatic ketones to obtain enantiomerically enriched drug precursors and an insect pheromone. Almost stereochemically pure secondary alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)-rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked well with ketones containing at least one non-bulky substituent at the carbonyl group. The diverse stereochemical preference of the above five carbonyl reductases was clarified.

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Synthesis of 3β-tert-butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and reductive nucleophilic attack on a branched aliphatic aldehyde

T. Nagai, K. Hanaya, S. Higashibayashi, M. Shoji, T. Sugai

Chem. Pharm. Bull. (Chemical and Pharmaceutical Bulletin)  64 ( 3 ) 334 - 338 2018.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00092363

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© 2018 The Pharmaceutical Society of Japan. 3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene, which has a double bond between C-9 and C-11 and a phenylsulfenyl group on the terminus of the side chain, is a potential synthetic intermediate for steroids with 9,11-unsaturation or 9,11-seco skeletons. We describe here the synthesis of the title compound from 17-ethylenedioxy-3-acetoxyandrosta-3,5-dien-11-one. The introduction of an ethylene unit to 3β-tert-butyldimethylsiloxyandrosta-5,9(11)-dien-17-one by the action of ethyltriphenylphosphonium bromide under basic conditions resulted in an inseparable mixture of two stereoisomeric products (5 : 1). However, in the subsequent step, only the (Z)-isomer was susceptible to the Lewis acid-catalyzed ene reaction with formaldehyde, giving a stereochemically pure product with the desired configuration. Within three steps, the ene-product was derivatized to the title compound, with a total yield of 53% over seven steps. Reductive terminal anion formation by treatment with lithium di-tert-butylbiphenyl (LiDBB) and subsequent nucleophilic attack on a branched aliphatic aldehyde was demonstrated, with an eye toward the introduction of side chains, especially for steroids with oxygen functionality at C-23.

Formal total synthesis of (−)-hamigeran B from a chemo-enzymatically prepared building block with quaternary chiral center

Kuwata K., Fujita R., Hanaya K., Higashibayashi S., Sugai T.

Tetrahedron (Tetrahedron)  74 ( 7 ) 740 - 745 2018.02

ISSN  00404020

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© 2017 Elsevier Ltd A formal total synthesis of (−)-hamigeran B was achieved in 17 steps from commercially available ethyl 2-oxocyclopentanecarboxylate. Carbonyl reductase-catalyzed asymmetric reduction and the subsequent chemical transformations furnished an enantiomerically pure synthetic intermediate, (R)-5-formyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate. Suzuki-Miyaura coupling with Gao's arylboronate [2-(2-formyl-3-methoxy-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane], under PdCl2(dppf)•CH2Cl2 catalysis, and the subsequent cyclization by way of intramolecular reductive SmI2-mediated 1,2-diol formation provided a tricyclic skeleton with a tetrasubstituted double bond between C-1 and C-9b. Upon hydrogenation of this double bond, the proper stereochemistry of the remaining chiral centers was established. Exclusive addition of the hydrogen atom from the β-face occurred, owing to the shielding of the α-face with a bulky TBS protective group on the C-4 alcohol. The hydrogenation products were transformed into Clive's synthetic precursor for (−)-hamigeran B.

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Formal synthesis of englerin A utilizing regio- and diastereoselective [4 + 3] cycloaddition

S. Hagihara, K. Hanaya, T. Sugai, M. Shoji

J. Antibiot. (Journal of Antibiotics)  71 ( 2 ) 257 - 262 2018.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00218820

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© 2018 Japan Antibiotics Research Association All rights reserved. Englerin A, a guaiane sesquiterpene isolated from Phyllanthus engleri, showed highly potent and selective growth inhibitory activities against renal cancer cell lines. We synthesized the key tricyclic intermediate from commercially available 2,2-dimethyl-1,3-dioxan-5-one via regio- and diastereoselective [4+3] cycloaddition between the formyl enol silyl ether and the disubstituted furan, in 4.8% total yield over 10 steps.

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Synthesis of fisetin and 2′,4′,6′-trihydroxydihyrochalcone 4′-O-β-neohesperidoside based on site-selective deacetylation and deoxygenation

Tsunekawa R., Hanaya K., Higashibayashi S., Sugai T.

Bioscience, Biotechnology and Biochemistry (Bioscience, Biotechnology and Biochemistry)  82 ( 8 ) 1316 - 1322 2018

ISSN  09168451

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© 2018 Japan society for Bioscience, Biotechnology, and Agrochemistry. Fisetin and 2′,4′,6′-trihydroxydihyrochalcone 4′-O-β-neohesperidoside were synthesized from commercially available quercetin and naringin in five steps. The key steps are site-selective deacetylation and subsequent deoxygenation. The target molecules were obtained in 37% and 23% yields from the starting materials, respectively.

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Chemoenzymatic approaches to the synthesis of the (1S,2R)-isomer of benzyl 2-hydroxycyclohexanecarboxylate

R. Tsunekawa, K. Hanaya, S. Higashibayashi, M. Shoji, T. Sugai

Mol. Catal. (Molecular Catalysis)  444   84 - 89 2017.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  24688231

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© 2017 Elsevier B.V. We examined ten strains of cultured whole-cell yeasts for the asymmetric reduction of commercially available ethyl 2-oxocyclohexanecarboxylate, and found that the (1S,2S)-stereoisomer of ethyl 2-hydroxycyclohexanecarboxylate was the major stereoisomer produced by Williopsis californica JCM 3600. The ethyl group of the ester was then substituted with a benzyl group with low volatility and increased hydrophobicity to facilitate the isolation of the expected product. Incubation with W. californica furnished benzyl (1S,2S)-2-hydroxycyclohexanecarboxylate (>99.9% ee) in 51.0% yield together with its (1R,2S)-isomer (>99.9% ee) in 35.4% yield. Upon treatment of the same substrate bearing the benzyl ester with a screening kit of purified overexpressed carbonyl reductases (Daicel Chiralscreen® OH), two enzymes (E031, E078) furnished the (1R,2S)-isomer as the major product. With another enzyme (E007), the (1S,2R)-isomer was obtained, but its ee was very low (25.6%). The highly enantiomerically enriched (1S,2S)-isomer obtained by W. californica was transformed to the (1S,2R)-isomer (>99.9% ee), whose availability until now has been low, in 43.3% yield over two steps involving tosylation and subsequent inversive attack with tetrabutylammonium nitrite.

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Construction of 2,6,9,11-tetraoxatricyclo[6.2.1.03,8]undecane containing 4-keto-D-glucose skeleton

B. Fujitani, K. Hanaya, S. Higashibayashi, M. Shoji, T. Sugai

Tetrahedron 73   7217 - 7222 2017.11

Research paper (scientific journal), Joint Work, Accepted

A novel phenylphthalimide derivative, pegylated TC11, improves pharmacokinetic properties and induces apoptosis of high-risk myeloma cells via G2/M cell-cycle arrest

S. Aida, M. Hozumi, D. Ichikawa, K. Iida, Y. Yonemura, N. Tabata, T. Yamada, M. Matsushita, T. Sugai, H. Yanagawa, Y. Hattori

Biochem. Biophys. Res. Commun. 493   514 - 520 2017.11

Research paper (scientific journal), Joint Work, Accepted

Synthesis of the 1,2-seco fusicoccane diterpene skeleton by Stille coupling reaction between the highly functionalized A and C ring segments of cotylenin A

K. Kuwata, K. Hanaya, S. Higashibayashi, T. Sugai, M. Shoji

Tetrahedron 73   6039 - 6045 2017.09

Research paper (scientific journal), Joint Work, Accepted

Short-step syntheses of naturally occurring polyoxygenated aromatics based on site-selective transformation

Y. Yamashita, A. Biard, K. Hanaya, M. Shoji, T. Sugai

Biosci. Biotechnol. Biochem. 65   1279 - 1284 2017.07

Research paper (scientific journal), Joint Work, Accepted

Chemo-enzymatic synthesis of (R)-5-hydroxymethyl-2-isopropyl-5-methylcyclopente-1-yl trifluoromethylsulfonate, a potential chiral building block for multicyclic terpenoid

K. Kuwata, K. Hanaya, T. Sugai, M. Shoji

Tetrahedron: Asymmetry 28   964 - 968 2017.05

Research paper (scientific journal), Joint Work, Accepted

Synthesis of trans,trans,cis-fused tetracyclic skeleton via radical domino cyclization

M. Furuta, K. Hanaya, T. Sugai, M. Shoji

Tetrahedron 73   2316 - 2322 2017.03

Research paper (scientific journal), Joint Work, Accepted

Synthesis of linezolid metabolites PNU-142300 and PNU-142586 toward the exploration of metabolite-related events

K. Hanaya, K. Matsumoto, Y. Yokoyama, J. Kizu, M. Shoji, T. Sugai

Chem. Pharm. Bull. 65   194-199 2017.02

Research paper (scientific journal), Joint Work, Accepted

Synthesis of benzyl tetra-O-acetyl-α-L-glucopyranoside from benzyl 2,3-dideoxy-β-D-erythro-hex-2-enopyranoside

H. Okazaki, Y. Ueda, K. Hanaya, M. Shoji, T. Sugai

Heterocycles 95   862 - 871 2016.11

Research paper (scientific journal), Joint Work, Accepted

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Preparation of (R)-3-hydroxy-N-methylpiperidine, a synthetic key intermediate of (R)-mepenzolate, based on the lipase-catalyzed resolution of the racemic form

Y. Yamashita, K. Hanaya, M. Shoji, and T. Sugai

Heterocycles 95   370 - 379 2016.10

Research paper (scientific journal), Joint Work, Accepted

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Simple Synthesis of Sakuranetin and Selinone via a Common Intermediate, Utilizing Complementary Regioselectivity in the Deacetylation of Naringenin Triacetate

Y. Yamashita, K. Hanaya, M. Shoji, and T. Sugai

Chem. Pharm. Bull. 64   961-965 2016.08

Research paper (scientific journal), Joint Work, Accepted

Ex Situ Enantioconvergent Approaches for the Effective Use of Undesired Isomers: Stereochemical Convergence of a Substrate with Multiple Chiral Centers and Recycling of a Decarboxylated Byproduct

Y. Yamashita, T. Kurihara, T. Horiguchi, A. Miki, M. Shoji, T. Sugai, and K. Hanaya

Synthesis 48   2191-2200 2016.04

Research paper (scientific journal), Joint Work, Accepted

Practical synthesis of the C-ring precursor of paclitaxel from 3-methoxytoluene

K. Fukaya, Y. Yamaguchi, A. Watanabe, H. Yamamoto, T. Sugai, T. Sugai, T. Sato, and N. Chida

J. Antibiot. 69   273-279 2016.02

Research paper (scientific journal), Joint Work, Accepted

Development of a Novel Sulfonate Ester-Based Prodrug Strategy

K. Hanaya, S. Yoshioka, S. Ariyasu, S. Aoki, M. Shoji, T. Sugai

Bioorg. Med. Chem. Lett 26   545-550 2016.01

Research paper (scientific journal), Joint Work, Accepted

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Synthesis of acacetin and resveratrol 3,5-di-O-β-glucopyranosideusing lipase-catalyzed regioselective deacetylation of polyphenolglycoside peracetates as the key step

S. Hanamura, K. Hanaya, M. Shoji, and T. Sugai

J. Mol. Catal. B: Enz. 128   19-26 2016.01

Research paper (scientific journal), Joint Work, Accepted

New Synthesis of Artepillin C, a Prenylated Phenol, Utilizing Lipase-catalyzed Regioselective Deacetylation as the Key Step

K. Yashiro, K. Hanaya, M. Shoji, T. Sugai

Biosci. Biotechnol. Biochem. 26   1926-1930 2015.11

Research paper (scientific journal), Joint Work, Accepted

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Recognition of the remote chiral center in lipase-catalyzed kinetic resolution of [2-methyl-2-(2′-naphthyl)-1,3-benzodioxol-4-yl]methyl acetate, the precursor of 2-methyl-2-(2′-naphthyl)-1,3-benzodioxole-4-carboxylic acid (MNB carboxylic acid)

N. Natori, K. Nakagawara, M. Shoji, T. Sugai and K. Hanaya

J. Mol. Catal. B: Enz. 109   130-135 2014.10

Research paper (scientific journal), Joint Work, Accepted

Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities

Y. Yamashita, K. Tanaka, T. Asano, N. Yamakawa, D. Kobayashi, T. Ishihara, K. Hanaya, M. Shoji, T. Sugai, M. Wada, T. Mashimo, Y. Fukunishi and T. Mizushima

