Marshall J A, Yanik M M
Department of Chemistry, McCormick Road, P.O. Box 400319, University of Virginia, Charlottesville, Virginia 22904, USA.
J Org Chem. 2001 Feb 23;66(4):1373-9. doi: 10.1021/jo0056951.
The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.
描述了互隔交链孢酚C1 - C21亚基的合成。该汇聚式路线使用了对映体富集的烯丙基锡烷和源自(S)-3-丁炔-2-醇甲磺酸酯的锌试剂。这些试剂与合适的醛片段反应，以高非对映选择性生成顺式和反式加合物。衍生的锂代炔烃逐步与一个CO等价物(MeONMe)₂C=O连接，得到一个中间体酮，经酸处理后转化为互隔交链孢酚的核心螺缩酮部分。通过将上述烯丙基锌试剂再次加入到螺缩酮醛中进行链延长，以高非对映选择性安装其余的立体中心。所得的高炔丙醇加合物通过炔烃的分子内硅氢化和衍生的五元硅氧烷的玉尾氧化转化为甲基酮。该酮被证明与钱伯林在之前互隔交链孢酚的全合成中使用的一个中间体相同。
