Fukaya Keisuke, Yamaguchi Yu, Watanabe Ami, Yamamoto Hiroaki, Sugai Tomoya, Sugai Takeshi, Sato Takaaki, Chida Noritaka
Department of Applied Chemistry, Keio University, Yokohama, Japan.
Department of Pharmaceutical Science, Keio University, Tokyo, Japan.
J Antibiot (Tokyo). 2016 Apr;69(4):273-9. doi: 10.1038/ja.2016.6. Epub 2016 Feb 10.
The practical synthesis of the C-ring precursor of paclitaxel starting from 3-methoxytoluene is described. Lipase-catalyzed kinetic resolution of a substituted cyclohexane-1,2-diol, derived from 3-methoxytoluene in three steps, successfully afforded a desired enantiomer with >99% ee, which was transformed to a cyclohexenone. 1,4-Addition of a vinyl metal species, followed by Mukaiyama aldol reaction with formalin in the presence of a Lewis acid provided the known C-ring precursor of paclitaxel in a 10 g scale.
描述了从3-甲氧基甲苯出发实用合成紫杉醇C环前体的方法。通过脂肪酶催化对由3-甲氧基甲苯经三步衍生得到的取代环己烷-1,2-二醇进行动力学拆分，成功得到了对映体过量值（ee）>99%的所需对映体，该对映体被转化为环己烯酮。乙烯基金属物种进行1,4-加成，随后在路易斯酸存在下与福尔马林进行 Mukaiyama 羟醛反应，以10克规模提供了已知的紫杉醇C环前体。