Bioorg. Med. Chem. 22   3488-3497 2014.06

Research paper (scientific journal), Joint Work, Accepted

Structure–activity relationship of celecoxib and rofecoxib for the membrane permeabilizing activity

N. Yamakawa, K. Suzuki, Y. Yamashita, T. Katsu, K. Hanaya, M. Shoji, T. Sugai and T. Mizushima

Bioorg. Med. Chem. 22   2529–2534 2014.04

Research paper (scientific journal), Joint Work, Accepted

Divergent synthesis of pseudoenantiomers for ABC-ring moiety of steroids

M. Furuta, K. Hanaya, T. Sugai and M. Shoji

Tetrahedron Lett. 55   3189–3191 2014.02

Research paper (scientific journal), Joint Work, Accepted

Stereoselective Synthesis of Scyphostatin Hydrophilic Moiety

K. Kuwata, M. Suzuki, Y. Inami, K. Hanaya, T. Sugai and M. Shoji

Tetrahedron Lett. 55   2856–2858 2014.02

Research paper (scientific journal), Joint Work, Accepted

(-)-Benzyl 2,3-dideoxy-β-D-erythro-hex-2-enopyranoside

S. Ohba, H. Okazaki, Y. Ueda, K. Hanaya and T. Sugai

Acta Cryst. E69   o1811 2013.12

Research paper (scientific journal), Joint Work, Accepted

Whole-cell yeast-mediated preparation of (R)-2-chloro-1-(3-nitrophenyl)ethanol as a synthetic precursor for (R)-phenylephrine

D. Tokoshima, K. Hanaya, M. Shoji and T. Sugai

J. Mol. Catal. B: Enz. 97   95-99 2013.12

Research paper (scientific journal), Joint Work, Accepted

Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600

K. Asami, T. Machida, S. Jung, K. Hanaya, M. Shoji and T. Sugai

J. Mol. Catal. B: Enz. 97   106-109 2013.12

Research paper (scientific journal), Joint Work, Accepted

Synthesis of Methyl epi-Anhydroquinate Utilizing [2,3]-Sigmatropic Rearrangement of Iodosoalkene

S. Inomata, M. Ueda, T. Sugai and M. Shoji

Chem. Lett. 42   1273-1275 2013.10

Research paper (scientific journal), Joint Work, Accepted

An expeditious route for 2-acetamido-4-O-methyl-2-deoxy-D-mannopyranose from a Ferrier derivative of tri-O-acetyl-D-glucal, which contributes to the synthesis of laninamivir (CS-8958), a neuraminidase inhibitor

H. Okazaki, K. Hanaya, M. Shoji and T. Sugai

Tetrahedron 69   7931-7935 2013.09

Research paper (scientific journal), Joint Work, Accepted

Chemo-enzymatic enantioconvergent approach toward ethyl shikimate from ethyl 5-hydroxy-3,4-isopropylidenedioxycyclohex-1-enecarboxylate

Y. Yamashita, K. Hanaya, T. Sugai, T. Mizushima and M. Shoji

Tetrahedron 69   6527-6532 2013.08

Research paper (scientific journal), Joint Work, Accepted

Formal synthesis of (+)-madindoline A, a potent IL-6 inhibitor, utilizing enzymatic discrimination of quaternary carbon

K. Shimizu, M. Tomita, K. Fuhshuku, T. Sugai and M. Shoji

Nat. Prod. Commun. 8   897-901 2013.07

Research paper (scientific journal), Joint Work, Accepted

Synthesis of okicamelliaside, a glucoside of ellagic acid with potent anti-degranulation activity

R. Kobayashi, K. Hanaya, M. Shoji, S. Ohba and T. Sugai

Biosci. Biotechnol. Biochem. 77   810-813 2013.06

Research paper (scientific journal), Joint Work, Accepted

Chemo-enzymatic transformation of naturally abundant naringin to luteolin, a flavonoid with various biological effects

R. Kobayashi, T. Itou, K. Hanaya, M. Shoji, N. Hada and T. Sugai

J. Mol. Catal. B: Enz. 92   14-18 2013.06

Research paper (scientific journal), Joint Work, Accepted

Stereoselective construction of cis-decalin framework via radical domino cyclization

E. Suzuki, M. Ueda, S. Ohba, T. Sugai　and M. Shoji

Tetrahedron Lett. 54   1589-1592 2013.02

Research paper (scientific journal), Joint Work, Accepted

Triazoyl–phenyl linker system enhancing the aqueous solubility of a molecular probe and its efficiency in affinity labeling of a target protein for jasmonate glucoside

S. Tamura, S. Inomata, M. Ebine, T. Genji, I. Iwakura, M. Mukai, M. Shoji, T. Sugai and M. Ueda

Bioorg. Med. Chem. Lett. 23   188-193 2013.01

Research paper (scientific journal), Joint Work, Accepted

A Chemo-enzymatic Expeditious Route to Racemic Dihexanoyl (2R*,3R*,4R*)-DHMEQ (Dehydroxymethylepoxyquinomycin), the Precursor for Lipase-catalyzed Synthesis of (2S,3S,4S)-DHMEQ, a Potent NF-kB Inhibitor

R. Kobayashi, K. Hanaya, M. Shoji, K. Umezawa　and T. Sugai

Chem. Pharm. Bull. 60   1220-1223 2012.12

Research paper (scientific journal), Joint Work, Accepted

Chemo-enzymatic routes for (R)-terbutaline hydrochloride based on microbial asymmetric reduction of a-haloacetophenones

S. Taketomi, M. Asano, T. Higashi, M. Shoji　and T. Sugai

J. Mol. Catal. B: Enz. 84   83-88 2012.10

Research paper (scientific journal), Joint Work, Accepted

Reduction of acetophenones with methyl fluorines and a bulky group on the aromatic ring using microorganisms and related enzymes

C. Abe, T. Sugawara, T. Machida, T. Higashi, K. Hanaya, M. Shoji, C. Cao, T. Yamamoto, T. Matsuda and T. Sugai

J. Mol. Catal. B: Enz. 82   86-91 2012.08

Research paper (scientific journal), Joint Work, Accepted

Stereoselective approach to (2R,3S)- and (2R,3R)-1,2-(cyclohexylidenedioxy)hept-6-en-3-ol by microbial reduction

M. Furuta, M. Shoji　and T. Sugai

J. Mol. Catal. B: Enz. 82   8-11 2012.07

Research paper (scientific journal), Joint Work, Accepted

A Phthalimide derivative that Inhibits centrosomal clustering is effective on multiple myeloma

H. Shiheido, F. Terada, N. Tabata, I. Hayakawa, N. Matsumura, H. Takashima, Y. Ogawa, W, Du, T. Yamada, M. Shoji, T. Sugai, N. Doi, S. Ijima, Y. Hattori　and H. Yanagawa

Plos One 7   e38878 2012.06

Research paper (scientific journal), Joint Work, Accepted

Hybrid stereoisomers of a compact molecular probe based on a jasmonic acid glucoside: Syntheses, and biological evaluations

M. Ueda, G. Q. Yang, Y. Ishimaru, T. Itabashi, S. Tamura, H. Kiyota, S. Kuwahara, S. Inomata, M. Shoji and T. Sugai

Bioorg. Med. Chem. 20   5832-5843 2012.04

Research paper (scientific journal), Joint Work, Accepted

Examination of spacer introduction effects on stereochemical recognition of remote sterically hindered chiral center in lipase-catalyzed acylation

R. Kobayashi, H. Huang, M. Hamada, T. Higashi, M. Shoji and T. Sugai

J. Mol. Catal. B: Enz. 81   52-57 2012.04

Research paper (scientific journal), Joint Work, Accepted

　View Summary

リパーゼを用いた遠隔不斉中心認識について、新しい知見を得た。

Chemoenzymatic synthesis of (2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ), a new activator of antioxidant transcription factor Nrf2

Y. Niitsu, M. Hakamata, Y. Goto, T. Higashi, M. Shoji, T. Sugai and K Umezawa

Org. Biomol. Chem. 9   4635-4641 2011.04

Research paper (scientific journal), Joint Work, Accepted

　View Summary

(2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ)を、新しい基質設計に基づきリパーゼを用いた速度論的光学分割により調製、Nrf2活性化を促進することを見出した。

Chemo-enzymatic Synthesis of Both Enantiomers of 2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic (TBMB) Acid

T. Higashi, C. Abe, K. Ninomiya, T. Machida, N. Chishima, S. Taketomi, M. Furuta, Y. Komaki, Y. Senba, T. Tokuda, M. Shoji and T. Sugai

Adv. Synth. Catal. 352   2549-2558 2010.12

Research paper (scientific journal), Joint Work, Accepted

　View Summary

TBMBカルボン酸を、トリフルオロメチルケトンの微生物不斉還元、およびリパーゼを用いた速度論的光学分割を相乗的に組み合わせ、純粋な両鏡像体として得る方法を見出した。

Lipase-catalyzed enantio- and regioselective transformation of 3-epi-shikimic acid derivatives as the key step for the entry of polyoxygenated carbacycles

M. Hamada, T. Higashi, M. Shoji, K. Umezawa, T. Sugai

J. Mol. Catal. B: Enz. 67   78-84 2010.09

Research paper (scientific journal), Joint Work, Accepted

　View Summary

フランとアクリル酸のDiels-Alder反応、ヨードラクトン化、位置選択的環化を経て得られるラセミ体のシクロヘキセントリオールを、リパーゼを用いエステル交換することにより速度論的光学分割した。

The scope and limitation on the regio- and enantioselective hydrolysis of aliphatic epoxides by Bacillus subtilis epoxide hydrolase, and exploration towards chirally differentiated tris(hydroxymethyl)methanol

K. Shimizu, M. Sakamoto, M. Hamada, T. Higashi, T. Sugai, M. Shoji

Tetrahedron: Asymmetry 21   2043-2049 2010.07

Research paper (scientific journal), Joint Work, Accepted

　View Summary

Bacillus subtilis由来のエポキシドヒドロラーゼの基質特異性を検討し、新しい第三級アルコールキラルシントンの調製法を開拓した。

Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomycin (DHMEQ), a potent inhibitor on NF-κB

M. Hamada, Y. Niitsu, C. Hiraoka, I. Kozawa, T. Higashi, M. Shoji, K. Umezawa, T. Sugai

Tetrahedron 66   7083-7087 2010.07

Research paper (scientific journal), Joint Work, Accepted

　View Summary

エノンの不斉エポキシ化、最終物のリパーゼによる速度論的分割を相乗的に活用した、DHMEQの新しい不斉合成ルートを確立した。

New chemo-enzymatic route toward N-acetylneuraminic acid derivatives with alkyl groups at C-7 hydroxyl group

J. Calveras, Y. Nagai, I. Sultana, Y. Ueda, T. Higashi, M. Shoji, T. Sugai

Tetrahedron 66   4284-4291 2010.04

Research paper (scientific journal), Joint Work, Accepted

　View Summary

トリアセチル-D-グルカールをリパーゼで位置選択的に脱保護、カルバミル誘導体のRh環化を活用し、マンノサミンやシアル酸類の効率よい合成を達成した。

Elaboration on the access to (S)-4-(4-methylbenzyl)oxy-3-hydroxybutanenitrile, a key intermediate for statins, by combining the kinetic resolution of racemate and the recycle of undesired enantiomer

M. Sakamoto, M. Hamada, T. Higashi, M. Shoji, T. Sugai

J. Mol. Catal. B: Enz. 64   96-100 2010.02

Research paper (scientific journal), Joint Work, Accepted

　View Summary

ラセミ体のリパーゼによるエステル交換、fast isomerの酸化－微生物還元によるリサイクルを統合し、スタチン中間体の効率良い合成を達成した。

Enzyme-catalyzed enantiomeric resolution of 3,8-dioxatricyclo[3.2.1.02,4]octane-6-carboxylic esters and the application to the synthesis of 3-epishikimic acid

M. Hamada, Y. Inami, Y. Nagai, T. Higashi, M. Shoji, S. Ogawa, K. Umezawa, T. Sugai

Tetrahedron: Asymmetry 20   2105-2111 2009.08

Research paper (scientific journal), Joint Work, Accepted

　View Summary

フランとアクリル酸のDiels-Alder反応、ヨードラクトン化を経て得られるラセミ体のエポキシエステルを、豚肝臓エステラーゼを用いて加水分解することにより速度論的光学分割した。

