Paterson Ian, Lyothier Isabelle
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
J Org Chem. 2005 Jul 8;70(14):5494-507. doi: 10.1021/jo050481a.
[structure: see text] A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still-Gennari-type HWE olefination reaction between advanced C1-C8 beta-ketophosphonate 61 and C9-C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1-C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride.
[结构：见正文] 复杂聚酮化合物discodermolide的一种新型全合成已完成，该化合物是一种有前景的源自海洋海绵的抗癌剂，21步线性反应的总产率为11.1%。这种第三代方法的特点是在高级C1-C8 β-酮膦酸酯61和C9-C24醛7之间进行了前所未有的Still-Gennari型HWE烯化反应，以10:1的选择性引入了(8Z)-烯烃。C1-C8亚基61中发现的立体四元组是通过酮(S)-8和3-苄氧基丙醛之间高度非对映选择性的硼介导的羟醛反应/原位还原建立的。(7S)-构型是通过用K-Selectride还原烯酮73来安装的。
