Development of High-purity Optical Resolution Operations with Simultaneous Isomerization and Preferential Crystallization

同时异构化和优先结晶的高纯度光学拆分操作的发展

基本信息

批准号：
10555272
负责人：
MATSUOKA Masakuni
金额：
$ 8.45万
依托单位：
Tokyo University of Agriculture and Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Establishment of operations of obtaining optical isomers with high purity and high yield is required in the medical and food industries. This is because bio-availability as well as tastes specific to enantiomers are strongly dependent on product optical purity. The present study aims to examine experimentally the possibility of application of preferential crystallization to systems forming racemic mixtures, since most of optically active systems form racemic compounds, and to confirm the validity of the principle of preferential crystallization processes which are combined with isomerization reaction to improve the product yield.Before conducting these experimental works experimental study was carried out to find the mechanism of purity drop in the later stage of preferential crystallization of conglomerate forming systems using DL-Threonine. Analyzing the behavior of deposition of the undesired isomer (D-Thr) leads to the mechanism of the formation of D-Thr on L-Thr crystal surfaces. Then with the racemic compound of BOC-Piperazine, the possibility of preferential crystallization was examine experimentally and was confirmed by the fact that the rates of crystallization (nucleation and growth) were different between the racemate and the enantiomer. Finally the principle of preferential crystallization with the combination of isomerization reaction was examined for the system of DL-DOPA.The kinetics of isomerization reaction together with crystallization rates were determined, and it was shown that under the conditions that the rate of removal of solvents from the system are set equal to those kinetics stable continuous operations are possible.

在医疗和食品行业需要建立高纯度和高收益的光学异构体的操作。这是因为生物可用性以及特定于对映异构体的品味在很大程度上取决于产品光学纯度。 The present study aims to examine experimentally the possibility of application of preferential crystallization to systems forming racemic mixtures, since most of optically active systems form racemic compounds, and to confirm the validity of the principle of preferential crystallization processes which are combined with isomerization reaction to improve the product yield.Before conducting these experimental works experimental study was carried out to find the mechanism of purity drop in the later stage of preferential crystallization of conglomerate使用DL-硫代氨酸成立系统。分析不希望的异构体（D-THR）沉积的行为导致L-THR晶体表面D-THR形成的机理。然后，使用BOC二哌嗪的外消旋化合物，通过实验检查了优先结晶的可能性，并通过结晶速率（成核和生长）在种族主义和对映体之间有所不同。最后，研究了与异构化反应的组合的优先结晶原理，以确定异构化反应系统。同构化反应的动力学与结晶速率一起确定，并且证明在从系统中取出溶剂的去除率等于这些动力学稳定的持续操作相等。