Papers - Hanaya, Kengo

Chemoenzymatic approaches to the synthesis of the (1S,2R)-isomer of benzyl2-hydroxycyclohexanecarboxylate

TSUNEKAWA Ryuji, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SHOJI Mitsuru, SUGAI Takeshi

Mol. Catal. 444   84 - 89 2018

Research paper (scientific journal), Joint Work, Accepted

Synthesis of trilobatin from naringin via prunin as the key intermediate: acidic hydrolysis of the α-rhamnosidic linkage in naringin under improved conditions

KURAHAYASHI Kazuki, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SUGAI Takshi

Bioscience, Biotechnology, and Biochemistry (Bioscience, Biotechnology and Biochemistry)  82 ( 9 ) 1463 - 1467 2018

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

TSUNEKAWA Ryuji, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SUGAI Takeshi

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

Research paper (scientific journal), Joint Work, Accepted,  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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Synthesis of 3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and Reductive Nucleophilic Attack on a Branched Aliphatic Aldehyde

NAGAI Toshiya, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SHOJI, Mitsuru, SUGAI Takeshi

CHEMICAL and PHARMACEUTICAL BULLETIN (Chemical and Pharmaceutical Bulletin)  66 ( 3 ) 334 - 338 2018

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.

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

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

Chemistry Letters (Chemistry Letters)  47 ( 11 ) 1357 - 1359 2018

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 oroxylin A starting from naturally abundant baicalin

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

Heterocycles (Heterocycles)  97 ( 2 ) 1165 - 1174 2018

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

FUJITANI Ban, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SHOJI Mitsuru, SUGAI Takeshi

Tetrahedron 73 ( 51 ) 7217 - 7222 2017.12

Research paper (scientific journal), Joint Work, Accepted

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

TSUNEKAWA Ryuji, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SHOJI Mitsuru, SUGAI Takeshi

MolecularCatalysis (ELSEVIER)  444   84 - 89 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

KUWATA Kazuaki, HANAYA Kengo, HIGASHIBAYASHI Shuhei, SUGAI Takeshi, SHOJI Mitsuru

Tetrahedron 73 ( 41 ) 6039 - 6045 2017.10

Research paper (scientific journal), Joint Work, Accepted

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

HAGIHARA Shuichi,HANAYA Kengo, SUGAI Takeshi, SHOJI Mitsuru

The Journal of Antibiotics (Journal of Antibiotics)  71 ( 2 ) 257 - 262 2017.08

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

KUWATA Kazuaki, HANAYA Kengo, SUGAI Takeshi, SHOJI Mitsuru

Tetrahedron: Asymmetry 28 ( 7 ) 964 - 968 2017.07

Research paper (scientific journal), Accepted

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

FURUTA Miyu, HANAYA Kengo, SUGAI Takeshi, SHOJI Mitsuru

Tetrahedron 73 ( 16 ) 2316 - 2322 2017.04

Research paper (scientific journal), Accepted

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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".

NAGAI Toshiya,SAKURAI Saki,NATORI Naoki, HATAOKA Manaka, KINOSHITA Takako, INOUE Hiroyoshi, HANAYA Kengo, SHOJI Mitsuru, SUGAI Takeshi

Bioorganic & Medicinal Chemistry (Bioorganic and Medicinal Chemistry)  26 ( 7 ) 1304 - 1313 2017.04

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

YAMASHITA Yasunobu, BIARD Alan, HANAYA Kengo, SHOJI Mitsuru, SUGAI Takeshi

Bioscience, Biotechnology, and Biochemistry 81 ( 7 ) 1279 - 1284 2017.03

Research paper (scientific journal), Accepted

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

HANAYA Kengo, Matsumoto Kazuaki, Yokoyama Yuta, Kizu Junko, Shoji Mitsuru, Sugai Takeshi

CHEMICAL and PHARMACEUTICAL BULLETIN 65   194 - 199 2017

Research paper (scientific journal), Accepted

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

OKAZAKI Hayato, UEDA Yuji, HANAYA Kengo, SHOJI Mitsuru, SUGAI Takeshi

Heterocycles 95   862 - 871 2016.11

Research paper (scientific journal), Accepted

Preparation of (R)-3-Hydroxy-N-methylpiperidine, a Synthetic Key Intermediate of (R)-Mepenzolate, Based on the Lipase-Catalyzed Resolution of the Racemic Form

Yamashita Yasunobu, HANAYA Kengo, Shoji Mitsuru, Sugai Takeshi

Heterocycles  2016

Research paper (scientific journal), Accepted

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Development of a Novel Sulfonate Ester-Based Prodrug Strategy

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

Bioorganic & Medicinal Chemistry Letters 26   545 - 550 2016

Accepted

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

YAMASHITA Yasunobu, HANAYA Kengo, SHOJI Mitsuru, SUGAI Takeshi

CHEMICAL and PHARMACEUTICAL BULLETIN 64 ( 7 ) 961 - 965 2016

Research paper (scientific journal), Joint Work, Accepted

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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

YAMASHITA Yasunobu, KURIHARA Tohru, HORIGUCHI Takenobu, MIKI Atsushi, SHOJI Mitsuru, SUGAI Takeshi, HANAYA Kengo

Synthesis 48 ( 14 ) 2191 - 2200 2016

Research paper (scientific journal), Joint Work, Accepted

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