Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Chair of Industrial Organic Chemistry and Biotechnology, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany.
Chemistry. 2022 Oct 26;28(60):e202202437. doi: 10.1002/chem.202202437. Epub 2022 Oct 7.
Natural lipases typically recognize enantiomers of alcohols based on the size differences of substituents near the carbinol moiety and selectively react with the R enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only R enantiomers. We report herein a method for obtaining S enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols by using a well-known R-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety. We have already reported R-selective DKR of the corresponding propargyl alcohols without substituents on the ethynyl terminal carbon, and the presence of an easily removable silyl group has enabled us to produce both enantiomers of propargyl alcohols in high chemical yields and with high enantiomeric excess. In addition, immobilization of the lipase on Celite was found to be important for achieving a high efficiency of the DKR.
天然脂肪酶通常根据靠近羟甲基部分的取代基的大小差异来识别醇的对映异构体，并选择性地与仲醇的 R 对映异构体反应。因此，脂肪酶催化的外消旋仲醇的动态动力学拆分（DKR）仅产生 R 对映异构体。我们在此报告了一种通过使用众所周知的 R 选择性荧光假单胞菌脂肪酶与外消旋催化剂 VMPS4 组合，从仲 3-（三烷基硅基）炔丙醇进行 DKR 来获得 S 对映异构体的方法，其中硅烷基反转了羟甲基部分附近取代基的大小关系。我们已经报道了相应的无末端炔碳原子取代基的炔丙醇的 R 选择性 DKR，并且易于去除的硅烷基的存在使我们能够以高化学产率和高对映过量生产炔丙醇的两种对映异构体。此外，发现将脂肪酶固定在 Celite 上对于实现 DKR 的高效率非常重要。
