Papers - Suenaga, Kiyotake

Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides

Takamura, Hiroyoshi, Kikuchi, Takahiro, Iwamoto, Kohei, Nakao, Eiji, Harada, Naoki, Otsu, Taichi, Endo, Noriyuki, Fukuda, Yuji, Ohno, Osamu, Suenaga, Kiyotake, Guo, Yue-Wei, Kadota, Isao

Journal of Organic Chemistry 83 ( 18 ) 11028 - 11056 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022-3263

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Isolation of Jahanene and Jahanane, and Total Synthesis of the Jahanyne Family

Iwasaki, Arihiro, Fujimura, Haruka, Okamoto, Shinichiro, Kudo, Takafumi, Hoshina, Shizuka, Sumimoto, Shimpei, Teruya, Toshiaki, Suenaga, Kiyotake

Journal of Organic Chemistry 83 ( 17 ) 9592 - 9603 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022-3263

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ISOLATION AND IDENTIFICATION OF A GROWTH INHIBITORY SUBSTANCE FROM HELIOTROPIUM INDICUM L.

Chaipon, Sirinapa, Suwitchayanon, Prapaipit, Iwasaki, Arihiro, Suenaga, Kiyotake, Kato-Noguchi, Hisashi

Acta Biologica Hungarica 69 ( 3 ) 259 - 269 2018.09

Research paper (scientific journal), Accepted,  ISSN  0236-5383

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Izenamides A and B, Statine-Containing Depsipeptides, and an Analogue from a Marine Cyanobacterium

Kanamori Yuki, Iwasaki Arihiro, Sumimoto Shimpei, Matsubara Teruhiko, Sato Toshinori, Suenaga Kiyotake

Journal of Natural Products 81 ( 7 ) 1673 - 1681 2018.07

Accepted,  ISSN  0163-3864

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<p>Izenamides A, B, and C (1-3), new linear depsipeptides, were isolated from a taxonomically distinct marine cyanobacterium. Izenamides A and B contain a statine moiety [(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid] and inhibited the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10 μM.</p>

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Plant growth inhibitory activity and active substances with allelopathic potential of cogongrass (Imperata cylindrica) rhizome

Suzuki Masahiko, Tominaga Tohru, Ohno Osamu, Iwasaki Arihiro, Suenaga Kiyotake, Kato-Noguchi Hisashi

Weed Biology and Management 8 ( 2 ) 92 - 98 2018.06

Accepted,  ISSN  1444-6162

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<p>Cogongrass (Imperata cylindrica [L.] Raeusch.) is a perennial rhizomatous grass that belongs to the Poaceae and is widely distributed in tropical, subtropical and temperate regions over the world. The grass is strongly invasive and is suggested to have allelopathic potential. However, limited information is available on allelopathic substances in cogongrass rhizomes. Therefore, the allelopathic potential and substances in cogongrass rhizomes were investigated. The extracts of cogongrass rhizomes inhibited the root and shoot growth of barnyard grass, ryegrass, timothy, cress, lettuce and alfalfa. After bioassay-guided separations of the extracts, four growth inhibitory substances, 5-methoxyflavone, 5,2'-dimethoxyflavone, methyl caffeate and abscisic acid, were isolated. 5-Methoxyflavone, 5,2'-dimethoxyflavone and methyl caffeate significantly inhibited the root and shoot growth of cress at concentrations of ≥0.03-0.3m mol L^-1 and their concentrations required for 50% growth inhibition were 0.079-0.24, 0.23-1.1 and 0.59-0.88m mol L^-1, respectively. The other isolated substance, abscisic acid, has been reported to have strong growth inhibitory activity. Its concentrations required for 50% growth inhibition on cress were 0.31-0.61μ mol L^-1. The present study suggests that cogongrass rhizomes might have allelopathic potential and that those four substances might contribute to that potential.</p>

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Evaluation of phytotoxic activity of leaf and stem extracts and identification of a phytotoxic substance from Caesalpinia mimosoides Lamk.

