23 スウィンホライドAおよびその関連化合物の合成研究(口頭発表の部)

抄録

Swinholide A (1), isolated from a sponge of the genus Theonella swinhoei, is a unique 44-membered dimeric macrolide and exhibits potent cytotoxicity against KB and L1210 tumor cells in vitro. We now report the synthetic studies of swinholide A (1) and the related compounds. 1) Synthesis of the C-11〜C-23 Segment Aldol condensation of aldehyde 12 (2 eq) and MeNO_2 (1 eq) in the presence of Et_3N under super high pressure (11Kb) produced diol 13 effectively. 13 was converted into 19 via an epimerization of ketone 14. On treatment of 19 with BH_3・Me_2S, hydroboration of exomethylene and successive reductive cleavage of p-methoxybenzylidene acetal took place stereoselectively producing diol 20. Treatment of lactone 24 with LDA, MeI gave a single α-methyl lactone 25 which was converted into aldehyde 27. Aldol condensation of 27 and 28 produced 29 as a single product which was transformed into aldehyde 31. 2) Synthesis of the C-24〜C-31 Segment Ketone 35 was synthesized starting from methyl (S)-hydroxy butyrate (32) via lactone 34. Reduction of 35 with LiAlH_4 followed by methylation afforded α-methoxy compound 36 exclusively. Treatment of 36 with allyltrimethylsilane in the presence of BF_3・Et_2O gave only β-allyl compound 37 which was converted into 41 via ester 39. 3) Synthesis of the C-11〜C-31 Segment Aldol condensation of aldehyde 31 and 41 gave a single product 42 which was converted into alcohol 44. Synthesis of 1 and 2 from 44 is now in progress.