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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. 我们开发了一种通过圆二色激子手性方法测定单功能化合物绝对构型的新策略。该方法对于包括天然产物在内的手性化合物的绝对构型研究具有强大的作用。 2．我们最近开发了两种“强手性酸”，用于通过硅胶上的 HPLC 对各种醇进行对映拆分，并通过 X 射线晶体学和/或 1 H NMR 各向异性方法测定其绝对构型。第一种是手性二氯邻苯二甲酸(-)-1，它与外消旋醇反应得到酯的非对映混合物。将获得的酯混合物通过硅胶HPLC分离，并将分离的两种酯分别结晶，得到适合X射线分析的单晶。通过酯的X射线晶体学测定了醇部分的绝对构型，并且通过K_2CO_3在甲醇中的溶剂解很容易回收对映体纯醇。 3．第二种强手性酸是 2-甲氧基-2-(1-萘基)丙酸（MαNP 酸，(S)-(+)-2 或 R-(-)-2），用于通过 1H NMR 各向异性方法测定手性醇的绝对构型。对映体纯 MαNP 酸 (S)-(+)-2 与外消旋醇反应，产生非对映异构体酯的混合物，可以通过硅胶上的 HPLC 轻松分离。获得的非对映酯的 NMR 信号通过各种二维方法完全分配，从而计算 Δδ 值 (Δδ = δ(R,X)-δ(S,X))。通过应用MαNP扇区规则，确定了绝对构型X。分离的酯用KOH/EtOH水解回收对映体纯醇。4．利用 MαNP 酸 (S)-(+)-2 及其氘标记的对映体 R-(-)-2-d_6，我们开发了一种新的非对映体方法，通过质谱法测定手性醇的对映体过量 (% ee)。