An, Ming ; Maitra, Uday ; Neidlein, Ulf ; Bartlett, Paul A. (2003) 5-Enolpyruvylshikimate 3-phosphate synthase: chemical synthesis of the tetrahedral intermediate and assignment of the stereochemical course of the enzymatic reaction Journal of the American Chemical Society, 125 (42). pp. 12759-12767. ISSN 0002-7863
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Official URL: http://pubs.acs.org/doi/abs/10.1021/ja036627%2B
Related URL: http://dx.doi.org/10.1021/ja036627+
Abstract
A chemical synthesis of both diastereomers of the tetrahedral intermediate involved in 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) catalysis has been accomplished. Combination of methyl dibromopyruvate with a protected shikimic acid derivative, phosphorylation, and lactonization afforded the intermediates (S)-15 and (R)-15, whose configurations were assigned by NMR. After introduction of the 3-phosphate group and deprotection, photoinitiated radical debromination of the dibromo analogues (S)-5 and (R)-5 was accomplished with tributyltin hydride in mixed aqueous solvents in the presence of surfactant to give the pyruvate ketal phosphates (R)-TI and (S)-TI, respectively. These compounds are stable at high pH, but decompose at pH 7 with a half-life of ca. 10 min. (R)-TI proved to be inert to EPSPS, while (S)-TI was converted by the enzyme to a mixture of 5-enolpyruvylshikimate 3-phosphate, shikimate 3-phosphate, and phosphoenolpyruvate. The demonstration that the enzymatic intermediate possesses the S-configuration at the ketal center confirms the mechanism as an anti addition followed by a syn elimination. Furthermore, it appears that the syn stereochemistry of the second step requires the phosphate leaving group to serve as the base in catalyzing its own elimination.
Item Type: | Article |
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Source: | Copyright of this article belongs to American Chemical Society. |
ID Code: | 21173 |
Deposited On: | 20 Nov 2010 08:58 |
Last Modified: | 26 Feb 2011 09:22 |
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