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。我们已经开发了一种新的策略来确定CD Interned手性方法对单核化合物的绝对构型。此方法对于包括天然产品在内的手性化合物的绝对构型研究非常有力。2。我们最近开发了两个“强大的手性酸”，用于通过HPLC在硅胶上对各种醇的映线，也通过X射线晶体学和/或1H NMR各向异性方法来确定其绝对构型。第一个是手性二氯健康（ - ）-1，它与乙醇酒精反应以产生酯的非映异构体混合物。通过在硅胶上通过HPLC分离所获得的酯的混合物，分别将两个单独的酯结晶，以提供适合X射线分析的单晶。酒精部分的绝对构型由酯的X射线晶体学确定，并通过甲醇中的K_2CO_3溶剂化很容易回收映体醇。3。第二强手性酸是2-甲氧基-2-（1-萘基）丙酸（MαNP酸，（s） - （+） - 2或r-（ - （ - ） - 2），用于确定1H NMR偏射方法对手性酒精的绝对构型。酯，在硅胶上很容易通过HPLC分离。通过各种二维方法完全分配了对非对非洲裔酯的NMR信号，从而导致计算Δδ值（Δδ=δ（r，x）-Δ（s，x））。通过应用MαP部门规则，确定了绝对配置X。将分离的酯用KOH/ETOH水解以恢复对映体醇。4。使用MαNP酸，（s） - （+） - 2及其标记为对映异构体R - （ - ） - 2-D_6的氘，我们开发了一种新的非对映异构体方法，用于通过MS光谱法确定手性醇的对映体超过（％EE）。