Guan Yucui, Wu Jinlong, Sun Liang, Dai Wei-Min
Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
J Org Chem. 2007 Jun 22;72(13):4953-60. doi: 10.1021/jo070624o. Epub 2007 May 23.
An efficient synthesis of the C13-C25 fragment is described for 24-demethylbafilomycin C1, a new member of the plecomacrolide family isolated from fermentation broth of Streptomyces sp. CS which is a commensal microbe of Maytenus hookeri. The targeted C13-C25 fragment possesses five oxygenated and three methyl-substituted stereogenic centers. It is obtained through formation of the C17-C18 syn aldol by using an ethyl ketone boron enolate with diastereomeric ratios of 95:5 and 83:17, respectively, for the chiral aldehydes substituted with acetoxy and methoxyacetoxy groups at C15. The results confirm the observation that the stereochemistry at C22 of the ketone is determinant to the diastereoselectivity of the aldol reaction. The synthesized C13-C25 fragment having a methoxyacetoxy group at C15 is considered as a useful precursor for construction of the 16-membered ring lactone of 24-demethylbafilomycin C1 through an aldol condensation of the methoxyacetate followed by formation of the C12-C13 double bond via a diene-ene RCM reaction.
描述了一种用于24-去甲基巴弗洛霉素C1的C13 - C25片段的有效合成方法，24-去甲基巴弗洛霉素C1是从链霉菌属CS的发酵液中分离出的plecomacrolide家族的新成员，链霉菌属CS是钩吻叶属的一种共生微生物。目标C13 - C25片段具有五个氧化的和三个甲基取代的立体中心。通过使用乙基酮硼烯醇盐形成C17 - C18顺式醛醇来获得该片段，对于在C15处被乙酰氧基和甲氧基乙酰氧基取代的手性醛，非对映体比例分别为95:5和83:17。结果证实了酮的C22处的立体化学对醛醇反应的非对映选择性起决定性作用这一观察结果。在C15处具有甲氧基乙酰氧基的合成C13 - C25片段被认为是通过甲氧基乙酸酯的醛醇缩合，然后通过二烯-烯复分解反应形成C12 - C13双键来构建24-去甲基巴弗洛霉素C1的16元环内酯的有用前体。
