ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

不对称合成——结构、立体化学和核磁共振

• 批准号: 3964446
• 负责人: H ZIFFER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3964446
• 关键词: X ray crystallography; acetates; alcohols; chemical synthesis; cis trans isomerization; cyclic compound; diol; high performance liquid chromatography; hydrolysis; ketones; lithium; nuclear magnetic resonance spectroscopy; photochemistry; racemization; stereochemistry; stereoisomer

In developing methodologies to prepare chiral alcohols and to make tentative assignments of their absolute stereochemistry (based on their method of preparation), we have continued to examine the enantioselective hydrolysis of esters. These hydrolyses are catalyzed by enzymes in the mold Rhizopus nigricans, and the configuration of the alcohol formed can be predicted from considerations of the effective sizes of substituents on the carbinol carbon. While data on the absolute stereochemistry of the more rapidly hydrolyzed enantiomer of the ester were consistent with the rule, a quantitative analysis was carried out to determine the relative contributions that electronic, steric and polarizability factors make both to the formation of the enzyme-substrate complex and to the relative rates of hydrolysis of the enantiomers. Data on the optical purities of the alcohols formed and the percent hydrolysis were employed to calculate an "E" value which describes the relative rates of hydrolysis of the two acetate enantiomers. The data show the relative importance of steric, electronic and polarizability factors and demonstrate that it is possible to predict the optical purity of an alcohol formed using standard values of the size, electronegativity and polarizability of substituents. To complement the methodology developed for the preparation of chiral allylic alcohols described, we carried out a preliminary study to demonstrate that the ketal Claisen rearrangement (a rearrangement of vinyl ethers of allylic alcohols), a reaction that had not previously received much attention, can be used for the synthesis of several sesquiterpenes, cuparene, laurene, bazzanene and trichodiene. Each of these natural products contain a quaternary carbon atom. We propose to employ the established chirality of an allylic alcohol to control the absolute stereochemistry of a quaternary carbon atom formed in the rearrangement.

在开发制备手性醇的方法和 其绝对立体化学的暂定分配（基于其 制备方法），我们继续研究对映选择性 酯的水解。 这些水解是由酶催化的， 霉菌黑根霉，并且形成的醇的构型可以是 从考虑取代基上的有效大小预测 甲醇碳 虽然更多的绝对立体化学的数据 酯的快速水解对映体与规则一致， 进行定量分析，以确定相对 电子、空间位阻和极化率因素的贡献， 酶-底物复合物的形成和相对速率 对映体的水解。 光学纯度的数据 形成的醇和水解百分比用于计算 “E”值描述了两种水解的相对速率 乙酸盐对映体。 数据显示了空间位阻的相对重要性， 电子和极化率因素，并证明这是可能的， 为了预测使用以下标准值形成的醇的光学纯度， 取代基的大小、电负性和极化率。 到 补充了为制备手性烯丙基 醇描述，我们进行了初步研究，以证明， 缩酮Claisen重排（烯丙基的乙烯基醚的重排 醇），一个以前没有受到太多关注的反应，可以 可用于合成几种倍半萜烯、倍半萜烯、月桂烯 巴扎烯和顺丁烯二烯。 这些天然产品中的每一种都含有 季碳原子。 我们建议采用已建立的手性 烯丙醇以控制季铵盐的绝对立体化学 重排反应中形成的碳原子。