A Short-step Chemo-enzymatic Synthesis of a Precursor for L-Nucleosides from D-Lyxose

K. Kitsuda, J. Calveras, Y. Nagai, T. Higashi, T. Sugai

J. Mol. Catal. B: Enz. 59   197-200 2009.02

Research paper (scientific journal), Joint Work, Accepted

　View Summary

L-リキソースより出発し、リパーゼを用いた位置選択的エステル交換を活用して、L-ヌクレオシド合成に有用なL-リボフラノシドを合成した。

Chemoenzymatic Approach to Enantiomerically Pure (R)-3-Hydroxy-3-methyl-4-pentenoic Acid Ester and Its Application to Formal Total Synthesis of Taurospongin A

A. Fujino, T. Sugai

Adv. Synth. Catal. 358   1712-1716 2008.09

Research paper (scientific journal), Joint Work, Accepted

　View Summary

エポキシドヒドロラーゼ、ニトリルヒドラターゼ、アミダーゼを効果的に組み合わせ、(R)-3-ヒドロキシ-3-メチル-4-ペンテン酸エステルを調製、これにリパーゼで立体化学制御したジオールセグメントをGrubbs'クロスメタセシスして、タウロスポンジンＡの形式全合成を達成した。

Regio- and chemoselective manipulation under mild conditions on glucosamine derivatives for oligosaccharide synthesis and its application towards N-acetyl-D-lactosamine and Lewis X trisaccharide

Y. Nagai, N. Ito, I. Sultana, H. T. Sugai

Tetrahedron 64   9599-9606 2008.08

Research paper (scientific journal), Joint Work, Accepted

　View Summary

グルコサミン誘導体の位置選択的シリル化、オキサゾリジノン環形成により、４位を選択的に遊離とした物質とし、グリコシル化、３位を選択的に開環する新しい手法によりLacNAc誘導体を簡便に調製する方法を確立した。このものをフコシル化し、ルイスＸ３糖へと誘導した。

First total synthesis of modiolide A, based on the whole-cell yeast-catalyzed asymmetric reduction of a propargyl ketone

M. Matsuda, T. Yamazaki, K. Fuhshuku, T. Sugai

Tetrahedron 63   8752-8760 2007.07

Research paper (scientific journal), Joint Work, Accepted

　View Summary

スクリーニングによって得た立体障害の大きいカルボニル化合物を還元できる新しい還元酵素を有する微生物（酵母）を用い、プロパルギルケトン類を不斉還元、生成物から天然10員環ラクトン、モジオリドAの初の全合成を達成した。

Bacillus subtilis epoxide hydrolase-catalyzed preparation of enantiopure 2-methylpropane-1,2,3-triol monobenzyl ether and its application to expeditious synthesis of (R)-bicalutamide

A. Fujino, M. Asano, H. Yamaguchi, N. Shirasaka, A. Sakoda, M. Ikunaka, R. Obata, S. Nishiyama, T. Sugai

Tetrahedron Lett. 48   979-983 2007.03

Research paper (scientific journal), Joint Work, Accepted

　View Summary

B. subtilis由来の組み換えエポキシドヒドロラーゼを用いたラセミ体エポキシドの加水分解を鍵反応に、抗男性ホルモン剤であるビカルタミドの活性本体を効率よく合成する方法を開発した。

Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones

C. Hiraoka, M. Matsuda, Y. Suzuki, S. Fujieda, M. Tomita, K. Fuhshuku, R. Obata, S. Nishiyama, T. Sugai

Tetrahedron: Asymmetry 17   3357-3368 2006.12

Research paper (scientific journal), Joint Work, Accepted

　View Summary

立体障害の大きいカルボニル化合物を還元できる新しい還元酵素を有する微生物（酵母）をスクリーニング、基質特異性を明らかにした。

An Expeditious Chemo-enzymatic Synthesis of Dihydronorcapsaisin β-D-Glucopyranoside

I. Sultana, M. Shimamoto, R. Obata, S. Nishiyama, T. Sugai

Science and Technology of Advanced Materials 7   197-201 2006.03

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

フェノール類の効率的化学変換と、酵素（リパーゼ）を用いた位置・官能基選択的なアシル化により、辛味の非常に少ないカプサイシノイド誘導体を簡便に調製できる手法を確立した。

Synthesis and Biological Assessment of Hemiacetal Spiro Derivatives towards Development of Efficient Chemotherapeutic Agent

T. Ogamino, S Ohnishi, Y. Ishikawa, T. Sugai, R. Obata, S. Nishiyama

Science and Technology of Advanced Materials 7   175-183 2006.03

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

標題化合物を、電気化学的酸化、高原子価ヨウ素化合物を用いた酸化により調製、天然物合成に必要とされる基礎的知見を得た。

An Efficient Route to (S)-Azetidine-2-carboxylic Acid

Y. Futamura, M. Kurokawa, R. Obata, S. Nishiyama, T. Sugai

Biosci. Biotechnol. Biochem. 69   1892-1987 2005.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

標題化合物を、不斉補助基を導入したKrapcho脱アルコキシカルボニル化と、リパーゼを用いる速度論的光学分割を組み合わせることにより効率よく合成した。

Chemoenzymatic Route to Both Enantiomers of a 1-isopropyl-3a-methylocatahydroinden-4-one Derivative: a Synthetic Intermediate for Sesqui- and Diterpenoids

S. Fujieda, M. Tomita, K. Fuhshuku, S. Ohba, S. Nishiyama, T. Sugai

Adv. Synth. Catal. 347   1099-1109 2005.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

2,2-非対称置換-1,3-環状ジケトン類の酵母還元において、側鎖にtrapping armを導入することにより生成物を効果的に分離、還元の選択性理解に大きな役割を果たした。生成物からは光学活性テルペノイドへの変換を試みた。

Chemo-enzymatic Short-step Total Synthesis of Symbioramide

T. Takanami, H. Tokoro, D. Kato, S. Nishiyama, T. Sugai

Tetrahedron Lett. 46   3291-3295 2005.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

α,β－不飽和エステルをmCPBA酸化して生じるエポキシドを共通中間体とし、スフィンゴシンおよび光学活性α－ヒドロキシエステルを調製し、両者をリパーゼ存在下縮合させ、全12工程で海産セラミドの一種、シンビオラミドの全合成を達成した。

Short-Step and Scalable Synthesis of (±)-Cytoxazone

M. Asano, C. Nagasawa, M. Suzuki, S. Nishiyama, T. Sugai

Biosci. Biotechnol. Biochem. 69   145-148 2005.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

免疫調節物質として有用なサイトキサゾンのラセミ体を、p-メトキシ桂皮アルコールから５段階で効率よく全合成する方法を開発した。ペイン酸化剤を系内で発生させ、アジ化物イオンを直接反応させる新アジドヒドロキシル化を鍵段階とする。

Realization of the Synthesis of a,a-Disubstituted Carbamylacetates and Cyanoacetates Either by Chemical or Enzymatic Functional Group Transformation, Depending upon the Substrate Specificity of Rhodococcus amidase

M. Yokoyama, M. Kashiwagi, M. Iwasaki, K. Fuhshuku, H. Ohta, T. Sugai

Tetrahedron: Asymmetry 15   2817-2820 2004.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物の一種、Rhodococcus rhodochrousが生産するニトリルヒドラターゼ、アミダーゼのうち後者の立体選択的作用を活かし、対称ジニトリルから光学活性アミドカルボン酸を得た。生成物からL-N-メチルドーパへの誘導に成功した。

Plant-growth Inhibitory Activity of Heliannuol Derivatives

F. Doi, T. Ohara, T. Ogamino, T. Sugai, K. Higashinakasu, K. Yamada, H. Shigemori, K. Hasegawa, S. Nishiyama

Phytochemistry 65   1405-1411 2004.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ヘリアヌロール類の類縁体を合成し、各種植物の伸長阻害活性を観察することにより、新規農薬創製に貢献した。

Mechanistic Studies on Nitrosation-deaminocyclization of Mono-carbamylated Vicinal Amino Alcohols and Diols: A New Preparative in situ Formation of Ethanediazoic Acid for the Ethylation of Carboxylate under Mild Conditions

M. Suzuki, T. Sugai

Bull. Chem. Soc. Jpn. 77   1217-1227 2004.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

カルバミルアミノアルコールからニトロソ化を経由して、環状カルバマートへと変換する反応を時間分解IRで分析し、重要中間体を明らかにした。反応経路の考察から、ジアゾエタンの新規調製報、それを用いるエチルエステル化の新反応を開発した。

An Expeditious Route to N-Acetyl-D-galactosamine from N-Acetyl-D-glucosamine based on the Selective Protection of Hydroxyl Groups

N. Ito, Y. Tokuda, S. Ohba, T. Sugai

Bull. Chem. Soc. Jpn. 77   1181-1186 2004.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

N-アセチルグルコサミンの一段階選択的保護法を見出し、2級アルコールの立体反転を経て、天然に希少なN-アセチルガラクトサミンの短段階合成法を達成した。検討の過程で、新奇な骨格転位反応を見出した。

Concise Synthesis of 3-Deoxy-D-manno-oct-2-ulosonic Acid (KDO) as a Protected Form based on a New Transformation of a,b-Unsaturated Ester to a-Oxocarboxylic Acid Ester via Diol Cyclic Sulfite

A. Kuboki, T. Tajimi, Y. Tokuda, D. Kato, T. Sugai, S. Ohira

Tetrahedron Lett. 45   4545-4548 2004.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

α,β－不飽和エステルから、環状亜硫酸エステルを経由してα－ケトエステルを合成する新しい反応を見出し、マンノースを出発原料とするKDOの短段階合成法を確立した。

A Control of the Nitrile-hydrolyzing Enzyme Activity in Rhodococcus rhodochrous IFO 15564; Preferential Action of Nitrile Hydratase and Amidase Depending on the Reaction Condition Factors and its Application to the One-pot Preparation of Amides from Aldehydes

M. Kashiwagi, K. Fuhshuku, T. Sugai

J. Mol. Catal. B: Enz. 29   249-258 2004.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物の一種、Rhodococcus rhodochrousが有するニトリルヒドラターゼ、アミダーゼの活性を自在に制御する方法を見出し、アルデヒドからアミドへの同一容器内合成法を確立した。

Both Enantiomers of N-Boc-indoline-2-carboxylic Esters

M. Kurokawa, T. Sugai

Bull. Chem. Soc. Jpn. 77   1021-1025 2004.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

新しい化学合成の手法による、ラセミ体Boc-インドリンカルボン酸合成を達成、リパーゼの一種を用い速度論的光学分割を行った。

Scope and Limitation of Lithium-ethylenediamine/THF Mediated Cleavage at a-Position of Aromatics - Deprotection of Aryl Methyl Ethers and Benzyl Ethers under Mild Conditions

T. Shindo, Y. Fukuyama, T. Sugai

Synthesis 2004   692-700 2004.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リチウム－エチレンジアミン－THFという系が、芳香族化合物のα位での切断に非常に有用なことを見出し、それにもとづき2,6-ジメチルベンジル（MXM)基というアルコール保護基を開発した。

Unprecedented Chemo-enzymatic Synthesis of Stereochemically Pure 3-Acetoxy-2-methyl-2-vinylcycloalkanones

K. Fuhshuku, M. Tomita, T. Sugai

Tetrahedron Lett. 45   1763-1767 2004.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物の一種、Torulaspora delbrueckiiを用いた対称トリケトンの還元、引き続くラジカル開裂により新規光学活性素子を合成した。

Synthetic Studies on Bioactive Natural Products Employing Electrochemical Methodology, Synthesis of Heliannulol E.

