Active Site Model of Lipases and Control of Stereoselectivity of Lipase-catalyzed Transesterifications

脂肪酶催化的酯交换反应的立体选择性酶在有机合成中作为手性催化剂越来越受欢迎，而脂肪酶因其价格相对低廉，可以在有机和水溶液中发挥作用，使用简单，对多种底物表现出高的对映选择性而特别吸引人。现在我们用廉价易得的脂肪酶QL研究了有机溶剂中外消旋醇的立体化学对映体选择性酯交换反应。根据观察到的对映体选择性，我们提出了产碱杆菌脂肪酶QL的活性中心模型，作为经验法则来确定在活性中心可以容纳的伯醇和仲醇以及它们在酰化反应中反应较快的对映体。光学活性冠醚的合成及其在与手性胺的络合中的对映体选择性的合成光学活性冠醚与手性胺的络合对映体选择性的了解是研究酶-底物络合物形成手性识别的重要信息。我们现在发现，冠醚与胺的络合反应中对映体选择性随温度的变化而逆转，在等对映体选择性温度以上，对映体选择性随着温度的升高而增加。人们普遍认为，在手性反应中，较低的温度可以提高对映体的选择性，但我们的结果表明，这一观点并不总是正确的。

Stereoselectivity of lipase-catalyzed transesterificationsEnzymes have become increasingly popular as chiral catalysts in organic synthesis and lipases are especially attractive for this purpose because they are relatively inexpensive can function in both organic and aqueous solutions, are simple to use and show high enantioselectivity for a broad range of substrates. We now examined stereochemistry of enantioselective transesterification of racemic alcohols in organic solvents by using lipase QL which is readily available and inexpensive. On the basis of the observed enantioselectivities, we proposed the active site model for lipase QL from Alcaligenes sp.as a rule of thumb to identify the primary and secondary alcohols which can be accommodated in the active site and their faster-reacting enantiomer in this acylation.Synthesis of optically active crown ethers and their enantiomer selectivities in the complexation with chiral aminesThe knowledge of the enantiomer selectivity in the complexation of optically active crown ethers with chiral amines serves as an important information for studing the chiral recognition in the formation of an enzyme-substrate complex.We now found the temperature dependent reversal of the enantiomer selectivity in the complexation of crown ethers with the amine and the enantiomer selectivities increased with increasing temperature above the isoenantioselective temperature. It is the generally accepted view that lower temperatures enhance the enantiomer selectivity in chiral processes but our results suggests that the view is not always correct.