Boonmee Sutjaritpan, Iwasaki Arihiro, Suenaga Kiyotake, Kato-Noguchi Hisashi

Theoretical and Experimental Plant Physiology 30 ( 2 ) 129 - 139 2018.06

Accepted

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<p>Caesalpinia mimosoides (Fabaceae) has been used as a folk medicine and reported to have pharmacological properties. However, the phytotoxicity of C. mimosoides has not yet been studied. Therefore, the phytotoxic activity of C. mimosoides leaf and stem extracts was evaluated against the growth of dicotyledonous and monocotyledonous plants. Aqueous methanol extracts of C. mimosoides leaves and stems exhibited inhibitory effects on the growth of all the test plants. The growth of the test plants decreased with the increase of concentrations of the extracts. Comparison of the concentrations required for 50% growth inhibition (I₅₀ values) indicates that the leaf extracts had more inhibitory effects than the stem extracts. Thus, the active substances in the leaf extracts were purified using column chromatographic separations and a growth inhibitory substance was isolated and identified as methyl gallate by using spectral analysis. This study reports the first isolation of methyl gallate in C. mimosoides leaves. Methyl gallate at 10 mM completely inhibited the growth of cress shoots and inhibited its roots by 4.7% of control growth. At the same concentration, the shoots and roots of barnyard grass were inhibited by 84.2 and 1.7% of control growth, respectively. I₅₀ values of methyl gallate for the growth of cress and barnyard grass ranged from 2.3 to 2.9 and 0.3 to 30.5 mM, respectively. The results suggest that methyl gallate may be responsible for the phytotoxic effects of C. mimosoides.</p>

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Ypaoamides B and C, Linear Lipopeptides from an Okeania sp. Marine Cyanobacterium

Sueyoshi Kosuke, Yamada Miki, Yamano Aki, Ozaki Kaori, Sumimoto Shimpei, Iwasaki Arihiro, Suenaga Kiyotake, Teruya Toshiaki

Journal of Natural Products 81 ( 4 ) 1103 - 1107 2018.04

Accepted,  ISSN  0163-3864

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<p>Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.</p>

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Total synthesis of janadolide

Ojima Daisuke, Mine Hitomi, Iwasaki Arihiro, Suenaga Kiyotake

Tetrahedron Letters 59 ( 14 ) 1360 - 1362 2018.04

Accepted,  ISSN  0040-4039

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<p>The first total synthesis of janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, is described. The synthesis of an unsaturated hydroxycarboxylic acid was effected via the lithiation of vinyl iodide followed by addition to a Weinreb amide with a tert-butyl group and stereoselective 1,2-reduction. The cyclic structure was constructed by macrolactamization at the amide bond between the proline moiety and fatty acid moiety.</p>

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Caldorin, a new polyketide from the marine cyanobacterium Caldora penicillata

Shiota Ikuma, Iwasaki Arihiro, Sumimoto Shimpei, Tomoda Hiroshi, Suenaga Kiyotake

Tetrahedron Letters 59 ( 13 ) 1261 - 1263 2018.03

Accepted,  ISSN  0040-4039

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<p>A new polyketide with a cis-fused decalin ring scaffold, caldorin, was isolated from the marine cyanobacterium Caldora penicillata. The gross structure and relative configuration were elucidated by spectroscopic analyses. We also clarified that caldorin is a weak SOAT inhibitor and moderate osteoblast differentiation inhibitor. On the other hand, caldorin did not exhibit cytotoxicity against either HeLa or HL60 cells.</p>

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Design, synthesis and anti-malarial activities of synthetic analogs of biselyngbyolide B, a Ca²⁺ pump inhibitor from marine cyanobacteria

Sato E., Morita M., Ogawa H., Iwatsuki M., Hokari R., Ishiyama A., Ōmura S., Iwasaki A., Suenaga K.

Bioorganic and Medicinal Chemistry Letters (Bioorganic and Medicinal Chemistry Letters)  28 ( 3 ) 298 - 301 2018.02

ISSN  0960894X

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© 2017 Elsevier Ltd Biselyngbyaside, an 18-membered macrolide glycoside from marine cyanobacteria, and its derivatives are known to be sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors. Recently, a SERCA orthologue of the malaria parasite, PfATP6, has attracted attention as a malarial drug target. To provide a novel drug lead, we designed new synthetic analogs of biselyngbyolide B, the aglycone of biselyngbyaside, based on the co-crystal structure of SERCA with biselyngbyolide B, and synthesized them using the established synthetic route for biselyngbyolide B. Their biological activities against malarial parasites were evaluated.

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Design, synthesis and anti-malarial activities of synthetic analogs of biselyngbyolide B, a Ca²⁺ pump inhibitor from marine cyanobacteria

Sato Eisuke, Morita Maho, Ogawa Haruo, Iwatsuki Masato, Hokari Rei, Ishiyama Aki, Omura Satoshi, Iwasaki Arihiro, Suenaga Kiyotake

Bioorganic and Medicinal Chemistry Letters 28 ( 3 ) 298 - 301 2018.01

Accepted,  ISSN  0960-894X

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<p>Biselyngbyaside, an 18-membered macrolide glycoside from marine cyanobacteria, and its derivatives are known to be sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) inhibitors. Recently, a SERCA orthologue of the malaria parasite, PfATP6, has attracted attention as a malarial drug target. To provide a novel drug lead, we designed new synthetic analogs of biselyngbyolide B, the aglycone of biselyngbyaside, based on the co-crystal structure of SERCA with biselyngbyolide B, and synthesized them using the established synthetic route for biselyngbyolide B. Their biological activities against malarial parasites were evaluated.</p>

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Identification of 6,7-dimethoxychromone as a potent allelochemical from jatropha podagrica

Boonmee S., Iwasaki A., Suenaga K., Kato-Noguchi H.

