UNDERSTANDING ENZYME-CATALYZED PROTON ABSTRACTION FROM CARBON ACIDS - DETAILS OF STEPWISE MECHANISMS FOR BETA-ELIMINATION REACTIONS
UNDERSTANDING ENZYME-CATALYZED PROTON ABSTRACTION FROM CARBON ACIDS - DETAILS OF STEPWISE MECHANISMS FOR BETA-ELIMINATION REACTIONS
复制标题
DOI：
10.1021/ja00041a004
复制
发表时间：
1992-07-15
影响因子：
15
通讯作者：
GASSMAN, PG
中科院分区：
文献类型：
--
作者：
GERLT, JA;GASSMAN, PG
所观察到的酶催化的从与羰基/羧酸基团相邻的碳（碳酸的α-质子）提取质子的速率要求α-质子的pK（α） 使其等于（+/-2-3 pK（α）单位）或小于质子化活性中心碱性催化剂的pK（α）单位。这可以通过协调的通用酸-通用碱催化来实现：Gerlt，J.A.; Kozarich，J. W.;凯尼恩湾L.的; Gassman，P. G. J. Am. Chem.Soc.1991，113，9667。使用该原理分析各种酶催化的β-消除反应，预测这些反应可能通过逐步机制进行，该机制涉及初始协调的一般酸-一般碱催化形成烯醇中间体，然后消除β-取代基。第二步是乙烯基醚E2反应（1，4-消除）。因此，这些酶并不像人们经常提出的那样催化“简单”的E1 cb反应。在降低碳酸的pK（a）s中，协调的一般酸-一般碱催化的参与可以提供对某些酶催化的β-消除反应的观察到的立体化学过程的洞察。
The observed rates of enzyme-catalyzed abstraction of a proton from a carbon adjacent to a carbonyl/carboxylic acid group (alpha-proton of a carbon acid) require that the pK(a) of the alpha-proton be decreased such that it is equal to (+/-2-3 pK(a) units) or less than that of the protonated active site basic catalyst. This can be accomplished by concerted general acid-general base catalysis: Gerlt, J. A.; Kozarich, J. W.; Kenyon, G. L.; Gassman, P. G. J. Am. Chem. Soc. 1991, 113, 9667. Analysis of various enzyme-catalyzed beta-elimination reactions using this principle leads to the prediction that these reactions are likely to proceed via stepwise mechanisms which involve initial concerted general acid-general base catalyzed formation of an enol intermediate followed by elimination of the beta-substituent. The second step is a vinylogous E2 reaction (1,4-elimination). Thus, these enzymes are not expected to catalyze "simple" E1cb reactions as has often been proposed. The involvement of concerted general acid-general base catalysis in reducing the pK(a)s of carbon acids may provide insight into the observed stereochemical courses of certain enzyme-catalyzed beta-elimination reactions.