Odman Peter, Wessjohann Ludger A, Bornscheuer Uwe T
Department of Technical Chemistry and Biotechnology, Institute of Chemistry and Biochemistry, Greifswald University, Soldmannstrasse 16, D-17487 Greifswald, Germany.
J Org Chem. 2005 Nov 11;70(23):9551-5. doi: 10.1021/jo051661n.
[Reaction: see text]. Acyloins (alpha-hydroxy ketones) are important building blocks in organic synthesis, e.g., for the total synthesis of epothilones. Optically pure acyloins can be obtained by lipase-catalyzed kinetic resolution (KR) of the racemate with, for example, Burkholderia cepacia lipase, but this process suffers from a yield limitation of 50%. To devise a dynamic kinetic resolution (DKR), we studied the racemization of two different acyloins and corresponding esters with various amine bases and ion exchangers. No combination of base and solvent was found that could selectively racemize the acyloin or corresponding ester under the conditions needed for a DKR. In contrast to bases, acidic resins (ARs) were found to racemize the acyloins selectively in n-hexane and in water. Unfortunately, the AR deactivated the lipase, preventing a one-pot DKR. Minor side reactions involving the AR, the substrate acyloin, and the vinyl ester acyl donor were also observed. However, an efficient DKR was made possible by the spatial separation of lipase and ion exchanger, with enzymatic transesterification and AR-catalyzed racemization taking place simultaneously in two compartments connected by a pump loop. The conversion of substrate alcohol was 91%, the selectivity toward the product butyrate ester 90%, and the enantiomeric excess of the (S)-product 93% ee.
[反应：见正文]。偶姻（α-羟基酮）是有机合成中的重要结构单元，例如用于埃坡霉素的全合成。光学纯的偶姻可通过用例如洋葱伯克霍尔德菌脂肪酶对外消旋体进行脂肪酶催化的动力学拆分（KR）来获得，但该过程的产率限制为50%。为了设计动态动力学拆分（DKR），我们研究了两种不同偶姻及其相应酯与各种胺碱和离子交换剂的外消旋化。未发现碱和溶剂的组合能在DKR所需的条件下选择性地使偶姻或相应酯外消旋化。与碱不同，发现酸性树脂（ARs）能在正己烷和水中选择性地使偶姻外消旋化。不幸的是，AR使脂肪酶失活，从而无法进行一锅法DKR。还观察到涉及AR、底物偶姻和乙烯基酯酰基供体的轻微副反应。然而，通过脂肪酶和离子交换剂的空间分离实现了高效的DKR，酶促酯交换反应和AR催化的外消旋化在由泵回路连接的两个隔室中同时进行。底物醇的转化率为91%，对产物丁酸酯的选择性为90%，（S）-产物的对映体过量为93%ee。
