著者

中村 優一 馬岡 秀陽 上岡 麗子 池田 剛 塚本 佐知子

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.52, pp.505-510, 2010

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We reported the structures and biosynthetic experiments of prenylated indole alkaloids, notoamides, which isolated from a marine-derived fungus Aspergillus sp. Among them, notoamides A and B (1 and 2) and stephacidin A (6) contain a bicyclo[2.2.2]diazaoctane ring, which is proposed to be constructed from notoamice E (8) by the intramolecular Diels-Alder (IMDA) reaction. We made a feeding experiment of ^<13>C-labeled-8 in the minimum medium. Contrary to our expectaton, compounds containing a bicyclo ring were not obtained at all. This result suggested that the formation of a pyrane ring would be constructed after the formation of the bicyclo ring. Then, we made a feeding experiment of ^<13>C, ^<15>N-labeled-7, which lacks a pyrane ring in 6. As the result, a pinacol-type rearrangement of the isoprenyl group in 7 occurred to give 11 and 12, and no metabolite containing a bicyclo ring was afforded. Now, feeding experiments of ^<13>C, ^<15>N-labeled-11 and -12 are in progress. Nortoamides O-R (14-17) were isolated from the same extract of the fungus, which yielded other notoamides. Notoamide O (14) possesses a novel hemiacetal/hemiaminal ether functionality hitherto unknown among this family of prenylated indole alkaloids. The structure represents an unusual branc point for the oxidative modification of other members in the family of prenylated indole alkaloids in the biogenetic pathway.

著者

中村 優一 加藤 光 塚本 佐知子

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.53, pp.421-426, 2011

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In our laboratory, we search for drug leads from marine sponge, ascidian and fungus. The extract of the ascidian Didemnum sp., which collected in Indonesia in 2006, showed anti-fungal activity and inhibitory activity of p53-Mdm2 complex formation. p53, tumor suppressor, protein induced growth arrest and apoptosis, and Mdm2 is an E3 for p53 protein. Therefore, inhibition of p53-Mdm2 complex formation is a promising approach for treatment of cancer. Twelve new serinolipids, 1-12 were isolated from Indonesian ascidian Didemnum sp. 1D and 2D NMR spectrum and MS spectrum analysis was revealed the structures of these compounds possessing a 6,8-dioxabicyclo[3.2.1]octane ring, which was appeared in didemniserinolipid A, a glycerophosphocholine moiety and a serinol moiety containing sulfate. Compounds 1-12 demonstrated inhibition of p53-Mdm2 complex formation. Compounds 1 and 5 were the most potent inhibitors with an IC^<50> value of 2.0 μM, while compounds -2 and 10 exhibited weak inhibitors with IC^<50> values of 53 and 55 μM, respectively.

著者

塚本 佐知子

出版者

北海道大学

巻号頁・発行日

1988

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博士論文

著者

塚本 佐知子

出版者

公益社団法人日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.31, no.12, 1995-12-01