Mechanism of benzylsuccinate synthase: Stereochemistry of toluene addition to fumarate and maleate
Mechanism of benzylsuccinate synthase: Stereochemistry of toluene addition to fumarate and maleate
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DOI：
10.1021/ja051972f
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发表时间：
2005-06-22
影响因子：
15
通讯作者：
Marsh, ENG
中科院分区：
文献类型：
--
作者：
Qiao, CH;Marsh, ENG
苄基琥珀酸合成酶催化一个非常不寻常的反应：甲苯加成到富马酸形成（R）-苄基琥珀酸。使用[d3-甲基]甲苯和富马酸酯或其顺式立体异构体马来酸酯作为底物，检查了该反应的立体化学。我们证明，当富马酸酯为共底物时，氘从甲苯转移到丁二酸苄酯的C-3 pro-（R）位置，这意味着甲苯对富马酸酯双键的顺式加成。然而，当马来酸酯是共底物时，甲苯的加成以反方式发生，因此也观察到氘转移到苄基琥珀酸酯的C-3 pro-（R）位置。这与丁二酸苄酯作为中间体的C-3基团的形成是一致的，其中当马来酸酯是共底物时，可以发生围绕C-2−C-3键的旋转以减轻羧酸酯基团的空间不利的顺式构象。
Benzylsuccinate synthase catalyzes a highly unusual reaction: the addition of toluene to fumarate to form (R)-benzylsuccinic acid. The stereochemistry of this reaction has been examined using [d3-methyl]toluene and either fumarate or its cis stereoisomer, maleate, as the substrates. We demonstrate that when fumarate is the cosubstrate, deuterium is transferred from toluene to the C-3 pro-(R) position of benzylsuccinate, implying a syn addition of toluene to the double bond of fumarate. However, when maleate is the cosubstrate, the addition of toluene occurs in an anti fashion, so that deuterium transfer to the C-3 pro-(R) position of benzylsuccinate is also observed. This is consistent with the formation of the C-3 radical of benzylsuccinate as an intermediate, in which rotation about the C-2−C-3 bond can occur to relieve the sterically unfavorable cis conformation of the carboxylate groups when maleate is the cosubstrate.