STUDIES IN THE SHIKIMATE-CHORISMATE PATHWAY

一个基础广泛的生物有机程序，用于研究一些关键酶 在莽草酸-分支酸途径中被概述。关键要素是 以下是： 1.氯酸变位酶：新的过渡态类似物抑制剂将是 合成和评估；合成分支酸本身将是 完成。 2.3-脱氢奎尼酸合成酶：各个步骤的立体化学 在酶促转化过程中将由立体选择性决定 关键中间体的合成；封闭底物和过渡反应 将合成和评价状态类似物抑制剂。 3.氯酸合成酶：天然底物的烯丙基异构体 作为替代底物或缓蚀剂进行合成和评价。 4.5-烯丙酮基莽草酸-3-磷酸合成酶：假设的四面体 将合成加合物并将其酶转化为产物 评估；过渡态和多底物类似物抑制剂也将 是人工合成的。 5.预苯酸脱水酶：一系列亚砜和磺胺类似物 将合成预苯酯并作为过渡态类似物进行评估 或者是自杀抑制药。 6.莽草酸-分支酸中间体的一些其他类似物 途径被认为是底物和抑制剂。

A broadly based bioorganic program for the study of some of the key enzymes in the shikimate-chorismate pathway is outlined. The key elements are the following: 1. Chorismate mutase: New transition state analog inhibitors will be synthesized and evaluated; a synthesis of chorismic acid itself will be completed. 2. 3-Dehydroquinate synthase: The stereochemistry of the individual steps in the enzymic transformation will be determined by stereoselective synthesis of a key intermediate; blocked-substrate as well as transition state analog inhibitors will be synthesized and evaluated. 3. Chorismate synthetase: An allylic isomer of the natural substrate will be synthesized and evaluated as an alternative substrate or inhibitor. 4. 5-Enolpyruvylshikimate-3-phosphate synthase: The postulated tetrahedral adduct will be synthesized and its enzymatic conversion to product evaluated; transition state and multisubstrate analog inhibitors will also be synthesized. 5. Prephenate dehydratase: A series of sulfoxide and sulfilimine analogs of prephenate will be synthesized and evaluated as transition state analog or suicide inhibitors. 6. A number of other analogs of intermediates in the shikimate-chorismate pathway are proposed as substrates and inhibitors.