35 細胞毒性マクロリド配糖体、オーリサイド類の合成(口頭発表の部)

概要

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Aurisides A (1) and B (2) are macrolide glycosides isolated from Japanese sea hare Dolabella auricuralia, which exhibit cytotoxicity against HeLa S_3 cells with IC_<50> values of 0.17 and 1.2μg/mL, respectively. The main structural features of aurisides are a bromine-substituted conjugated diene, a 14-membered lactone, and a cyclic hemiacetal. We achieved the enantioselective synthesis of aurisides A and B by a convergent approach. The C1-C9 segment 4 was prepared from (R)-pantolactone using a reaction of dithiane carbanion with epoxide, stereoselective reduction of β-hydroxyketone with Me_4NBHOAc, and rhodium-catalyzed Reformatsky-type reaction as key steps. The C10-C17 segment 12 was synthesized from (R)-glycidyl trityl ether. The Nozaki-Hiyama-Kishi reaction between 4 and 12 and subsequent reactions including construction of bromine-substituted conjugated diene gave seco acid 10, which was converted into the aglycon (3) of aurisides by construction of the 14-membered lactone. The Mukaiyama glycosylation reaction of the aglycon 3 provided aurisides A (1) and B (2).
天然有機化合物討論会の論文
2006-09-15