权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on generalization of a new enantiomeric resolution phenomenon (Preferential Enrichment)

新的对映体拆分现象的推广研究（优先富集）

基本信息

批准号：
10440187
负责人：
TAMURA Rui
金额：
$ 4.86万
依托单位：
KYOTO UNIVERSITY
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 2001
项目状态：
已结题

项目摘要

In order to elucidate the mechanism of Preferential Enrichment, the following four points must be fully understood; (i) the supramolecular association structure in solution, (ii) the crystal structure of the metastable crystalline phase formed kinetically from the supersaturated solution, (iii) the mechanism of polymorphic transition of the metastable crystalline phase into the stable form in the supersaturated solution. For the understanding of (i), the solubility and supersolubility measurement of the solid material, the number-averaged molecular weight measurement in solution, and the molecular dynamics simulation of the stable supramolecular association structure were carried out. For the isolation of the metastable crystals in (ii), the epitaxial crystallization by using seed crystals, or the selective crystallization of the desired polymorph by inhibition of the nucleation or crystal growth process of an undesired stable polymorph were used. In addition, when the single crystal f … More or X-ray crystallographic analysis was not available, the crystal structure was able to be solved from the powder X-ray diffraction data by the Monte Carlo method and the subsequent Rietveld refinement. For the aim of (iii), the in situ and real time AIR-IR measurement of the supersaturated solution or the DSC measurement of the deposited crystals was effective. It was also shown that the mechanism of polymorphic transition could be rationalized by comparison of the metastable and stable crystal structures. By using these methods, the following four results concerning the mechanism of Preferential Enrichment were obtained.(1) In a solution of the racemate showing Preferential Enrichment, the homochiral molecular association is preferred to the heterochial one.(2) The nature of the racemic crystal of the compound showing Preferential Enrichment has been classified as a fairly ordered racemic mixed crystal composed of the two enantiomers.(3) The mechanism of Preferential Enrichment is closely associated with the polymorphic transition occurring during crystallization from the supersaturated solution.(4) By comparison of the crystal structures before and after the phase transition, the mechanism of the solid-to-solid type of polymorphic transition can be understood. On the basis of this mechanism, the unique mechanism of Preferential Enrichment has been proposed. Less

为了阐明优先富集的机理，必须充分理解以下四点：（i）溶液中的超分子缔合结构，（ii）从过饱和溶液动力学形成的亚稳结晶相的晶体结构，（iii）在过饱和溶液中亚稳结晶相向稳定形式的多晶型转变的机理。为了理解（i），进行了固体材料的溶解度和超溶解度测量、溶液中的数均分子量测量以及稳定的超分子缔合结构的分子动力学模拟。为了分离（ii）中的亚稳晶体，使用通过使用晶种的外延结晶，或通过抑制不希望的稳定多晶型物的成核或晶体生长过程的所需多晶型物的选择性结晶。此外，当单晶f ...更多信息或X射线晶体学分析不可用时，晶体结构能够通过Monte Carlo方法和随后的Rietveld精修从粉末X射线衍射数据解出。对于（iii）的目的，过饱和溶液的原位和真实的时间AIR-IR测量或沉积晶体的DSC测量是有效的。通过对亚稳态和稳态晶体结构的比较，可以合理地解释多晶型转变的机理。利用这些方法，得到了以下四个有关优先富集机理的结果。(1)在外消旋体的溶液中，表现出优先富集，同手性分子缔合优于异手性分子缔合。(2)显示优先富集的化合物的外消旋晶体的性质已被分类为由两种对映异构体组成的相当有序的外消旋混合晶体。(3)优先富集的机理与过饱和溶液结晶过程中的多晶型转变密切相关。(4)通过对相变前后晶体结构的比较，可以理解固-固型多晶型转变的机理。在此基础上，提出了独特的优先富集机制。少