Synthesis of C13-C25 fragment of 24-demethylbafilomycin C(1) via diastereoselective aldol reactions of a ketone boron enolate as the key step.
Synthesis of C13-C25 fragment of 24-demethylbafilomycin C(1) via diastereoselective aldol reactions of a ketone boron enolate as the key step.
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DOI：
10.1021/jo070624o
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发表时间：
2007-05
期刊：
影响因子：
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通讯作者：
Yucui Guan;Jinlong Wu;Liang Sun;W. Dai
中科院分区：
文献类型：
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作者：
Yucui Guan;Jinlong Wu;Liang Sun;W. Dai
报道了24-demethylbafilomycin C1的C13-C25片段的高效合成。24-demethylbafilomycin C1是plecomacrolide家族的新成员，分离自Maytenus hookeri的共生微生物Streptomyces sp. CS发酵液。目标C13-C25片段具有5个氧合中心和3个甲基取代的立体中心。C17-C18 synaldol是由C15上被乙氧基和甲氧基乙氧基取代的手性醛用非对映比分别为95:5和83:17的乙基酮硼烯酸酯形成的。结果证实了酮体C22位置的立体化学对醛醇反应的非对映选择性起决定性作用。合成的C13-C25片段在C15处具有甲氧基乙酰氧基，被认为是构建24-去甲基巴菲霉素C1的16元环内酯的有用前体，通过甲氧基乙酸的醛醇缩合，然后通过二烯-烯RCM反应形成C12-C13双键。
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.