GENERATION AND STABILITY OF A SIMPLE THIOL ESTER ENOLATE IN AQUEOUS-SOLUTION
GENERATION AND STABILITY OF A SIMPLE THIOL ESTER ENOLATE IN AQUEOUS-SOLUTION
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DOI：
10.1021/ja00052a028
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发表时间：
1992-12-16
影响因子：
15
通讯作者：
RICHARD, JP
中科院分区：
文献类型：
--
作者：
AMYES, TL;RICHARD, JP
硫代乙酸乙酯和丙酮的α-质子在D2O中的3-奎宁环酮缓冲液中在25℃和pD = 7.7-9.3下与氘进行交换，然后通过H-1 NMR光谱进行跟踪。交换反应导致由于 α-CH2D 和 α-CHD2 物质而产生的信号的出现，这些信号彼此之间以及由于 α-CH3 物质而产生的信号被清楚地分离。观察到的3-奎宁环酮催化交换的速率常数是在硫代乙酸乙酯或丙酮的每个甲基的第一个α-质子的30-37%的交换过程中测定的。交换的速率常数对应于硫代乙酸乙酯和丙酮通过 3-奎宁环酮去质子化得到游离烯醇化物的速率常数，分别为 k(B) = 2.2 X 10(-5) 和 5.2 x 10(-4) M-1 s-1。这些速率常数与已知的丙酮 pK(a) 相结合，估计硫代乙酸乙酯的 pK(a) = 20.4-21.5，游离硫醇酯烯醇化物与 3-奎宁环酮阳离子反应的 k(BH) = 1.7 x 10(8) 至 2 x 10(9) M-1 s-1。缓冲酸-烯醇化物亲密离子对 BH+.-CH2COSEt 相对于质子转移以产生 B.CH3COSEt 的寿命估计为 10(-9) 至 10(-10) s。这些结果提供了反驳以下观点的证据：酶催化的克莱森缩合和相关反应通过协同机制进行，该机制是由在酶上存在酸性氨基酸残基的情况下硫羟酸酯烯醇化物的微不足道的寿命强制执行的。
The exchange for deuterium of the alpha-protons of ethyl thioacetate and of acetone in 3-quinuclidinone buffers in D2O at 25-degrees-C and pD = 7.7-9.3 was followed by H-1 NMR spectroscopy. The exchange reactions lead to the appearance of signals due to the alpha-CH2D and alpha-CHD2 species that are cleanly resolved from each,other and from the signal due to the alpha-CH3 species. Observed rate constants for the 3-quinuclidinone-catalyzed exchange were determined during exchange of 30-37% of the first alpha-proton of each methyl group of ethyl thioacetate or acetone. The rate constants for exchange correspond to those for deprotonation of ethyl thioacetate and acetone by 3-quinuclidinone to give the free enolates, with k(B) = 2.2 X 10(-5) and 5.2 x 10(-4) M-1 s-1, respectively. These rate constants were combined with the known pK(a) of acetone to estimate pK(a) = 20.4-21.5 for ethyl thioacetate and k(BH) = 1.7 x 10(8) to 2 x 10(9) M-1 s-1 for the reaction of the free thiol ester enolate with the 3-quinuclidinone cation. The lifetime of the buffer acid-enolate intimate ion pair BH+.-CH2COSEt with respect to proton transfer to give B.CH3COSEt is estimated to be from 10(-9) to 10(-10) s. These results provide evidence against the suggestion that enzyme-catalyzed Claisen condensation and related reactions proceed by concerted mechanisms that are enforced by the insignificant lifetime of the thiol ester enolate in the presence of an acidic amino acid residue at the enzyme.