Natural Product Communications (Natural Product Communications)  13 ( 11 ) 1515 - 1518 2018

ISSN  1934578X

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© 2018 Natural Product Incorporation. Jatropha podagrica Hook. is cultivated as an ornamental plant and is also used in traditional medicine. The species has various pharmacological properties, but it has not yet been investigated for any potential allelopathic activity and allelopathic substances. In this study, an allelopathic active substance was isolated from an aqueous methanol extract of J. podagrica leaves through chromatography and reverse-phase HPLC. The substance was characterized as 6,7- dimethoxychromone by spectral analysis. 6,7-Dimethoxychromone significantly inhibited the shoots and roots of cress at concentrations greater than 0.3 mM. The concentrations required of 6,7-dimethoxychromone for 50% growth inhibition of cress shoots and roots were 0.95 and 0.83 mM, respectively. The inhibitory activity against the seedling growth of cress indicates that 6,7-dimethoxychromone may contribute to the allelopathic effects and may be responsible for the allelopathic activity in J. podagrica. This report is the first on the allelopathic activity of 6,7-dimethoxychromone as an allelopathic substance from J. podagrica.

Total Synthesis of Kanamienamide and Clarification of Biological Activity

Ojima Daisuke, Iwasaki Arihiro, Suenaga Kiyotake

Journal of Organic Chemistry 82 ( 23 ) 12503 - 12510 2017.12

Accepted,  ISSN  0022-3263

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<p>The total synthesis of kanamienamide, an enamide with an enol ether and an 11-membered macrolactone of marine origin, was achieved. The synthesis features the construction of an enamide adjacent to an enol ether by Buchwald amidation and an 11-membered ring by Mitsunobu lactonization. In addition, on the basis of the biological assay of synthetic 1, we clarified that kanamienamide (1) was not an apoptosis-like cell death inducer, as reported in the isolation paper, and revealed its real biological activity as a necrosis-like cell death inducer.</p>

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Total Synthesis of Kanamienamide and Clarification of Biological Activity

Ojima Daisuke, Iwasaki Arihiro, Suenaga Kiyotake

Journal of Organic Chemistry 82 ( 23 ) 12503 - 12510 2017.12

Accepted,  ISSN  0022-3263

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<p>The total synthesis of kanamienamide, an enamide with an enol ether and an 11-membered macrolactone of marine origin, was achieved. The synthesis features the construction of an enamide adjacent to an enol ether by Buchwald amidation and an 11-membered ring by Mitsunobu lactonization. In addition, on the basis of the biological assay of synthetic 1, we clarified that kanamienamide (1) was not an apoptosis-like cell death inducer, as reported in the isolation paper, and revealed its real biological activity as a necrosis-like cell death inducer.</p>

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2-Methoxystypandrone, a potent phytotoxic substance in Rumex maritimus L

Islam Md Shafiqul, Iwasaki Arihiro, Suenaga Kiyotake, Kato-Noguchi Hisashi

Theoretical and Experimental Plant Physiology 29 ( 4 ) 195 - 202 2017.12

Accepted

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<p>Herbicide use has raised concerns which results in the need to find an alternative approach, using natural methods, of controlling weeds. Phytotoxic substances released from plants have been used to manage weeds biologically. Rumex maritimus, belonging to the Polygonaceae family, is well known to have a wide range of biological properties. However, the phytotoxic properties of R. maritimus is not well documented. Thus, we conducted an investigation into the phytotoxic potential of R. maritimus and attempted to find out its phytotoxic substances. Leaf, stem and root extracts of R. maritimus exhibited a strong inhibitory effects on root and shoot length of Lactuca sativa L., Medicago sativa L., Lolium multiflorum Lam., Phleum pratense L. With increasing extract concentration, inhibition increased. One substance, 2-methoxystypandrone, was purified after a series of chromatography and characterized by spectral data. 2-Methoxystypandrone reduced the seedling length of Lepidium sativum at concentration ≥ 3 μM. The required 50% growth inhibition concentration of Lepidium sativum seedling for 2-methoxystypandrone was ranged 5.8–11.8 μM. Therefore, it is suggested that the phytotoxic effects of R. maritimus on the test plants may be caused due to the presence of 2-methoxystypandrone.</p>

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Three new malyngamides from the marine cyanobacterium moorea producens

Sueyoshi Kosuke, Yamano Aki, Ozaki Kaori, Sumimoto Shimpei, Iwasaki Arihiro, Suenaga Kiyotake, Teruya Toshiaki

Marine Drugs 15 ( 12 ) 367 (13 pages) 2017.12

ISSN  1660-3397

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<p>Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK).</p>

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Two allelopathic substances from Paspalum commersonii Lam.