F. Doi, T. Ogamino, T. Sugai, S. Nishiyama

Proc. Electrochem. Soc. (Mechanistic and Synthetic Aspects of Organic and Biological Electrochemistry) 2003   117-123 2003.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素による非対称化によって調製した原料から電気化学的酸化反応の手法によって標題の中間体を合成、これを環拡大反応に付して、ヘリアヌロールEの全合成ならびに類縁化合物の大量合成を達成した。

Enantiomerically pure Octahydronaphthalenones and Octahydroindenone: Elaboration of Substrate Overcame the Specificity of Yeast-mediated Reduction

K. Fuhshuku, M. Tomita, T. Sugai

Adv. Synth. Catal. 345   766-774 2003.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Torulaspora delbrueckiiを用いた各種ケトンの還元反応に対する基質特異性を明らかにした。プロキラル環状トリケトンの還元によって、光学活性アルコール類を調製、その反応に用いる酵素触媒を常温乾燥法によって試薬化した。

Enzyme-catalyzed Enantiomeric Resolution of N-Boc-proline as the Key-step in an Expeditious Route toward RAMP

M. Kurokawa, T. Shindo, M. Suzuki, N. Nakajima, K. Ishihara, T. Sugai

Tetrahedron: Asymmetry 14   1323-1333 2003.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体のBoc-プロリンメチルエステルに対し、リパーゼによる鏡像体選択的加水分解を行い、標題化合物へと誘導した。ミミズ由来プロテアーゼの反応性についても検討した。

Enantioselective Synthesis of Helianulol E; Structural Consideration of Natural Molecule

F. Doi, T. Ogamino, T. Sugai, S. Nishiyama

Tetrahedron Lett. 44   4877-4880 2003.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

プロキラル-3-置換グルタル酸ジエステルを、豚肝臓エステラーゼを用い非対称化し、生成物から天然有機化合物へと誘導した。

Synthesis of Bioactive Sesquiterpene Heliannuol E Involving a Ring-expansion Reaction of Spirodienones

F. Doi, T. Ogamino, T. Sugai, S. Nishiyama

Synlett    411-413 2003.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

電気化学的酸化反応の手法によって標題の中間体を調製、これを環拡大反応に付して、ヘリアヌロールEの全合成を達成した。

Magnetization Increase of Iron Oxide by Photoinduced Aggregation of Spiropyran

Y. Einaga, M. Taguchi, G. Li, T. Akitsu, G. Gu, T. Sugai, O. Sato

Chem. Mater. 15   8-10 2003.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

スピロピランの光誘起性集合体形成によって、酸化鉄の磁化が促進される現象を観察した。

Reversible Photo-controllable Magnetic Vesicles Consisting of Azobenzene

Y. Einaga, T.Yamamoto, T. Sugai, O. Sato

Chem. Mater. 14   4846-4850 2002.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

アゾベンゼンを構成成分とし、光照射によって可逆的に制御される磁気ベシクルに関する研究。

Access to Enantiomerically Pure Intermediates of Geosmin Synthesis Starting from (4aS,8S)-4,4a,5,6,7,8-Hexahydro-4a,8-dimethylnaphthalen-2(3H)-one

K. Fuhshuku, T. Sugai

Biosci. Biotechnol. Biochem. 66   2267-2272 2002.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Torulaspora delbrueckiiを用いて調製したWieland-Miescherケトンの光学活性体を出発原料として、標題化合物の合成を達成した。

Chemo-enzymatic Synthesis of Enantiomerically Pure (R)-2-Naphthylmethoxyacetic acid

M. Kimura, A. Kuboki, T. Sugai

Tetrahedron: Asymmetry 13   1059-1068 2002.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素法（速度論的光学分割、官能基変換）と化学法を組み合わせることにより、光学活性α－ナフチルメトキシ酢酸を合成した。

Expeditious Route to GlcNAc-Cbz-Asn by Chemo-enzymatic Synthesis

Takeshi Sugai, Yoshihide Tokuda, Yoichi Takahashi, Kaori Matoishi, Yukishige Ito

Synlett    57-69 2002.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

N-アセチルグルコサミンをグリコシルアミンに変換、一方Cbz-アスパラギン酸α－イソブチルエステル、β－フルオリドを調製しカップリング、加水分解酵素パパインを用い脱保護して目的物を短工程合成。

Microbial Asymmetric Reduction of α-Hydroxyketones in the anti-Prelog Selectivity

T. Tsujigami, T. Sugai, H. Ohta

Tetrahedron: Asymmetry 12   2543-2549 2001.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Yamadazyma farinosaを用いてα－ヒドロキシケトンを還元し、光学活性ジオールを調製した。

Lipase-catalyzed Asymmetrization of Diacetate of meso-2-(2-Propynyl)cyclohexane-1,2,3-triol toward the Total Synthesis of Aquayamycin

T. Matsumoto, T. Konegawa, H. Yamaguchi, T. Nakamura, T. Sugai, K. Suzuki

Synlett    1650-1652 2001.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

脂肪加水分解酵素リパーゼを用い、メソ体の2-(2-Propynyl)cyclohexane-1,2,3-triol に対応する酢酸エステルを加水分解、光学活性体を調製し、アクアヤマイシンの鍵合成中間体に変換した。

Preparation of Methyl Ursodeoxycholate in an interface Bioreactor: Use of a Mixed Solvent System to Increase the Solubilities of Substrate and Product

S. Oda, T. Sugai, H. Ohta

J. Biosci. Bioeng. 92   86-88 2001.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクターを用いて、微生物還元によるウルソデオキシコール酸エステルの合成に成功した。

Chemo-enzymatic Approach toward the Pure Enantiomers of 2-Methyl-1,3-Propanediol Mono p-Methoxybenzyl Ether

T. Akeboshi, Y. Ohtsuka, T. Ishihara, T. Sugai

Adv. Synth. Catal. 343   624-637 2001.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体の酵素加水分解を鍵段階として、標題化合物の光学活性体調製に成功した。プロキラル前駆体を、化学的手法による不斉アセタール開裂または酵素加水分解して部分光学活性体を合成、これを上述の方法と組み合わせ、酵素反応の生成物阻害を効果的に回避することができた。

Synthesis of Citronellyl Acetate in Growing Yeasts

S. Oda, T. Sugai, H. Ohta

Chem. Lett.    500-501 2001.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクター上、増殖期の酵母が生産するアセチル－CoAをドナーとする、シトロネロールのアセチル化に成功した。

Synthesis of Indanoxazolidinone based on the Lipase-catalyzed Resolution of the Corresponding N-Carbamylamino Derivative

M. Suzuki, C. Nagasawa, T. Sugai

Tetrahedron 57   4841-4848 2001.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼによる、N-カルバミルアミノアルコールをビスクロロアセチル体としたラセミ体基質の鏡像選択的加水分解により、光学活性体を調製した。溶解性の低い基質の反応促進に画期的な知見を得た。

Synthesis of Methyl Ursodeoxycholate via Microbial Reduction of Methyl 7-Ketolithocholate with Eubacterium aerofaciens JCM 7790 Grown on Two Kinds of Carbon and Hydride Sources, Glucose and Mannitol

S. Oda, T. Sugai, H. Ohta

J. Biosci. Bioeng. 91   179-183 2001.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクターを用い、微生物還元を鍵段階とするウルソデオキシコール酸エステルの調製に関し、エネルギー源となる糖類に関する検討を行った。

Synthesis of Methyl Ursodeoxycholate via Microbial Reduction of Methyl 7-Ketolithocholate in an Anaerobic Interface Bioreactor

S. Oda, T. Sugai, H. Ohta

J. Biosci. Bioeng. 91   202-207 2001.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

嫌気的条件下、界面バイオリアクターを用いた微生物還元を鍵段階として、ウルソデオキシコール酸エステルの調製を達成した。

Synthesis of Optically Active Citronellol, Citronellal, and Citronellic Acid by Microbial Oxidation and Double Coupling System in an Interface Bioreactor

S. Oda, T. Sugai, H. Ohta

Bull. Chem. Soc. Jpn. 73   2819-2823 2000.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクター上、微生物に含まれる複数の酵素機能を効率よく組み合わせるダブルカップリング法を開発し、標題化合物の調製に応用した。

Racemic and chiral crystals of cis-N',O-bis(chloroacetyl)-N-carbamyl-1-amino-2-indanol

M. Eishima, S. Ohba, M. Suzuki, C. Nagasawa, T. Sugai

Acta Cryst. sect. C C56   1391-1393 2000.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体と純粋な鏡像体の、標題化合物の結晶構造を明らかにし、物性（融点）の大きな違いを説明可能にする有益な知見を得た。

The First Synthesis of Both Enantiomers of α-[2H]-Phenylacetic Acid of High Enantiomeric Excess

K. Matoishi, S. Hanzawa, H. Kakidani, M. Suzuki, T. Sugai, H. Ohta

Chem. Commun.    1519-1520 2000.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物由来のアリールマロン酸脱炭酸酵素を用いて、標題化合物の合成に成功した。

Yamadazyma farinosa IFO 10896-Mediated Reduction of 4,4-Dimethoxy-2-Butanone as The Key-Step for the Preparatation of 1,3-Diols With Unsymmetrical Substituents

T. Yamazaki, A. Kuboki, H. Ohta, T. Mitzel, L. A. Paquette, T. Sugai

Synth. Commun. 30   3061-3072 2000.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Yamadazyma farinosaを用いた4,4-Dimethoxy-2-Butanoneの不斉還元と、誘導体に対するアリルインジウムの反応によって、標題化合物の新しい合成法開発に成功した。

MK800-62F1, a New Inhibitor of Apoptotic Cell Deth, from Streptomyces diastatochromogenes MI800-62F1. II. Structure Elucidation

Y. Yoshimoto, T. Sawa, H. Naganawa, T. Sugai, T. Takeuchi, M. Imoto

J. Antibiot. 53   575-578 2000.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物代謝産物である、標題化合物の相対、絶対立体配置を含めた構造を決定した。

N-Carbamylamino Alcohols as the Precursor of Oxazolidinones via Nitrosation-deamination Reaction

M. Suzuki, T. Yamazaki, H. Ohta, K. Shima, K. Ohi, S. Nishiyama

Synlett    189-192 2000.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

カルバミルアミノアルコールをニトロソ化によって活性化し、オキサゾリジノンへ閉環する新しい反応を見い出した。酵素反応と組み合わせ、有用な光学活性オキサゾリジノンを調製した。

Synthesis of Regioselectively Protected Forms of Cytidine Based on the Enzyme-catalyzed Deacetylation as the Key Step

A. Kuboki, T. Ishihara, E. Kobayashi, H. Ohta, T. Ishii, A. Inoue, S, Mitsuda, T. Miyazaki, Y. Kajihara

Biosci. Biotechnol. Biochem. 64   363-368 2000.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素を用いたヌクレオシドの位置選択的加水分解を鍵段階とする、ヌクレオチドの効率的合成に成功した。

The Access to Wieland-Miescher Ketone in an Enantiomerically Pure Form by a Kinetic Resolution with Yeast-mediated Reduction

K. Fuhshuku, N. Funa, T. Akeboshi, H. Ohta, H. Hosomi, S. Ohba, T. Sugai

J. Org. Chem. 66   129-135 2000.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Torulaspora delbrueckiiの還元を利用した速度論的光学分割で、光学活性Wieland-Miescher Ketoneおよび関連化合物を合成した。

Synthesis of (Rc,Ss)-1,1,1-Trifluoro-3-(p-tolylsulfinyl)-2-propanol by an Asymmetric Reduction with a Yeast, Yamadazyma farinosa, as a Key-step

A. Sakai, M. Bakke, H. Ohta, H. Kosugi, T. Sugai

Chem. Lett.    1255-1256 1999.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種、Yamadazyma farinosaによるanti-prolog不斉還元を利用し、標題化合物を効率よく合成した。

Action of L-Aminoacylase and L-Amino Acid Oxidase on 2-Amino-3-methyl-4-pentenoic acid [Δ(4)-Dehydroisoleucine and alloisoleucine] Stereoisomers: An Alternative Route to Stereochemically Pure Compound and the Application to the Synthesis of (R)-2-Methyl-1

M. Bakke, H. Ohta, U. Kazmaier, T. Sugai

Synthesis    1671-1677 1999.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

不斉クライゼン反応と酵素反応を組み合わせ、標題化合物の純粋な立体異性体を効率よく合成した。

Preparative-Scale Enzyme-catalyzed Synthesis of (R)-α-Fluorophenylacetatic Acid

Y. Fukuyama, K. Matoishi, M. Iwasaki, E. Takizawa, M. Miyazaki, H. Ohta, S. Hanzawa, H. Kakidani, T. Sugai

Biosci. Biotechnol. Biochem. 66   1164-1166 1999.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物脱炭酸反応を利用して、標題化合物を効率よく合成した。

Optical Resolution of Racemic Citronellol via a Double Coupling System in an Interface Bioreactor

S. Oda, T. Sugai, H. Ohta

J. Biosci. Bioeng. 87   473-480 1999.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクターを用いた二重カップリング法により、シトロネラールを光学分割した。

