P-30 プロテインホスファターゼ阻害剤トウトマイシンの合成研究(ポスター発表の部)

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Tautomycin (1), isolated from a culture of Streptomyces spiroverticillatus, is an antifungal antibiotic. It also inhibits protein phosphatases, which are specifically inhibited by a famous tumor promoter, okadaic acid. We took notice of this interesting biological activity and its unique structure, and hence started synthetic studies on tautomycin. We herein describe our synthetic studies. 1) Synthesis of the C_1〜C_<16> subunit (6); We already reported synthesis of the C_1〜C_<16> subunit (6) at the 35th Symposium. Since then, yields of Julia olefination of 7 and 8 and subsequent reduction of 9 have been improved. 2) Synthesis of the C_<17>〜C_<26> subunit (5); The C_<17>〜C_<26> subunit was synthesized from the 2-deoxyglucose derivative (11). The key features of the transformation to 5 are summarized below. a) Selective mono-alkylation by the stannylene ketal, b) Synthesis of the terminal isopropyl group by formation of the cyclopropane ring and subsequent ring opening, c) Transformation to the acyclic intermediate, the dithiane (15) under the optimized conditions, d) Construction of the C_<19> and C_<20> asymmetric centers by Evans's aldol reaction. 3) Coupling of the C_1〜C_<16> subunit and the C_<17>〜C_<26> subunit; Reaction of the dianion of methylketone (5) and aldehyde (6) afforded the aldol adduct 23. It was acetylated and treated with DBU to afford 3. 4) Synthesis of C1'〜C7' subunit; The C1'〜C7' subunit was synthesized from itaconic acid (24). Synthesis of 27 was carried out by asymmetric reduction of the β-keto ester (25). Synthesis of 2 from 27 is now under investigation, and the total synthesis of tautomycin is now undergoing completion.
天然有機化合物討論会の論文
1994-09-20

P-30 プロテインホスファターゼ阻害剤トウトマイシンの合成研究(ポスター発表の部)

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