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New Strategy for Determining the Absolute Stereochemistry of Mono-Functional Natural Products by the CD Exciton Chirality Method

CD激子手性法测定单功能天然产物绝对立体化学的新策略

基本信息

批准号：
11480159
负责人：
HARADA Nobuyuki
金额：
$ 9.47万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480159/
关键词：
Molecular Chirality CD Exciton Chirality Method Absolute Stereochemistry Chiral Auxiliary Enantioresolution X-Ray Crystallography Chiral Recognition by NMR %EE Determination by MS 2-メトキシ-2-(1-ナフチル)プロピオン酸光学純度 MSスペクトルによる鏡像体過剰決定キラルフタル

项目摘要

1. We have developed a new strategy for determining the absolute configuration of mono-fucntional compounds by the CD exciton chirality method. This method is powerful for the absolute configurational studies of chiral compounds including natural products.2. We have recently developed two "powerful chiral acids" for enantioresolution of various alcohols by HPLC on silica gel and also for determination of their absolute configurations by X-ray crystallography and/or by the 1H NMR anisotropy method. The first is the chiral dichlorophthalic acid (-)-1, which was reacted with racemic alcohol to give a diastereomeric mixture of esters. The mixture of esters obtained was separated by HPLC on silica gel, and two separated esters were crystallized respectively to afford single crystals suitable for X-ray analysis. The absolute configuration of the alcohol part was determined by X-ray crystallography of the esters, and enantiopure alcohols were easily recovered by solvolysis with K_2CO_3 in methanol.3. The second powerful chiral acid is 2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid, (S)-(+)-2 or R-(-)-2) for determining the absolute configuration of chiral alcohols by the 1H NMR anisotropy method.The enantiopure MαNP acid (S)-(+)-2 was allowed to react with racemic alcohols yielding diastereomeric mixtures of esters, which were easily separated by HPLC on silica gel. The NMR signals of diastereomeric esters obtained were fully assigned by the various two-dimensional methods leading to the calculation of Δδ values (Δδ = δ(R,X)-δ(S,X)). By applying the MαNP sector rule, the absolute configuration X was determined. Separated esters were hydrolyzed with KOH/EtOH to recover enantiopure alcohols.4. Using MαNP acid, (S)-(+)-2 and its deuterium labeled enantiomer R-(-)-2-d_6, we have developed a new diastereomer method for determining enantiomeric excess (% ee) of chiral alcohols by MS spectrometry.

1.本文发展了一种用CD激子手性方法确定单功能化合物绝对构型的新方法。该方法对于手性化合物包括天然产物的绝对构型研究具有重要意义.我们最近开发了两种“强大的手性酸”，通过HPLC在硅胶上对各种醇进行对映体拆分，并通过X射线晶体学和/或1H NMR各向异性方法确定其绝对构型。第一种是手性二氯邻苯二甲酸（-）-1，其与外消旋醇反应得到酯的非对映体混合物。所得酯的混合物通过HPLC在硅胶上分离，并且两种分离的酯分别结晶以提供适合于X射线分析的单晶。醇部分的绝对构型由酯的X-射线晶体学确定，并且对映纯醇易于用K_2CO_3在甲醇中溶剂解回收。第二个强手性酸是2-甲氧基-2-（1-萘基）丙酸（MαNP酸，（S）-（+）-2或R-（-）-2），它与外消旋醇反应生成酯的非对映异构体混合物，在硅胶上很容易用HPLC分离。通过各种二维方法对所得非对映体酯的NMR信号进行了完全归属，从而计算出Δδ值（Δδ = δ（R，X）-δ（S，X））。应用MαNP扇形规则，确定了X的绝对构型.分离的酯用KOH/EtOH水解以回收对映体纯醇。利用MαNP酸（S）-（+）-2及其氘标记的对映体R-（-）-2-d_6，建立了一种新的非对映体质谱法测定手性醇对映体过量（% ee）。