Lipase-catalyzed Enantiomeric Resolution of Ceramides

M. Bakke, M. Takizawa, T. Sugai, H. Ohta

J. Org. Chem. 63   6929-6938 1998.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体セラミド誘導体の酵素光学分割について検討し、固定化Candida antarcticaリパーゼが位置・立体選択性よく加水分解することを見出した。

Degradation of the Derivatives of N-Acetyl-D-glucosamine by Rhodococcus rhodochrous IFO 15564: Substrate Specificity and Its Application to the Synthesis of Allyl α-N-Acetyl-D-Glucosaminide

A. Kuboki, R. Komiya, T. Sekiguchi, K. Katsuragi, T. Sugai, H. Ohta

Biosci. Biotechnol. Biochem. 62   1581-1585 1998.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

Rhodococcus rhodochrousが生産するN-アセチルグルコサミンデアセチラーゼの基質特異性について検討し、アリル α-N-アセチルグルコサミニドの合成に応用した。

A Facile Access to Aryl α-Sialosides: the Combination of a Volatile Amine Base and Acetonitrile in Glycosidation of Sialosyl Chlorides

A. Kuboki, T. Sekiguchi, T. Sugai, H. Ohta

Synlett    479-482 1998.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

シアロシルハライドに対し、アセトニトリル中ジイソプロピルエチルアミンを塩基として用いるという条件下、アリールグリコシドの調製に成功した。

A Chemo-enzymatic Elaboration of a Quaternary Chiral Center; an Alternative Approach to the Side Chain of Furaquinocin D

T. Akeboshi, Y. Ohtsuka, H. Ohta, T. Sugai

Tetrahedron 54   7387-7394 1998.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼによる鏡像選択的加水分解を鍵段階として、不斉四級中心を有する光学活性合成原料の調製を行った。

Rhodococcus rhodochrous IFO 15564-mediated Hydrolysis of Alicyclic Nitriles and Amides: Its Stereoselectivity, and the Use for Kinetic Resolution and Asymmetrization

K. Matoishi, A. Sano, N. Imai, T. Yamazaki, M. Yokoyama, T. Sugai, H. Ohta

Tetrahedron: Asymmetry 9   1097-1102 1998.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

環状ニトリル、アミド類の微生物加水分解によって、光学活性アミドやカルボン酸類の合成に成功した。

Synthesis of Highly Oxygen-functionalized Derivatives of Dihydrodihydroxyphthalic Acid in Enantiomerically Enriched Forms

H. Ikeda, T. Sugai, H. Hosomi, S. Ohba, H. Ohta

Biosci. Biotechnol. Biochem. 62   396-400 1998.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ジヒドロジヒドロキシフタル酸より出発し、中間体の酵素を用いた不斉アシル化によって新しい光学活性物質を調製した。

Enzyme-mediated Optical Resolution of 2-Methyl-3,4-pentadien-1-ol, a Chiral Building Block Possessing Terminal Allenyl Group

T. Konegawa, Y. Ohtsuka, H. Ikeda, T. Sugai, H. Ohta

Synlett    1297-1299 1997.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いるアシル化、加水分解によって、標題化合物の光学分割に成功した。

A Chemo-enzymatic Synthesis of D-Allosamine Derivatives from Tri-O-acetyl-D-glucal

T. Sugai, H. Okazaki, A. Kuboki, H. Ohta

Bull. Chem. Soc., Jpn. 70   2535-2540 1997.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いる2,3-デヒドロ糖の位置選択的なアシル化を鍵段階として、D-アロサミンの合成を行なった。

Biocatalyst-mediated Efficient Preparation of Highly Enantiomerically Enriched (R)-5-Hexanolide

T. Sugai, K. Hamada, T. Akeboshi, H. Ikeda, H. Ohta

Synlett    797-798 1997.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母Pichia farinosaを用いるケトカルボン酸の還元によって、標題化合物を合成した。

Pivotal Role of (E)-3-Carbamoyl-1-propenylboronic Acid in the Combination of Suzuki-Miyaura Coupling and Enzyme Reactions: Synthesis of (3E,5E)- and (3E,5Z)-6-Phenyl-3,5-hexadienoic Acid

T. Sugai, M. Yokoyama, T. Yamazaki, H. Ohta

Chem. Lett.    797-798 1997.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

含ホウ素β,γ-不飽和ニトリルの微生物加水分解、パラジウムカップリングを組み合わせることによって、β,γ-不飽和カルボン酸類の新規な一般的合成法を開発した。

Brewers' Yeast-Mediated Synthesis of (1S,2S)-1-(2-Thienyl)-1,2-Propanediol and a Study on the Lipase-catalyzed Regioselective Introduction of Acyl Protective Group to the Diol Moiety

N. Mochizuki, T. Sugai, H. Ohta, T. Yokomatsu, S. Shibuya

Heterocycles 45   331-338 1997.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ビール酵母が生産するピルビン酸脱炭酸酵素を用い、1-チエニルプロパン-1,2-ジオールの効率的合成法の開発に成功した。

Biocatalytic Preparation of Sulfur-containing Optically Active Secondary Alcohols Based on the Reduction with an anti-Prelog Yeast, Pichia farinosa

Y. Ohtsuka, T. Sugai, H. Ohta

Bull. Chem. Soc. Jpn. 70   483-491 1997.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物Pichia farinosaおよびRhodococcus rhodochrousを組み合わせて、光学活性含硫アルコール類を効率よく合成した。

An Expeditious Route to N-Glycolylneuraminic Acid based on Enzyme-catalyzed Reaction

A. Kuboki, H. Okazaki, T. Sugai, H. Ohta

Tetrahedron 53   2387-2340 1997.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

シアル酸アルドラーゼの阻害作用について明らかにし、Rhodococcus rhodochrousを用いる純粋なマンノサミン調製法に立脚したN-グリコリルノイラミン酸の新規合成法の開発に成功した。

Lipase-catalyzed Efficient and Preparation of Long Chain Fatty Acid Ester Derivatives of Bile Acids: Biologicial Activity and Synthetic Application of the Products

M. Takizawa, M. Bakke, Y. Ohtsuka, T. Sugai, H. Ohta, H

Biosci. Biotechnol. Biochem 60   2059-2063 1996.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた胆汁酸メチルエステルの位置選択的アシル化を検討し、ウルソデオキシコール酸の新しい合成法の開発に成功した。

Action of Nitrile Hydratase of Rhocococcus rhodochrous IFO 15564 on the Derivatives of 2,5-Anhydro-D-allononitrile

M. Yokoyama, Y. Nakatsuka, T. Sugai, H. Ohta

Biosci. Biotechnol. Biochem 60   1540-1542 1996.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

2,5-アンヒドロ-D-アロニトリル誘導体の微生物加水分解反応を利用して、有用アミド類の合成に成功した。

Biocatalytic Approaches to Both Enantiomers of (2R*,3S*)-2-Allyloxy-3,4,5,6-tetrahydro-2H-pyran-3-ol

T. Sugai, H. Ikeda, H. Ohta

Tetrahedron 52   8123-8134 1996.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼによる鏡像選択的アシル化反応を利用して、標題化合物の両鏡像体を合成した。

Yeast-mediated Synthesis of Optically Active Diols with C2-Symmetry and (R)-4-Pentanolide

H. Ikeda, E. Sato, T. Sugai, H. Ohta

Tetrahedron 52   8113-8122 1996.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母Pichia farinosaを用いるジケトン、ケトカルボン酸の還元によって、標題化合物を合成した。

Preparation of Both Enantiomers of Methyl 3-Benzoyloxypentanoate by Enzyme-catalyzed Hydrolysis of Corresponding Racemic Nitrile and Amide

M. Yokoyama, N. Imai, T. Sugai, H. Ohta

J. Mol. Catal. Sect. B enzymatic 1   135-141 1996.05

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

3-ヒドロキシペンタンニトリル誘導体の微生物加水分解反応を利用して、光学活性なアミド、カルボン酸の合成に成功した。

Biocatalytic Preparation of R-(-)-4-(Phenylthio)-2-butanol and R-(-)-4-(Phenylsulfonyl)-2-butanol by the Sequential Use of Pichia farinosa and Rhodococcus rhodochrous

T. Sugai, Y. Ohtsuka, H. Ohta

Chem. Lett    233-234 1996.03

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

微生物Pichia farinosaおよびRhodococcus rhodochrousを組み合わせて、標題化合物を効率よく合成した。

Improved Conditions for the Production and Characterization of 1-Arylpropane-1,2-diols and Related Compounds

N. Mochizuki, S. Hiramatsu, T. Sugai, H. Ohta

Biosci. Biotechnol. Biochem 59   2282-2291 1995.12

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

酵母が生産するピルビン酸脱炭酸酵素を用い、1-アリールプロパン-1,2-ジオール類の効率的合成法の開発に成功した。

An Improved Enzymatic Procedure for Preparative-scale Synthesis of Sialic Acid and KDN

T. Sugai, A. Kuboki, S. Hiramatsu, H. Okazaki, H. Ohta

Bull. Chem. Soc. Jpn. 68   3581-3589 1995.12

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

ピルビン酸脱炭酸酵素を用いたピルビン酸の分解、N-アセチルグルコサミンの迅速異性化などを開発し、シアル酸やKDNの大量合成に成功した。

Chemo-enzymatic Synthesis of (R,R)-(-)-Pyrenophorin

T. Sugai, O. Katoh, H. Ohta

Tetrahedron 51   11987-11988 1995.10

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

微生物不斉還元、ニトリルの酵素加水分解、リパーゼを用いたラクトン化を組み合わせて、微生物代謝産物である(R,R)-(-)-Pyrenophorinの合成を行なった。

A New Strategy for the Cloning, Overexpression and One Step Purification of Three DHAP-Dependent Aldolases: Rhamnulose-1-phosphate Aldolase, Fuculose-1-phosphate Aldolase, and Tagatose-1,6-diphosphate Aldolase

E. Garcia-Junceda, G.-J. Shen, T. Sugai, C.-H. Wong

Bioorg. Med. Chem. 3   954-958 1995.09

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

数種のDHAP依存アルドラーゼを大腸菌で過剰発現し、糖質合成に応用した。

CMP-KDO Synthetase: Overproduction and Application to the Synthesis of CMP-KDO and Analogs

T. Sugai, C.-H. Lin, G. Shen, C.-H. Wong

Bioorg. Med. Chem. 3   313-320 1995.03

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

CMP-KDOシンテターゼを大腸菌で過剰発現し、フッ素を含む誘導体合成に応用し、これまでに提唱されていたCMP-KDOの立体化学を解明する大きな役割を果たした。

Application of Microbial Enantio-face Selective Hydrolysis in Natural Product Synthesis

O. Katoh, T. Sugai, H. Ohta

Tetrahedron: Asymmetry 5   1935-1944 1994.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

界面バイオリアクターを用いてエノールエステルを不斉加水分解し、生成物より出発して光学活性長鎖β-ヒドロキシエステル類の合成を行なった。

Biochemical Reduction of 3-Oxoalkanoic Esters by a Bottom Fermentation Yeast, Saccharomyces cerevisiae IFO 0565

N. Mochizuki, T. Sugai, H. Ohta

Biosci. Biotechnol. Biochem. 58   1666-1670 1994.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Saccharomyces cerevisiaeを用いた3-オキソアルカン酸エステルの還元による、(R)-3-ヒドロキシエステル類の合成を行なった。

A Synthesis of (R)-Recifeiolide by the Aid of Biochemical Reaction as the Key-step

N. Mochizuki, H. Yamada, T. Sugai, H. Ohta

Bioorg. Med. Chem. 1   71-75 1993.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵母の一種Pichia farinosaを用いた不斉還元を基盤として、微生物代謝産物である(R)-レシフェイオリドの合成を行なった。

Asymmetric Hydrolysis of a Disubstituted Malononitrile by the Aid of a Microorganism

M. Yokoyama, T. Sugai, H. Ohta

Tetrahedron: Asymmetry 4   1081-1084 1993.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

プロキラルな2,2-ジ置換マロノニトリル誘導体の微生物加水分解反応を利用して、光学活性なアミド、カルボン酸の合成に成功した。

Toward the Chemoenzymatic Synthesis of Lipid A

T. Sugai, H. Ritz&eacute;n, C.-H. Wong

Tetrahedron: Asymmetry 4   1051-1054 1993.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼによる鏡像体選択的アシル化反応を基盤として、リピドAの構成成分である(R)-3-ヒドロキシテトラデカン酸の合成を行なった。

