Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons
Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons
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DOI：
10.1038/nprot.2007.354
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发表时间：
2007-01-01
期刊：
影响因子：
14.8
通讯作者：
Shao, Feng
中科院分区：
文献类型：
--
作者：
Hoye, Thomas R.;Jeffrey, Christopher S.;Shao, Feng
该方案详细介绍了最常用的基于核磁共振（NMR）的方法，用于推导另外未知的立体异构仲甲醇（醇）中心（（RRCHOH）-R-1-C-2（或其中OH被NH 2取代的类似胺））的构型。这种“Mosher酯分析”依赖于非对映异构体α-甲氧基-α-三氟甲基苯乙酸（MTPA）酯（即，那些衍生自甲醇在与MTPA的询问下的共轭的化合物）在它们的H-1 NMR谱中显示出不同的化学位移（δ s）排列。该方案包括以下内容：（i）制备每种非对映体S-和R-MTPA酯，以及（ii）对这两种酯的H-1 NMR光谱数据进行比较（DdSR）分析。通过分析非对映体酯（或酰胺）中许多类似质子对的化学位移差异的符号（DdSR值集），可以可靠地推导出原始甲醇（或氨基）立构中心的绝对构型。典型的Mosher酯分析需要在1至2天的时间内进行约4-6小时的主动工作。
This protocol details the most commonly used nuclear magnetic resonance (NMR)-based method for deducing the configuration of otherwise unknown stereogenic, secondary carbinol (alcohol) centers ((RRCHOH)-R-1-C-2 (or the analogous amines where OH is replaced by NH2)). This 'Mosher ester analysis' relies on the fact that the protons in diastereomeric alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA) esters (i.e., those derived from conjugation of the carbinol under interrogation with MTPA) display different arrays of chemical shifts (delta s) in their H-1 NMR spectra. The protocol consists of the following: (i) preparation of each of the diastereomeric S- and R-MTPA esters and (ii) comparative (DdSR) analysis of the H-1 NMR spectral data of these two esters. By analyzing the sign of the difference in chemical shifts for a number of analogous pairs of protons (the set of DdSR values) in the diastereomeric esters (or amides), the absolute configuration of the original carbinol (or amino) stereocenter can be reliably deduced. A typical Mosher ester analysis requires approximately 4-6 h of active effort over a 1- to 2-d period.