P-57 ヒストン脱アセチル化酵素阻害物質スピルコスタチンAの合成研究(ポスター発表の部)

概要

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Spiruchostatin A (1), isolated from the Pseudomonas sp., is a potent histone deacetylase inhibitor. Therefore, this natural product is anticipated to be a promising new agent for cancer chemotherapy. The attractive biological activities and unique structural features prompted us to undertake the total syntheses of 1. We envisioned that 1 would be elaborated through the disulfide bond formation of 2 possessing the requisite carbon framework, functional groups, and asymmetric carbons. Macrocyclic compound 2 can be synthesized through macrolactonization of seco-acid 3. We initially pursued the synthesis of the segments 4 and 5, which were then subjected to the amide coupling reaction. The amide coupling reaction proceeded smoothly, and desired product 17 was obtained. We next conducted the construction of the macrolactone ring. After deprotection of the PMB group, desired product 18 was obtained. However, hydrolysis of isopropyl ester moiety provided complex reaction mixture. Next, we conducted esterification reaction between segment 19 and 20. Estericication reaction using MNBA afford desired liner tripeptide 21. Disulfide bond formation using iodine furnished 22. After removal of Boc group, hydrolysis of methyl ester moiety gave 24. Further investigation toward the total synthesis of 1 is now in progress.
天然有機化合物討論会の論文
2006-09-15