Synthesis of 3-Deoxy-D-manno-2-octulosonic Acid (KDO) and its Analogs based on KDO Aldolase-catalyzed Reaction

T. Sugai, G.-J. Shen, Y. Ichikawa, C.-H. Wong

J. Am. Chem. Soc 115   413-421 1993.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

KDOアルドラーゼが触媒する反応を基盤として、新規なKDO誘導体の合成を行なった。

Unusual Stereoselectivity in Sialic Acid Aldolase Catalyzed Aldol Condensations: Synthesis of Both Enantiomers of High-Carbon Monosaccharides

C.-H. Lin, T. Sugai, R. L. Halcomb, Y. Ichikawa, C.-H. Wong

J. Am. Chem. Soc. 114   10138-10145 1992.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

シアル酸アルドラーゼが触媒する反応を基盤として、新規なシアル酸誘導体の合成を行なった。

Enantioselective Oxidation of Sulfinic Acid Esters with the Aid of a Microorganism

T. Kawasaki, N. Watanabe, T. Sugai, H. Ohta

Chem. Lett.    1611-1614 1992.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体スルフィン酸エステルの微生物酸化反応を利用して、光学活性なスルフィン酸エステルの合成に成功した。

Enzymatic Preparation of Glycerol-related Chiral Pool Possessing tert-Alkoxy Group

N. Watanabe, T. Sugai, H. Ohta

Chem. Lett.    657-660 1992.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

プロキラルな2-メチルグリセロール誘導体の酵素加水分解反応を利用して、光学活性な新規合成原料の開発に成功した。

A Synthesis of (4R,5R)-Isomer of 6-Phenyl-5-hydroxy-4-hexanolide, a Lateral Root Inducing Substance Isolated from Erwinia quercina

T. Sugai, H. Noguchi, H. Ohta

Biosci. Biotechnol. Biochem. 56   122-126 1992.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的ラクトン化反応を鍵段階とする、植物病原菌の代謝産物である標題化合物の合成を行なった。

Lipase-Mediated Preparation of Both Enantiomers of 2-Acetoxytetracosanoic Acid, an Intermediate for Sphingolipid Synthesis

T. Sugai, H. Ohta

Tetrahedorn Lett. 32   7063-7064 1991.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的アシル化反応を利用した、(R)-2-ヒドロキシテトラコサン酸の簡便合成法を開発した。

Microbial Hydrolysis of 3-Substituted Glutaronitriles

H. Kakeya, N. Sakai, A. Sano, M. Yokoyama, T. Sugai, H. Ohta

Chem. Lett.    1823-1824 1991.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

プロキラルな3-ヒドロキシグルタロニトリル誘導体の微生物加水分解反応を利用して、光学活性なアミド、カルボン酸の合成に成功した。

A Synthesis of (-)-Sitophilate by Yeast-mediated Reduction of an Enol Ester as the Key-step

T. Sugai, D. Sakuma, N. Kobayashi, H. Ohta

Tetrahedron 47   7237-7244 1991.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物を用いたエノールエステルの加水分解、立体選択的還元を鍵段階とし、標題化合物である昆虫フェロモンの合成研究を行なった。

A Synthetic Study of (-)-Dihydroedulan II and Related Compounds

T. Sugai, T. Yokochi, N. Watanabe, H. Ohta

Tetrahedron 47   7227-7236 1991.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的加水分解反応を鍵段階とし、標題化合物の合成研究を行なった。

Biochemical Preparation of Optically Active α-Hydroxy Acid Derivatives by Microbial Hydrolysis of Cyanohydrins and Its Application to the Synthesis of (R)-4-Dodecanolide

H. Kakeya, N. Sakai, T. Sugai, H. Ohta

Agric. Biol. Chem. 55   1877-1881 1991.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的加水分解反応、微生物を用いたシアノ基の加水分解反応を利用し、(R)-4-ドデカノリドの合成を行なった。

Biochemical Preparation of Optically Active 4-Hydroxy-β-ionone and Its Transformation to (S)-6-Hydroxy-α-ionone

H. Kakeya, T. Sugai, H. Ohta

Agric. Biol. Chem. 55   1873-1876 1991.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的加水分解反応を利用し、光学活性な6-ヒドロキシ-α-イオノンの合成を行なった。

A Synthesis of α-Tocopherol Intermediate

T. Sugai, N. Watanabe, H. Ohta

Tetrahedron: Asymmetry 2   371-376 1991.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

2-メチル-2-ベンジルオキシ-4-ペンテン酸の光学活性体を、対応するメチルエステルのリパーゼを用いた鏡像体選択的加水分解によって得、これを光学活性なトコフェロール合成中間体へと変換した。

Microbial Hydrolysis as a Potent Method for the Preparation of Optically Active Nitriles, Amides and Carboxylic Acids

H. Kakeya, N. Sakai, T. Sugai, H. Ohta

Tetrahedron Lett. 32   1343-1346 1991.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ニトリル化合物の微生物加水分解反応を利用して、光学活性なアミド、カルボン酸の合成に成功した。

A Simple Preparation of (R)-2-Hydroxy-4-phenylbutanoic Acid

T. Sugai, H. Ohta

Agric. Biol. Chem. 55   293-294 1991.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的アシル化反応を利用した、(R)-2-ヒドロキシ-4-フェニルブタン酸の簡便合成法を開発した。

Lipase-catalyzed Kinetic Resolution of 2-Hydroxyhexadecanoic Acid And Its Esters

T. Sugai, H. Ohta

Agric. Biol. Chem. 54   3337-3338 1990.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いた鏡像選択的アシル化反応を利用して、2-ヒドロキシヘキサデカン酸の光学分割を行なった。

A Synthesis of Japanese Beetle Pheromone Utilizing Lipase-catalyzed Enantioselective Lactonizaton

T. Sugai, S. Ohsawa, H. Yamada, H. Ohta

Synthesis    1112-1114 1990.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いたラクトン化を鍵反応として、マメコガネフェロモンの合成を行なった。

Enzymatic Preparation of Enantiomerically Enriched Tertiary α-Benzyloxy Acid Esters. Application to the Synthesis of (S)-(-)-Frontalin

T. Sugai, H. Kakeya, H. Ohta

J. Org. Chem. 55   4643-4647 1990.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

2-メチル-2-ベンジルオキシ-4-ペンテン酸の光学活性体を、対応するメチルエステルのリパーゼを用いた鏡像体選択的加水分解によって得、これを(S)-フロンタリンへと変換した。

Simple Synthesis of (R)-Hexadecanolide

H. Yamada, T. Sugai, H. Ohta, S. Yoshikawa

Agric. Biol. Chem. 54   1579-1580 1990.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ラセミ体ヒドロキシエステルを酵素を利用して鏡像体選択的にラクトン化させ、標題化合物を合成した。

Biochemical Preparation of (R)-Sulacatol

T. Sugai, H. Ohta

Agric. Biol. Chem. 54   1577-1578 1990.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

対応するケトンの微生物不斉還元により、標題化合物を合成した。

A Synthesis of (R)-(-)-Mevalonolactone by the Combination of Enzymatic and Chemical Methods

T. Sugai, H. Kakeya, H. Ohta

Tetrahedron 46   3463-3468 1990.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

2-メチル-2-ベンジルオキシ-4-ペンテン酸の光学活性体を、対応するメチルエステルのリパーゼを用いた鏡像体選択的加水分解によって得、これを(R)-メバロノラクトンへと変換した。

Alkylation of 2-Phenylsulfinylethanol

H. Ohta, S. Matsumoto, T. Sugai, Y. Okamoto

Tetrahedron Lett. 31   2895-2898 1990.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

光学活性なβ-アルコキシスルホキシドのアルキル化の立体化学について検討した。

Reduction of Acyl Enolates of α-Substituted β-Keto Esters by Bakers' Yeast

H. Ohta, N. Kobayashi, T. Sugai

Agric. Biol. Chem. 54   489-493 1990.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

パン酵母を用いたα-置換 β-ケトエステルの不斉還元、対応するエノールエステルの還元について検討した。

Structure of (±)-2-Hydroxymethyl-2,6-dimethylcyclohexan-1-ol

M. Morooka, S. Ohba, T. Sugai, H. Kakeya, H.; Ohta, Y. Saito

Acta Cryst. C46   168-170 1990.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

(-)-デオキシポドカルピン酸の重要合成中間体としての標題化合物の相対立体配置をX線結晶構造解析によって決定した。

A Synthesis of (-)-Deoxypodocarpic Acid Methyl Ester via an Enzymatic Enantioselective Hydrolysis of the Key Intermediate Enol Ester

T. Sugai, H. Kakeya, H. Ohta, M. Morooka, S. Ohba

Tetrahedron 45   6135-6144 1989.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを用いる環状エノールアセタートの鏡像選択的加水分解反応を鍵段階として、ジテルペンの一種である(-)-デオキシポドカルピン酸を合成した。

Lipase-catalyzed Highly Enantioselective Macrolactonization of Hydroxy Acid Esters in an Organic Solvent

H. Yamada, S. Ohsawa, T. Sugai, H. Ohta, S. Yoshikawa

Chem. Lett.    1775-1776 1989.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

リパーゼを触媒とし、長鎖ω-ヒドロキシカルボン酸メチルエステルから大環状ラクトンの合成を行なった。

Enzymatic Kinetic Resolution of Cyanohydrin Acetates and its Application to the Synthesis of (S)-(-)-Frontalin

H. Ohta, Y. Kimura, Y. Sugano, T. Sugai

Tetrahedron 45   5469-5476 1989.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

3級シアノヒドリンアセタートの鏡像選択的な微生物加水分解を鍵段階として、昆虫フェロモンである標題化合物を合成した。

Enzymatic Preparation of Ethyl (S)-3-Hydroxybutanoate with a High Enantiomeric Excess

T. Sugai, H. Ohta

Agric. Biol. Chem. 53   2009-2010 1989.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

パン酵母を用いたケトエステルの不斉還元により光学活性な出発原料を得、ひきつづきリパーゼを用いるアシル化によって不要な異性体を除去し、有用な光学活性原料である標題化合物を合成した。

Microbial Asymmetric Oxidation of 2-Alkoxyethylsulfides and a Facile Synthesis of Chiral Vinyl Sulfoxide

H. Ohta, S. Matsumoto, T. Sugai, Y. Okamoto

Chem. Lett.    625-628 1989.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

アルコキシエチルフェニルスルフィドの微生物酸化を鍵段階として、標的化合物を光学活性体として調製した。

Synthesis of (4S,5R)-5-Hydroxy-4-methyl-3-heptanone (Sitophilure), the Aggregation Pheromone of Sitophilus oryzae and S. zeamais

K. Mori, T. Yoshimura, T. Sugai

Liebigs Ann. Chem.    899-902 1988.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ジアステレオマー誘導体のクロマトグラフィーによる光学分割を利用して、昆虫フェロモンの一種であるsitophilureの合成を行なった。

Efficient Enzymatic Preparation of (1R,4S)-4-Hydroxy-2-cyclopentenyl Acetate

T. Sugai, K. Mori

Synthesis    19-22 1988.01

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素による不斉加水分解を利用して、光学活性プロスタグランジン類の重要合成中間体である標題化合物の調製を行なった。

Synthesis of (4aR,10aS)-(-)-8-Methoxy-1,1,4a-trimethyl-2-oxo-1,2,3,4,4a,9,10,10a-octahydrophenanthrene, an Optically Active Intermediate for the Synthesis of Diterpenes

T. Sugai, H. Tojo, K. Mori

Agric. Biol. Chem. 50   3127-3132 1986.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

パン酵母を用いたジケトンの不斉還元により光学活性な出発原料を得、ジテルペン合成の有用な中間体へと変換した。

Synthesis of the Racemic and Optically Active Forms of Gizzerosine, the Inducer of Gizzard Erosion in Chicks

K. Mori, T. Sugai, Y. Maeda, T. Okazaki, T. Noguchi, H. Naito

Tetrahedron 41   5307-5311 1985.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ニワトリ筋胃潰瘍原因物質であるジゼロシンの両鏡像体を合成し、(S)-体が活性の本体であることを明らかにした。

Synthesis of (S)-2-Hydroxy-β-ionone, Employing (S)-3-Hydroxy-2,2-dimethylcyclohexanone as the Chiral Starting Material

M. Yanai, T. Sugai, K. Mori

Agric. Biol. Chem. 49   2373-2377 1985.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

