P-48 イソマイグラスタチン及びドリゴシンBの合成研究(ポスター発表の部)

概要

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Isomigrastatin (1) was isolated from Streptomyces platensis. NRRL18993 and has a 12-membered macrolactone, a glutarimide side chain and four adjacent stereogenic centers including adjacent hydroxyl group and methoxy group (C8 and C9). Interestingly, Shen and co-workers demonstrated that Migrastatin (2), Dorrigocin A (3) and Dorrigocin B (4) are shunt metabolites of 1. 2 inhibits human tumor cell migration and 3, 4 reverse the Morphology of Ras-transformed NIH3T3 Fibroblasts. These interesting chemical structures and biological activities have attracted considerable attention to us, because we have developed that regio- and diastereoselective construction of acyclic stereochemistry using palladium-catalyzed hydrogenolysis and nucleophilic addition of methoxide to alkenyloxiranes, which is efficiently applicable to construction of C8-C9 stereogenic centers of 1 and 4. We have planned to synthesize 1 and 2 by coupling of the phosphoric ester 5 with the readily available glutalimide 6 and the sulfone 7, using Horner-Wadsworth-Emmons reaction or Julia-Kocienski reaction. In this symposium we would like to describe the synthesis of the key intermediate 5 carried out starting with 8 in 21 steps, using palladium-catalyzed methodologies for the acyclic stereoselections as key reactions.
天然有機化合物討論会の論文
2008-09-01