65(P-49) 抗マラリア活性物質Borrelidinの全合成(ポスター発表の部)

概要

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Borrelidin, a structurally unique 18-membered macrolide, was isolated from Streptomyces rochei in 1949 by Berger et al. as an antibiotic possessing anti-Borrelia activity. The absolute configuration was determined in 1989 through X-ray crystallography of a chiral solvate. Recently, we found that borrelidin shows potent antimalarial activity against chloroquine-resistant strains, both in vitro and in vivo. This biological profile, as well as borrelidin's structural complexity, prompted substantial effort toward the total synthesis of (-)-borrelidin. Three elegant total syntheses of borrelidin have been reported, by Morken et al., Hanessian et al. and Theodorakis et al. We report herein the stereocontrolled total synthesis of (-)-borrelidin. The best feature of our synthetic route is SmI_2-mediated intramolecular Reformatsky-type reaction to provide macrocyclization at C11-12 after esterification between two segments, and this strategy differs significantly from previous total syntheses. Other noteworthy features are as follows: regioselective methylation to construct the trisubstituted (Z)-olefin, directed hydrogenation, MgBr_2・Et_2O-mediated chelation-controlled allylation, and effective inversion of the C11 hydroxyl group.
天然有機化合物討論会の論文
2004-10-01