パン酵母を用いたジケトンの不斉還元により光学活性出発原料を得、タバコ香気改良物質である標題化合物を合成した。

Biochemical Preparations of Both the Enantiomers of Methyl 3-Hydroxypentanoate and their Conversion to the Enantiomers of 4-Hexanolide, the Pheromone of Trogoderma glabrum

K. Mori, H. Mori, T. Sugai

Tetrahedron 41   919-925 1985.03

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物的手法を用いて3-ヒドロキシペンタン酸メチルを合成し、カツオブシムシのフェロモンである4-ヘキサノリドを合成した。

Preparation of (R)-Ibuprofen and Related Carboxylic Acids Using Microbial Oxidation of an Aromatic Hydrocarbon by Rhodococcus sp. BPM 1613

T. Sugai, K. Mori

Agric. Biol. Chem. 48   2501-2504 1984.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

芳香族炭化水素を微生物酸化し、消炎剤である(R)-イブプロフェンを得た。

Synthesis of Both the Enantiomers of 4-Dodecanolide, a Defensive Secretion of Rove Beetles

T. Sugai, K. Mori

Agric. Biol. Chem. 48   2496-2500 1984.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

アミノ酸の両鏡像体より出発し、甲虫の一種ハネカクシの防御物質である4-ドデカノリドを短工程で合成した。

Both Enantiomers of 8-Hydroxyhexadecanoic Acid Inhibit the Spore Germination of Lygodium japonicum

T. Sugai, K. Mori

Agric. Biol. Chem. 48   2155-2156 1984.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

アミノ酸の酵素を用いた不斉加水分解により得られる両鏡像体より出発し、カニクサの内生的胞子発芽阻害因子を合成した。両鏡像体に阻害活性があった。

The Absolute Structure and Activity Relationships of Major Secondary Alcohols of Pyrethroid Insecticides

N. Matsuo, T. Yano, H. Yoshioka, S. Kuwahara, T. Sugai, K. Mori

IUPAC Pesticide Chemistry, 'Human Welfare and the Environment'    279-284 1983.12

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

合成ピレスロイドの2級アルコール部分の立体化学と殺虫活性の関係について検討した。

微生物を利用した3-ヒドロキシブタン酸エチルの両鏡像体の調製法

須貝 威、藤田 満、森 謙治

日本化学会誌    1315-1320 1983.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

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微生物による不斉還元や、それらの生産するポリマーを用いて、3-ヒドロキシブタン酸エチルの両構造体の大量調製法を確立した。

Preparation of Optically Active Secondary Alcohols Related to Synthetic Pyrethroids by Microbial Asymmetric Hydrolysis of the Corresponding Acetates

T. Sugai, S. Kuwahara, C. Hoshino, N. Matsuo, K. Mori

Agric. Biol. Chem. 46   2579-2585 1982.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

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微生物による対応する酢酸エステルの鏡像体選択的加水分解を利用して、合成ピレスロイドのアルコール部分の光学活性体を調製した。

Ethyl (S)-3-hydroxybutanoate as a Starting Material for the Synthesis of (S)-(-)-Citronellol and Other Chiral Alcohols

T. Sugai, K. Mori

Synthesis    752-753 1982.07

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

パン酵母を用いた不斉還元で得られる3-ヒドロキシブタン酸エチルの(S)体より出発し、香料物質(S)-シトロネロール等の光学活性アルコールを合成した。

Inhibition of cellular and animal inflammatory disease models by nf-κb inhibitor dhmeq

Ma J., Zhang Y., Sugai T., Kubota T., Keino H., El-Salhy M., Ozaki M., Umezawa K.

Cells (Cells)  10 ( 9 )  2021.09

　View Summary

General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.

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Syntheses of Englerin A, a Potent Renal Cancer Inhibitor

Hagihara S., Hanaya K., Sugai T., Shoji M.

Asian Journal of Organic Chemistry (Asian Journal of Organic Chemistry)  8 ( 1 ) 48 - 62 2019.01

ISSN  21935807

　View Summary

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Mankind has been searching for anticancer drugs from nature and artificial compounds. Since the discovery of englerin A, a guaiane sesquiterpene possessing the characteristic tricyclic 5–6-5 fused ring framework with contiguous seven stereogenic centers and isolated from Phyllanthus engleri, many synthetic groups have enthusiastically launched and accomplished its the chemical synthesis. All the synthetic groups focused on how to efficiently construct the tricyclic framework containing oxygen bridge with various approaches. In this review, the total and formal syntheses of englerin A reported to date are summarized.

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Recent examples of the use of biocatalysts with high accessibility and availability in natural product synthesis (Tetrahedron Report No. 1164)

Sugai T., Higashibayashi S., Hanaya K.

Tetrahedron (Tetrahedron)  74 ( 27 ) 3469 - 3487 2018.07

ISSN  00404020

　View Summary

© 2018 Elsevier Ltd Utilization of biocatalysts with high accessibility and availability, which have recently been applied in the preparation of enantiomerically enriched starting materials and synthetic intermediates for natural product syntheses (mainly 2013–2017) are summarized in this review. The main contents are as follows: 1) recruitment of biocatalysts for the transformation of organic compounds; 2) special precautions for preparative-scale biocatalytic synthetic experiments; 3) asymmetric reduction of carbonyl substrates; 4) kinetic resolution of alcohol and carboxylate enantiomers; 5) desymmetrization of multifunctional alcohol and carboxylate substrates; and 6) recognition of remote and non-central chirality.

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Process Development with Bifunctional Chiral Epoxides to Acess Single Enantiomers of Pharmaceutical Intermediates

M. Ikunaka, T. Sugai

J. Oil Palm Res.    143-158 2008.10

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

第二級および第三級エポキシドの化学－酵素複合的手法による調製と生成物の医薬品合成への応用について解説した。

Enzyme Reactions as Key-steps for the Synthesis of Terpenoids, Degraded Carotenoids, Steroids, and Related Substances

K. Fuhshuku, S. Oda, T. Sugai

Recent Res. Devel. Org. Chem. 6   57-74 2002.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

光学活性テルペノイド、分解カロテノイド、ステロイド類の合成における酵素・微生物の利用について解説した。

Application of Enzyme- and Microorganism-catalyzed Reactions to Organic Synthesis

T. Sugai

Curr. Org. Chem. 3   373-406 1999.06

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

有機合成における酵素・微生物触媒反応の利用について、著者の研究を中心に解説した。

Biocatalysis in Organic Synthesis: The Use of Nitrile- and Amide-Hydrolyzing Microorganisms

T. Sugai, T. Yamazaki, M. Yokoyama, H. Ohta

Biosci. Biotechnol. Biochem. 61   1419-1427 1997.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

ニトリル・アミド類の微生物・酵素加水分解について概説した。

Aldolase Catalyzed Reaction for Carbohydrate Synthesis

T. Kajimoto, T. Sugai, C.-H. Wong

Trends in Glycosci. Glycotechnol. 5   193-207 1993.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

アルドラーゼが触媒する反応を基盤とする、新規な糖質誘導体の合成に関する成果について概説した。

8-Quinolinol誘導体の化学反応とバイオケミカルツール・酵素阻害剤への応用

青木 伸、有安真也、花屋賢悟、久松洋介、須貝 威

有機合成化学協会誌 74   482-493 2016.04

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物酵素触媒の高度活用に関し、合成経路デザインにおける、基質分子工学と触媒探索の重要性―について解説した。

酵素を用いて鏡像異性体を分ける、創る、速度論的分割の力

古田未有、桑田和明、花屋賢悟、庄司 満、須貝 威

生物工学会誌 92   298-302 2014.06

Research paper (conference, symposium, etc.), Joint Work, Accepted

日本農芸化学会が人材育成に果たすべきこと―関東支部の活動を例として（巻頭言）

須貝 威

化学と生物 52   417-418 2014.02

Research paper (conference, symposium, etc.), Single Work, Accepted

微生物酵素触媒を高度に活用する―合成経路デザインにおける、基質分子工学と触媒探索の重要性―

古田未有、花屋賢悟、庄司満、須貝 威

有機合成化学協会誌 71   237-246 2013.03

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物酵素触媒の高度活用に関し、合成経路デザインにおける、基質分子工学と触媒探索の重要性―について解説した。

新しいNF-κB阻害剤DHMEQの生物有機化学と抗がん・抗炎症剤への展望

梅澤一夫、須貝 威

化学と生物 49   406-414 2011.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

新しいNF-κB阻害剤DHMEQの生物有機化学とその応用展開について解説した。

微生物酵素反応を活用するスタチン中間体の合成研究

清水賢一、坂本真希、濱田 学、東 利則、庄司 満、須貝 威

月刊 化学工業 61   425-430 2010.06

Research paper (conference, symposium, etc.), Joint Work

　View Summary

リパーゼを用いた速度論的光学分割を鍵段階とするスタチンの合成研究を、著者らの実例を中心に紹介した。不要な鏡像異性体を微生物還元でリサイクルする検討も述べている。

プロセス化学の新潮流－酵素触媒と化学合成をいかに相乗的に活用するか

東 利則、須貝 威、濱田 学、梅澤一夫

バイオインダストリー 26   14-20 2009.01

Research paper (conference, symposium, etc.), Joint Work

　View Summary

有機合成における微生物・酵素触媒反応の先進的実例を、特に著者らの光学活性物質合成の研究を中心に概説した。

酵素光学分割を基盤とする、光学活性アミノ酸・アミノアルコール調製に向けたプロセス開発

須貝 威、冨宿 賢一、小畠 りか、西山 繁

ケミカルエンジニヤリング 59   691-696 2006.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

有機合成における微生物・酵素触媒反応の先進的実例を、特に著者らのアミノ酸合成の研究を中心に概説した。

酵素・微生物触媒反応を基盤とする有用物質合成への展開

冨宿 賢一、西山 繁、須貝 威

有機合成化学協会誌 64   664-676 2006.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

有機合成における微生物・酵素触媒反応の先進的実例を、著者らの研究を中心に概説した。

物質合成の設計図にブレークスルーを：酵素触媒の活躍と未来

須貝 威

バイオインダストリー 23   5-6 2006.03

Research paper (conference, symposium, etc.), Single Work

　View Summary

先端的、かつ環境に優しい物質変換の新手法としての酵素触媒合成について概要を紹介した。

生命分子の変化をつかさどるタンパク質触媒－酵素　触媒のしくみ、鏡像異性とのかかわりから物質合成まで

須貝 威、浅野正義

化学と教育 53   436-439 2005.08

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素触媒のしくみ、鏡像異性体の認識、物質変換、触媒効率向上の方法など、著者らの研究例も含め平易に解説した。

モノづくりの基盤としての有機合成反応&#8722;酵素触媒を例として

須貝 威、鈴木麻珠三、冨宿賢一

化学と生物 42   133-139 2004.02

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

微生物酵素を用い、光学活性物質を調製する方法論に関する最近の進歩、天然有機化合物合成への応用について解説した。

酵素反応は、信頼性の高い光学分割法：そのしくみと新しい展開

須貝 威

ファルマシア 38   1168-1172 2002.12

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

加水分解酵素を用い、光学活性物質を調製する原理と最近の進歩について解説した。

みんなで作る最新実験プロトコール：加水分解酵素を用いる鏡像体の分離－選択性の評価、実施上の注意

黒川真行、須貝 威

日本農芸化学会誌 76   1094-1097 2002.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

