Patel Hetalben, Shim Da Jeong, Farinas Edgardo T, Jordan Frank
Department of Chemistry, Rutgers University, Newark, NJ 07102.
J Mol Catal B Enzym. 2013 Dec 30;98. doi: 10.1016/j.molcatb.2013.09.010.
The potential of thiamin diphosphate (ThDP)-dependent enzymes to catalyze C-C bond forming (carboligase) reactions with high enantiomeric excess has been recognized for many years. Here we report the application of the E1 component of the 2-oxoglutarate dehydrogenase multienzyme complex in the synthesis of chiral compounds with multiple functional groups in good yield and high enantiomeric excess, by varying both the donor substrate (different 2-oxo acids) and the acceptor substrate (glyoxylate, ethyl glyoxylate and methyl glyoxal). Major findings include the demonstration that the enzyme can accept 2-oxovalerate and 2-oxoisovalerate in addition to its natural substrate 2-oxoglutarate, and that the tested acceptors are also acceptable in the carboligation reaction, thereby very much expanding the repertory of the enzyme in chiral synthesis.
多年来，人们已经认识到硫胺素二磷酸（ThDP）依赖性酶具有催化形成对映体过量值高的碳 - 碳键（碳连接酶）反应的潜力。在此，我们报道了通过改变供体底物（不同的2-氧代酸）和受体底物（乙醛酸、乙醛酸乙酯和甲基乙二醛），将2-氧代戊二酸脱氢酶多酶复合物的E1组分应用于合成具有多个官能团的手性化合物，产率良好且对映体过量值高。主要发现包括证明该酶除了能接受其天然底物2-氧代戊二酸外，还能接受2-氧代戊酸和2-氧代异戊酸，并且所测试的受体在碳连接反应中也是可接受的，从而极大地扩展了该酶在手性合成中的应用范围。
