Development of Highly Sensitive Analytical Systems to Determine the Absolute Configuration of Chiral Compounds

开发高灵敏度分析系统以确定手性化合物的绝对构型

• 批准号: 03556014
• 负责人: MEGURO Hiroshi
• 金额: $ 8.83万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03556014/
• 关键词: Absolute configuration; Optical purity; Chirality; Fluorescent reagent; (+)-TBMB carboxylic acid; High performance liquid chromatography; chiral derivatization; D, L-sugar; D, L-amino acid; D, L-glycerol; 発ケイ光性試薬; 高速液体クロマトグラフィー; 光学活性化合物; キラルカ

With aims to develop highly sensitive ways to determine the absolute configurations of chiral molecules, new type of chiral derivatizing agents, (+)-TBMB and (+)-TBB carboxylic acids were designed and prepared. The absolute configurations of the former was determined to be (2S) by X-ray analysis of the L-phenylalanie derivative. They were designed to have a CD (circular dichroism) chromophore, isolated Me groups and fluorescent in the bodies which can be effectively used in the CD, NMR and HPLC analyzes to determine the absolute configuration and the optical purity of chiral molecules.Targets for applying these two reagents were directed to three biomolecules, carbohydrates, amino acids and glycerolipids. The analytical conditions were investigated for the derivatization, purification, separations and detections for each. Consequently, simple and highly sensitive methods were established to analyze the D, L-isomers. For sugars and amino acids, NMR and HPLC were effectively employed in the system. For glycerolipids, circular dichroism (CD) based on exciton chirality way was coupled with HPLC system to build a simultaneous system to determine the absolute configuration and the optical purity. This system was employed in the study on the stereochemistries of lipase-catalyzed hydrolysis of glycerides.

为了开发高灵敏度的手性分子绝对构型测定方法，设计并合成了新型手性衍生试剂（+）-TBMB和（+）-TBB羧酸。通过对L-苯丙氨酸衍生物的X-射线衍射分析，确定前者的绝对构型为（2S）。它们被设计成具有CD（圆二色性）发色团、分离的Me基团和荧光体，可以有效地用于CD、NMR和HPLC分析以确定手性分子的绝对构型和光学纯度。研究了每种衍生化、纯化、分离和检测的分析条件。因此，建立了简单、灵敏度高的D，L-异构体分析方法。对于糖和氨基酸，NMR和HPLC在系统中被有效地采用。对于甘油脂，将基于激子手性的圆二色谱（CD）与HPLC系统耦合，建立了同时测定其绝对构型和光学纯度的系统。该体系用于脂肪酶催化甘油酯水解反应的立体化学研究。

项目成果

Yoshihiro Nishida: "Determination of the Absolate Configuration of monosaccharicles Wing (+)or(-)2-tert-butyl-2methyl-1.3-benzodioxole-4-Carloxpylie Acid and Nigh-xeselution ^1H-n.m.r.Spectnoscopy" Carlohyarate Research. 218. 63-73 (1991)

Yoshihiro Nishida：“单糖翼 ( ) 或 (-)2-叔丁基-2甲基-1.3-苯并二氧杂环戊烯-4-Caroxpylie 酸的绝对构型的测定和 Nigh-xeselution ^1H-n.m.r.光谱学” Carlohyarate Research。

Hirotaka Uzawa, Hiroshi Ohrui, Hiroshi Meguro: "Developments of Practical Methods to Determine the Absolute Configurations of Chiral Glycerols" Kagaku & Seibutsu (Japanese). 29. 394-398 (1991)

Hirotaka Uzawa、Hiroshi Ohrui、Hiroshi Meguro：“确定手性甘油绝对构型的实用方法的发展” Kagaku

H.Uzawa et al.: "A Convenient evaluation of the stereo selectivity of lipase-catalyzed hydrolysis of tri-O-acylglycerols" Biochim.Biophys.Acta. 1169. 165-168 (1993)

H.Uzawa 等人：“脂肪酶催化三-O-酰基甘油水解立体选择性的便捷评估”Biochim.Biophys.Acta。

J.H.Kim et al: "A Highly Sensitive HPLC Method for the Determination of the Absolute configuration and the Optical Purity of Di-O Acyl Glycerd" J.Chromatography. (印刷中). (1994)

J.H.Kim 等人：“测定二-O 酰基甘油的绝对构型和光学纯度的高灵敏度 HPLC 方法”J.Chromatography（出版中）。

H.Uzawa et al.: "A Convenient evaluation of the stereoselectivities of lipase-catalyzed hydrolysis of tri-0-acylglycerols on a chiral phase liquid chromatography." Biochimica et Biophysica Acta. 1169. 165-168 (1993)

H.Uzawa 等人：“在手性相液相色谱上方便地评估脂肪酶催化的三-0-酰基甘油水解的立体选择性。”