Zaman Farhana, Iwasaki Arihiro, Suenaga Kiyotake, Kato-Noguchi Hisashi

Acta Agriculturae Scandinavica Section B: Soil and Plant Science 68 ( 4 ) 342 - 348 2017.11

Accepted,  ISSN  0906-4710

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<p>Paspalum commersonii (Poaceae) is a herbaceous perennial weed distributed in the tropics and subtropics regions and grows mainly in the moist, or even flooded soil. It often appears in the rice field as a competitive weed and difficult to manage. Its strong competitive nature indicates possible allelopathic potential of P. commersonii. However, no studies have been found yet on the allelopathic activity of P. commersonii. Thus, we investigated the allelopathic potential of this weed and determined its allelopathic substances. Aqueous methanol extracts of P. commersonii showed concentration-dependent inhibitory activity on the seedling growth of cress, alfalfa, rapeseed, lettuce, barnyard grass, foxtail fescue, Italian ryegrass, and timothy. Two substances were isolated through bioassay-guided fractionation and their structures were determined through spectral data as dehydrovomifoliol and loliolide. Dehydrovomifoliol and loliolide started inhibiting the shoot and root growth of cress at concentrations greater than 3 and 0.03 mM, respectively. The concentrations required for 50% inhibition (I₅₀) of cress shoot and root growth were 3.34 and &gt;3.50 mM for dehydrovomifoliol and 0.04 and 0.05 mM for loliolide, respectively. These results indicate that both substances may affect the inhibitory activity of P. commersonii.</p>

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Involvement of allelopathy in inhibition of understory growth in red pine forests

Kato-Noguchi Hisashi, Kimura Fukiko, Ohno Osamu, Suenaga Kiyotake

Journal of Plant Physiology 218   66 - 73 2017.11

Accepted,  ISSN  0176-1617

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<p>Japanese red pine (Pinus densiflora Sieb. et Zucc.) forests are characterized by sparse understory vegetation although sunlight intensity on the forest floor is sufficient for undergrowth. The possible involvement of pine allelopathy in the establishment of the sparse understory vegetation was investigated. The soil of the red pine forest floor had growth inhibitory activity on six test plant species including Lolium multiflorum, which was observed at the edge of the forest but not in the forest. Two growth inhibitory substances were isolated from the soil and characterized to be 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid. Those compounds are probably formed by degradation process of resin acids. Resin acids are produced by pine and delivered into the soil under the pine trees through balsam and defoliation. Threshold concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid for the growth inhibition of L. multiflorum were 30 and 10 μM, respectively. The concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid in the soil were 312 and 397 μM, respectively, which are sufficient concentrations to cause the growth inhibition because of the threshold. These results suggest that those compounds are able to work as allelopathic agents and may prevent from the invasion of herbaceous plants into the forests by inhibiting their growth. Therefore, allelopathy of red pine may be involved in the formation of the sparse understory vegetation.</p>

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Total Synthesis of Biselyngbyaside

Sato Eisuke, Sato Miho, Tanabe Yurika, Nakajima Naoya, Ohkubo Akifumi, Suenaga Kiyotake

Journal of Organic Chemistry 82 ( 13 ) 6770 - 6777 2017.07

Accepted,  ISSN  0022-3263

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<p>The first total synthesis of biselyngbyaside, an 18-membered macrolide glycoside, was achieved. The glycoside bond was introduced using the Schmidt method before construction of the 18-membered ring due to the instability of the conjugated diene and the β-hydroxy ester moiety. The macrolactone ring was constructed using the Mitsunobu reaction followed by intramolecular the Stille coupling reaction.</p>

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Myrislignan, a growth inhibitor from the roots of citronella grass

Suwitchayanon Prapaipit, Suenaga Kiyotake, Iwasaki Arihiro, Kato-Noguchi Hisashi

Natural Product Communications 12 ( 7 ) 1077 - 1078 2017.07

Accepted,  ISSN  1934-578X

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<p>A phytotoxic compound was isolated from the root extracts of Cymbopogon nardus by bioassay-guided purification and characterized to be myrislignan. Myrislignan significantly inhibited seedling growth of cress at a concentration greater than 100 μM (p &lt; 0.05). The concentrations required for 50% growth inhibition of myrislignan on hypocotyl and root growth of cress were 429 μM and 517 μM, respectively. The inhibition on seedling growth indicated that myrislignan had a phytotoxic activity and may contribute to the phytotoxic effect of C. nardus.</p>