Progress on the Stereoselective Synthesis of Chiral Molecules Based on Metal-Catalyzed Dynamic Kinetic Resolution of Alcohols with Lipases

Abstract

Metal/lipase-combo catalyzed dynamic kinetic resolution (DKR) of racemic chiral alcohols is a general and practical process to obtain the corresponding enantiopure esters R with quantitative conversion. The use of known Ru-catalysts as well as newly developed homogeneous and heterogeneous metal catalysts (Fe, V) contributed to make the DKR process more sustainable and to expand the substrate scope of the reaction. In addition to classical substrates, challenging allylic alcohols, tertiary alcohols, C1-and C2-symmetric biaryl diols turned out to be competent substrates. Synthetic utility further emerged from the integration of this methodology into cascade reactions leading to linear/cyclic chiral molecules with high ee through the formation of multiple bonds, in a one-pot procedure.

Lipase/H2SO4‐Cocatalyzed Dynamic Kinetic Resolution of Alcohols in Pickering Emulsion

“…[1][2][3] In particular, the DKR of alcohols has been intensively studied because alcohols play a pivotal role in the synthesis of various biologically active compounds such as natural products and pharmaceuticals. [4][5][6] Lipase-catalyzed enantioselective acylation in organic solvents is a well-established method for the DKR of various alcohols because of its high enantioselectivity and wide substrate scope. [7] Typical racemization for DKR include catalysis via redox pathways [8][9][10][11][12][13] and carbocation intermediates.…”

“…Chemoenzymatic dynamic kinetic resolution (DKR) combines enzymatic kinetic resolution (KR) and rapid racemization of the starting materials in a one‐pot system to obtain optically active compounds in quantitative yields [1–3] . In particular, the DKR of alcohols has been intensively studied because alcohols play a pivotal role in the synthesis of various biologically active compounds such as natural products and pharmaceuticals [4–6] . Lipase‐catalyzed enantioselective acylation in organic solvents is a well‐established method for the DKR of various alcohols because of its high enantioselectivity and wide substrate scope [7]…”

Biocatalytic asymmetric synthesis of secondary allylic alcohols using Burkholderia cepacia lipase immobilized on multiwalled carbon nanotubes

“…Enantiopure allylic alcohols are versatile building blocks for asymmetric synthesis and exist in a wide range of natural products. Their utility has been largely demonstrated in a variety of organic transformations, including the formation of carbon–carbon bonds and the addition of several functional groups into the double bond, incorporating other stereocenters through reactions of hydrogenation, epoxidation, and hydroboration, such as Simmons–Smith reaction 1–8 . Furthermore, optically active allylic alcohols can serve as building blocks in the synthesis of chiral lactones, such as 4‐hydroxy‐5‐6‐dihydropyrone, which has inhibitory activity against the HIV protease 9,10 .…”

“…Their utility has been largely demonstrated in a variety of organic transformations, including the formation of carbon-carbon bonds and the addition of several functional groups into the double bond, incorporating other stereocenters through reactions of hydrogenation, epoxidation, and hydroboration, such as Simmons-Smith reaction. [1][2][3][4][5][6][7][8] Furthermore, optically active allylic alcohols can serve as building blocks in the synthesis of chiral lactones, such as 4-hydroxy-5-6-dihydropyrone, which has inhibitory activity against the HIV protease. 9,10 Beyond this, some allylic alcohols are used in the synthesis of enantiomerically pure hydroxy lactones, which exhibited high antifeedant activity against insects.…”

Research Progress of Chiral MOFs in Chiral Resolution

“…夏凉 等：手性 MOFs 在手性拆分中的研究进展 http://www.chemscieng.com 1 引言 手性化合物，即拥有相同的分子式而在立体空间结 构上互为镜像对称的对映异构体，它们普遍存在于自然 界并与人类的生活息息相关 [1,7]。上个世纪 60 年代一 种镇静剂--沙利度胺--引起了世界对对映异构体 不同药理作用及其分离的关注， 因为 R-沙利度胺是一种 有效的止吐药，而 S-沙利度胺则会导致严重的生理缺陷。 此后对手性药物、手性农药等的研究中也发现对映异构 体生理药理的活性存在很大的差异。美国食品药品管理 局对手性药物的上市申报中提出必须指明这两种对映 体的生理活性要求，对手性化合物的生产和使用也需要 对其纯度进行分析报道。因此，开发有利的制备方法以 获得更高纯度的单一对映体是至关重要的。 迄今为止，光学纯手性化合物的制备主要集中在 以下三大方面： 手性源合成法 [2]， 不对称合成法 [3,4]， 手性拆分法。手性源合成法和不对称合成法由于方法 步骤繁琐且难度大，重金属残留等缺陷也限制了它们 的应用。手性拆分是一种基于不同对映体的理化性质 的差异将外消旋化合物拆分获得光学纯化合物的方法， 包括化学拆分法 [8]、色谱拆分法 [9]、生物转化法 [10]、 固相萃取拆分法 [11]、结晶拆分法[5]和膜拆分法 [12]等。 手性拆分具有可操作和实用性强、重现性好以及环境 友好等优点通常可以得到较高产量的对映体。据统计， 目前大部分的手性药物经由外消旋体拆分获得[6]。 手性化合物的拆分需要借助手性选择剂来完成。 手性选择剂在面对外消旋体时可以通过与之作用形成 瞬时非对映体进而将对映异构体之间的差异增大来完 成选择性识别，从而实现拆分。目前已经有多种手性 选择剂被报道并得到了很好的效果：手性金属有机框 架(MOFs) [13]、环糊精及其衍生物 [14]、蛋白质 [15] 和手性冠醚 [16,17]等。…”