36 立体特異的鎖状分子構築法を機軸とする天然物合成(口頭発表の部)

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We recently developed a novel acyclic stereocontrol based on the stereospecific methylation of γ,δ-epoxy acrylates with trimethylaluminum in the presence of water by which both anti and syn compounds can be highly stereoselectively synthesized from trans- and cis-γ,δ-epoxy acrylates, respectively. We report here stereospecific internal alkylation of terminal epoxides and stereospecific construction of asymmetric quaternary carbons via γ,δ-epoxy acrylates. We also report synthetic studies toward total synthesis of a marine natural product discodermolide and epothilone based on the above methodologies. Stereospecific Internal Alkylation of Terminal Epoxides Regio- and stereoselective internal alkylation of terminal epoxides has little been known. We designed such a reaction using γ,δ-epoxy acrylates with trimethylaluminum. The reaction of terminal γ,δ-epoxy acrylates 1 and 2, easily prepared from D-mannitol, with excess trimethylaluminum in the presence of water proceeded regiospecifically at the γ-position to give 3 and 4 as the sole product, respectively, with maintenance of optical integrity. Stereospecific Construction of Asymmetric Quaternary Carbons via γ-Alkyl-γ,δ-epoxy Acrylates We found that the reaction of γ-alkyl-γ,δ-epoxy acrylates with trialkylaluminum and water occurs regio- and stereo-specifically at the γ-position as well yielding an asymmetric quaternary carbon. Thus treatment of 5 and 6 with excess trimethylaluminum in the presence of water gave 7 and 8 as a single product, respectively, in which a methyl group was stereospecifically introduced at the γ-position with net inversion of configuration. Synthetic Studies on Discodermolide and Epothilone We set out synthesis of discodermolide having potent immunosuppressive activity based on the above stereospecific acyclic stereocontrol. Discodermolide was devided into three segments in which the segment B having three contiguous chiral centers and the segment C possessing five chiral centers have been highly stereoselectively synthesized as shown in Schemes 5 and 6, respectively. Stereoselective synthesis of the C1-C9 segment of epothilone having potent anticancer activity was also carried out as shown in Scheme 7 in which five asymmetric centers was highly stereoselectively constructed by repeating the above methylation reaction.
天然有機化合物討論会の論文
1998-08-31

36 立体特異的鎖状分子構築法を機軸とする天然物合成(口頭発表の部)

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