SUGAR AND AMINO ACID SYNTHESIS WITH SPECIFIC LABELING

具有特定标记的糖和氨基酸合成

• 批准号: 3283844
• 负责人: DONALD S MATTESON
• 金额: $ 11.24万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283844
• 关键词: aminoacid; boronic acids; carbohydrates; carbon; drug design /synthesis /production; esters; glyceraldehyde; hexoses; lithium; methylene chloride; pentoses; radiotracer; stereochemistry; succinates

A new approach to the controlled chiral synthesis isotopically labeled sugars and amino acids is proposed, based on the efficient homologation of chiral boronic esters with lithiated dichloromethane to form Alpha-chloro boronic esters with very high diastereoselection at the Alpha-carbon. Preliminary work has shown that this homologation works in the presence of Alpha- and Beta-alkoxy groups, and it thus appears that the process can be repeated to introduce as many adjacent oxygen-substituted chiral centers as desired. Both enantiomers of the useful chiral directing groups, pinanediol and 2,3-butanediol, are available, giving the chemist independent absolute control of the configuration at each chiral center. Because of the extremely high stereoselectivity and the fact that all of the carbon is derived from dichloromethane, this process appears particularly promising as a route to regiospecifically and stereospecifically labeled sugars. The synthesis of several common hexoses and pentoses is proposed. Preparations of glyceraldehyde having both a 13C and a stereospecific 2H label at C-3 and also of 1-3H-4-14C-ribulose-5-phosphate are outlined. The method also appears highly promising for preparing amino acids with specifically placed chiral labels, and for chirally labeled methyl groups. The ultimate aim of the work is to provide a simple means of obtaining any desired sugar, amino acid, or related structure with any isotopic labels in any set of specific positions that the biochemist wants in order to answer questions about mechanisms of enzyme reactions and metabolic pathways, which will provide basic biochemical information relevant to a wide variety of health problems.

一种受控手性合成的新方法，以同位素标记 提出了糖和氨基酸，根据 手性硼齿酯含有纤维化的二氯甲烷，形成α-氯 在α-碳处具有非常高的非对映选择的硼烯酯。 初步工作表明，这种处理在存在的情况下起作用 α-和β-烷氧基群，因此似乎可以是 重复引入尽可能多的相邻氧取代的手性中心 需要。 有用的手性指导组的两个对映异构体， Pinanediol和2,3-丁二醇可用，提供化学家 在每个手性中心的构型的独立绝对控制。 由于立体选择性极高，事实是 碳来自二氯甲烷，出现了 特别有前途，作为通往重点的途径，以及 立体特定标记的糖。 几种常见的己糖的合成 并提出了五齿。 具有13c的甘油醛的制剂 以及C-3的立体特定2H标签，也是 概述了1-3H-4-14C-核糖-5-磷酸。 该方法也出现 用特定放置手性制备氨基酸的高度希望 标签，用于手性标记的甲基。 最终目标 工作是提供一种简单的方法来获得任何所需的糖氨基 任何同位素标签的酸或相关结构 生物化学家想要回答有关的问题 酶反应和代谢途径的机制，这将提供 基本的生化信息与各种健康问题有关。