STUDIES IN THE SHIKIMATE-CHORISMATE PATHWAY

一个基础广泛的生物有机计划，用于研究一些关键酶 在shikimate-chorismate途径概述。 关键要素是 以下内容： 1. Chorismate ®：新的过渡态类似物抑制剂将成为 合成和评估;将合成氯酸本身， 完成 2. 3-脱氢奎尼酸合酶：各个步骤的立体化学 将通过立体选择性 关键中间体的合成;阻断底物以及过渡 将合成并评价所述类似物抑制剂。 3.分支酸合成酶：天然底物的烯丙基异构体， 合成并作为替代底物或抑制剂进行评价。 4. 5-烯醇式莽草酸-3-磷酸合酶：假定的四面体 将合成加合物并将其酶促转化为产物 评估;过渡态和多底物类似物抑制剂也将 合成。 5.预苯酸酯酶：一系列亚砜和硫亚胺类似物 的预苯酯将被合成并作为过渡态类似物进行评价 或自杀抑制剂。 6.志喜酸-分支酸酯中间体的许多其他类似物 途径被提出作为底物和抑制剂。

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.