加水分解酵素を用いた鏡像体分離の原理、実施上の注意などについて著者らの研究を中心に解説した。

微生物・酵素反応を基盤とする複合糖質関連物質の合成研究

須貝 威、窪木 厚人、場家 幹雄、関口 卓宏、太田 博道

有機合成化学協会誌 56   489-499 1998.05

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

酵素加水分解、アシル化、アルドール反応などを利用した複合糖質関連物質の合成について、著者らの研究を中心に概説した。

シアル酸アルドラーゼを用いた糖質合成に関する最近の話題

須貝 威

生物工学会誌 74   136 1996.03

Research paper (conference, symposium, etc.), Single Work

　View Summary

シアル酸アルドラーゼを用いた糖質合成について著者の研究を中心に概説した。

不斉合成で活躍するCandida rugosa リパーゼ

須貝 威、太田 博道

化学 51   132 1996.01

Research paper (conference, symposium, etc.), Single Work

　View Summary

リパーゼを利用する不斉合成について概説した。

有機合成化学における生体触媒：古くて新しいピルビン酸脱炭酸酵素

須貝 威

化学と工業 48   143-146 1995.02

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

ピルビン酸脱炭酸酵素を用いた光学活性物質、糖質合成について著者の研究を中心に概説した。

生体触媒を用いる不斉合成及び有用物質生産への応用（日本農芸化学会奨励賞受賞総説）

須貝 威

日本農芸化学会誌 69   9-16 1995.01

Research paper (conference, symposium, etc.), Single Work

　View Summary

微生物・酵素などの生物触媒を利用した光学活性物質、糖質合成について著者の研究を中心に概説した（日本農芸化学会奨励賞受賞記念）。

生体触媒を用いる光学活性ヒドロキシ酸の合成

須貝 威、土屋 滋夫、望月 直樹、太田 博道

有機合成化学協会誌 53   32-42 1995.01

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

酵素加水分解、アシル化、微生物還元などを利用した光学活性ヒドロキシ酸類の合成について、著者らの研究を中心に概説した。

生体触媒を用いる有機合成－糖鎖合成への応用

須貝 威

Glyco News 2   3-13 1994.06

Research paper (conference, symposium, etc.), Single Work

　View Summary

酵素が触媒する反応を基盤とする、新規な糖質誘導体の合成に関する成果について概説した。

複雑な糖鎖合成のためのバイオリアクターシステム

須貝 威、太田 博道

バイオサイエンスとインダストリー 50   40-43 1992.07

Research paper (conference, symposium, etc.), Joint Work

　View Summary

糖転移酵素を用いた糖鎖合成技術の最近の進歩について概説した。

リパーゼ －加水分解で光学活性体をつくる－

須貝 威、太田 博道

有機合成化学協会誌 48   1070-1071 1990.11

Research paper (conference, symposium, etc.), Joint Work, Accepted

　View Summary

加水分解酵素であるリパーゼの有機合成への応用に関して、著者らの研究を中心に概説した。

有機溶媒中の酵素反応を利用した光学分割

須貝 威

化学と工業 39   544-545 1986.06

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

有機溶媒中の酵素反応、特にリパーゼやプロテアーゼを利用した光学分割について解説した。

有機合成に微生物をどう使うか（実験アラカルト）

須貝 威、森 謙治

化学 40   678-679 1985.07

Research paper (conference, symposium, etc.), Joint Work

　View Summary

有機合成に微生物をどう利用するか、という課題について実験技術を中心に初心者向けに解説した。

天然物合成における微生物や酵素の利用

森 謙治、須貝 威

有機合成化学協会誌 41   1044-1053 1983.10

Research paper (conference, symposium, etc.), Joint Work

　View Summary

天然物合成における微生物や酵素の利用について、著者らの研究を中心に概説した。

対称ジエステルの微生物不斉加水分解

須貝 威

化学と工業 36   744-745 1983.06

Research paper (conference, symposium, etc.), Single Work, Accepted

　View Summary

対称ジエステルを微生物酵素で不斉加水分解し、有用天然生物活性物質に導くアプローチについて解説した。

Synthesis and property of 2,2-difluoro-1,4-diazaborole

Nakahara M., Wada Y., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

Chemistry Letters 53 ( 5 )  2024.05

ISSN  03667022

　View Summary

The synthesis of 2,2-difluoro-1,4-diazaboroles was achieved through the condensation of aliphatic acyltrifluoroborates and amino-N-heteroarenes under acidic conditions. Various N-heteroarenes, including pyridine, pyrimidine, pyridazine, thiazole, and isoquinoline, were successfully employed in the reaction. Among the synthesized 2,2-difluoro-1,4-diazaboroles, the one with an isoquinoline structure exhibited the most intense light blue emission.

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Utilization of Lipase-Catalyzed Acetylation and Deacetylation in the Synthesis of a Natural Product with a Hydroquinone Skeleton

Sugai T., Honda K., Hashimoto R., Hanaya K., Higashibayashi S.

Asian Journal of Organic Chemistry  2024

　View Summary

Elaborated conditions for lipase-catalyzed preferential monoacetylation enabled the large-scale preparation of hydroquinone monoacetate. This product was then applied to the synthesis of tournefolin B, a highly oxygenated prenylated hydroquinone of plant origin (Tournefortia sarmentosa Lam.). During the course of the synthetic transformations, lipase-catalyzed deacetylation under mild conditions was demonstrated.

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Transition-Metal-Free β-Selective C-Glycosylation of β-Glycosyl Boronates via Stereoretentive 1,2-Migration

Yasutomi H., Takeda D., Yoritate M., Higashibayashi S., Sugai T., Hirai G.

Synlett 34 ( 4 ) 347 - 352 2023.03

ISSN  09365214

　View Summary

C-Glycoside analogues of native glycans are useful molecular tools for medicinal chemistry and chemical biology due to their resistance to cellular glycoside hydrolases. We previously reported an α-selective direct C-glycosylation of 2-deoxy-β-glycosyl boronate through a Ni/photoredox-catalyzed stereoinvertive cross-coupling reaction. Here we report a complementary stereoretentive synthetic method for the preparation of β-C-glycosides from a similar boronate precursor through the addition of a C(sp2) anion followed by 1,2-migration of the glycosyl donor.

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Copper-Catalyzed Stereoselective Borylation and Palladium-Catalyzed Stereospecific Cross-Coupling to Give Aryl C-Glycosides

Kurahayashi K., Hanaya K., Sugai T., Hirai G., Higashibayashi S.

Chemistry - A European Journal (Chemistry - A European Journal)  29 ( 6 )  2023.01

ISSN  09476539

　View Summary

Metabolically stable C-glycosides are an essential family of compounds in bioactive natural products, therapeutic agents, and biological probes. For their application, development of synthetic methods by connecting glycosides and aglycons with strict stereocontrol at the anomeric carbon, as well as with high functional-group compatibility and environmental compatibility is a pivotal issue. Although Suzuki–Miyaura-type C(sp3)−C(sp2) cross-coupling using glycosyl boronates is a potential candidate for the construction of C-glycosides, neither the cross-coupling itself nor the facile synthesis of the coupling precursor, glycosyl boronates, have been achieved to date. Herein, it was succeeded to develop a copper-catalyzed stereoselective one-step borylation of glycosyl bromides to glycosyl boronates and palladium-catalyzed stereospecific cross-coupling of β-glycosyl borates with aryl bromides to give aryl β-C-glycosides, in which the β-configuration of the anomeric carbon of the glycosyl trifluoroborates is stereoretentively transferred to that of the resulting aryl C-glycosides.

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Sluggish Forwarding from Excitement and Regret in Enzyme Catalysis and Organic Synthesis

Sugai T.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 81 ( 9 ) 896 - 899 2023

ISSN  00379980

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Single-Step N-Terminal Modification of Proteins via a Bio-Inspired Copper(II)-Mediated Aldol Reaction

Hanaya K., Yamoto K., Taguchi K., Matsumoto K., Higashibayashi S., Sugai T.

Chemistry - A European Journal (Chemistry - A European Journal)  28 ( 47 )  2022.08

ISSN  09476539

　View Summary

The chemical modification of proteins is an effective technique for manipulating the properties and functions of proteins, and for creating protein-based materials. The N-terminus is a promising target for single-site modification that provides modified proteins with uniform structures and properties. In this paper, a copper(II)-mediated aldol reaction with 2-pyridinecarboxaldehyde (2-PC) derivatives is proposed as an operationally simple method to selectively modify the N-terminus of peptides and proteins at room temperature and physiological pH. The copper(II) ion activates the N-terminal amino acids by complexation with an imine of the N-terminal amino acid and 2-PCs, realizing the selective formation of the nucleophilic intermediate at the N-terminus. This results in a stable carbon-carbon bond between the 2-PCs and the α-carbon of various N-terminal amino acids. The reaction is applied to four different proteins, including biopharmaceuticals such as filgrastim and trastuzumab. The modified trastuzumab retains the human epidermal growth factor receptor 2 recognition activity.

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One-Step Synthesis of Acylborons from Acyl Chlorides through Copper-Catalyzed Borylation with Polystyrene-Supported PPh<inf>3</inf>Ligand

Nakahara M., Kurahayashi K., Hanaya K., Sugai T., Higashibayashi S.

Organic Letters (Organic Letters)  24 ( 30 ) 5596 - 5601 2022.08

ISSN  15237060

　View Summary

We developed a one-step synthesis of acylborons from both readily available acyl chlorides and bis(pinacolato)diboron through copper(I)-catalyzed borylation. Under the reaction conditions using tBuOLi, polystyrene-supported triphenylphosphine as a copper ligand was found to promote the borylation of acyl chlorides while suppressing alcoholysis. This method enables the facile synthesis of potassium acyltrifluoroborates.

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Synthesis of 1H-2-Benzopyran-5,8-dione Skeleton through a Cascade Reaction between Benzoquinone and β-Ketoester

Nakahara M., Ohtsu H., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

Chemistry Letters (Chemistry Letters)  51 ( 4 ) 356 - 359 2022.04

ISSN  03667022

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The 1H-2-benzopyran-5,8-dione structure was synthesized by a cascade reaction through Michael addition, elimination of HBr, and O-alkylation between a dibromobenzoquinone derivative and β-ketoesters under basic conditions. The reaction using potassium carbonate and 18-crown-6 in THF was the best condition, giving 1H-2-benzopyran-5,8-dione derivatives in good yields. The UV-vis absorption spectrum and cyclic voltammogram of the synthesized 1H-2-benzopyran-5,8-dione derivative were measured, clarifying the photophysical and redox properties.

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1,2-Rearrangement from o-Quinols to Multisubstituted Catechols via Retro Diels-Alder Reaction of o-Quinol Dimers

Hashimoto R., Hanaya K., Sugai T., Higashibayashi S.

Bulletin of the Chemical Society of Japan (Bulletin of the Chemical Society of Japan)  95 ( 4 ) 663 - 672 2022

ISSN  00092673

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The 1,2-rearrangement of o-quinols has been a long-standing unsolved problem since 1958. Although the rearrangement is expected to be useful for syntheses of catechol derivatives, it is hampered by many competing reactions and has not been developed as a useful methodology. Here, we succeeded in settling this problem by a first systematic thorough investigation, establishing the 1,2-rearrangement as a cascade reaction with a retro Diels-Alder reaction from o-quinol dimers. This is a useful strategy for syntheses of substituted catechols used as synthetic building blocks for bioactive compounds and material molecules. o-Quinol dimers were synthesized by improved oxidative hydroxylation of substituted phenols followed by spontaneous Diels-Alder reaction. The dimers then underwent the retro Diels-Alder reaction to regenerate the o-quinols followed by 1,2-rearrangement under neutral heating conditions at an appropriate temperature depending on the migratory substituent, furnishing substituted catechols in good yields. The competing reactions such as an elimination of a substituent or α-ketol rearrangement were minimized by controlling the reaction temperature.

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Chemoselectivity-independent Cu-mediated coupling to construct the hydroquinoline skeleton of symbioimine

Fujita R., Hanaya K., Sugai T., Higashibayashi S.

Scientific Reports (Scientific Reports)  11 ( 1 )  2021.12

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Construction of the hydroquinoline skeleton of symbioimine by Cu-mediated N-alkenylation or O-alkenylation of an allyl aminoalcohol, in which either chemoselectivity could lead to the target compound, was investigated. O-alkenylation followed by Claisen rearrangement was favored with high selectivity under a ligand-free condition. Subsequent intramolecular condensation furnished the hydroquinoline skeleton of symbioimine.

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Chemoenzymatic semisynthesis of caffeic acid β-phenethyl ester, an antioxidative component in propolis, from raw coffee bean extract

Hashimoto R., Iai H., Fujita R., Hanaya K., Higashibayashi S., Inoue H., Sugai T.

Bioscience, Biotechnology and Biochemistry (Bioscience, Biotechnology and Biochemistry)  85 ( 3 ) 476 - 480 2021.03

ISSN  09168451

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Caffeic acid ß-phenethyl ester (CAPE), an antioxidative bioactive catechol isolated from propolis, was semisynthesized from chlorogenic acid and related compounds in an extract of raw (unroasted) Robusta coffee (Coffea canephora) beans in 5 steps and a total yield of 31%. Oxidative degradation of the intermediates and target molecule was prevented by alkaline hydrolysis of the chlorogenic acids in the presence of sodium dithionite (Na2S2O4) and deprotection of the catecholic diacetate precursor by Candida antarctica lipase B-mediated transesterification as the final step.

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