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: 4689595
• 负责人: H ZIFFER
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & 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/4689595
• 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. These studies were extended to a series of conjugated allylic alcohols where it was found that one chiral alcohol had formed with an unanticipated configuration. The absolute stereochemistry of this compound was rigorously established by an x-ray crystallographic structure determination. In order to identify other alcohols that form with unexptected configurations, we undertook a series of studies of the relation between the sign of the DC curves of the corresponding p-bromobenzoates and the absolute stereochemistry of these molecules. These studies demonstrated that DC measurements can be used for independent assignments of configuration. Compounds in which these assignments and those based on the microbial method differ require further study. While preparing a series of medium-ring 2-bromo-2-cycloalkenyl acetates, we modified the reaction conditions of a silver catalyzed solvolysis reaction from that described in the literature. Our modification altered the geometry about the double bond of the compound formed from that previously reported. It is now possible to prepare either cis- or trans-2-bromocycloalkenes from the same starting material by adjusting the reaction conditions. These cycloalkenes were used to show that three-bond proton-carbon coupling constants, obtained using a recently developed 2D NMR technique could be used to assign the gometry about similarly tri-substituted double bonds. These assignments previously have been very difficult to make.

在开发制备手性醇和制备手性醇的方法方面 它们的绝对立体化学的初步归属(基于它们的 制备方法)我们继续检查对映体选择性 酯的水解性。这些水解物由体内的酶催化 霉菌黑色根霉，所形成的醇的构型可以 从考虑取代基的有效大小预测的 甲醇碳。这些研究被扩展到一系列共轭的 烯丙醇，其中发现一个手性醇与 一种意想不到的配置。它的绝对立体化学 化合物由x射线晶体结构严格确定。 决心。为了识别其他与之形成的醇 未知的配置，我们进行了一系列研究 相应的DC曲线的符号之间的关系 对溴苯甲酸酯及其分子的绝对立体化学。 这些研究表明，直流测量可以用于独立的 配置的分配。其中的化合物中的这些任务和 那些基于微生物方法的方法不同，需要进一步研究。 在制备一系列中环2-溴-2-环烯基乙酸酯时，我们 银催化溶剂分解反应条件的改进 与文献中所描述的不同。我们的修改改变了 关于由先前形成的化合物的双键的几何关系 据报道。现在可以准备顺式或 通过调整原料中的反式-2-溴环烯从相同原料中分离 反应条件。这些环烯烃被用来证明三键 质子-碳耦合常数，使用最近开发的2D 核磁共振技术可以用来确定类似的几何形状 三取代双键。这些任务以前是非常复杂的 很难制作。