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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10555272/
• 关键词: Optical resolution; Preferential crystallization; Racemic compound (Racemate); Racemic mixture (Conglomerate); Isomerization reaction; 光学異性体; スレオニン; BOC-ピペラジン; DOPA

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.

在医药和食品工业中，需要建立获得高纯度和高产率的光学异构体的操作。这是因为生物利用度以及对映体特有的味道强烈依赖于产品的光学纯度。本研究的目的是通过实验研究优先结晶应用于形成外消旋混合物的体系的可能性，因为大多数光学活性体系形成外消旋化合物，在进行这些实验工作之前，进行了实验研究，以寻找优先结晶过程的机理，在DL-ThreeGlass形成系统的优先结晶后期，纯度下降。通过分析不需要的异构体（D-Thr）的沉积行为，得出了D-Thr在L-Thr晶体表面形成的机理。然后用BOC-哌嗪的外消旋化合物，实验检查了优先结晶的可能性，并通过外消旋体和对映体之间的结晶速率（成核和生长）不同的事实来证实。最后，对DL-多巴体系的异构化反应与优先结晶相结合的原理进行了探讨，测定了异构化反应动力学和结晶速率，表明在溶剂脱除速率与动力学相等的条件下，稳定连续操作是可能的。

项目成果

V.M.Profir and M.Matsuoka: "Processes and Phenomena of Purity Decrease during the Optical Resolution of DL-Threonine by Preferential Crystallization"Colloids and Surfaces, A : Physicochemical and Engineering Aspects. Vol.164. 315-324 (2000)

V.M.Profir 和 M.Matsuoka：“通过优先结晶光学拆分 DL-苏氨酸过程中纯度降低的过程和现象”胶体和表面，A：物理化学和工程方面。

V.M.Profir and M.Matsuoka: "Processes and Phenomena of Purity Decrease during the Optical Resolution of DL-Threonine by Preferential Crystallization"Colloids and Surfaces, A : Physicochemical and Engineering Aspects. 164. 315-324 (2000)

V.M.Profir 和 M.Matsuoka：“通过优先结晶光学拆分 DL-苏氨酸过程中纯度降低的过程和现象”胶体和表面，A：物理化学和工程方面。

V.M.Profir and M.Matsuoka: "Processes and Phenomena of Purity Decrease during the Optical Resolution of DL-Threonine by Preferential Crystallization"Colloids and Surfaces. 164. 315-324 (2000)

V.M.Profir 和 M.Matsuoka：“通过优先结晶光学拆分 DL-苏氨酸过程中纯度降低的过程和现象”胶体和表面。