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Development of method for assignment of absolute configuration based on an induced axial chirality and its application to natural products

基于诱导轴向手性的绝对构型分配方法的开发及其在天然产物中的应用

基本信息

批准号：
15590004
负责人：
HOSOI Shinzo
金额：
$ 2.3万
依托单位：
Kyushu University of Health and Welfare
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In the present study, we developed a novel method for assignment of absolute configuration, which is applicable to compounds having a single functional group, ex. chiral mono-alcohol.Novel CD chromophoric reagent and a new procedure to determine the absolute configuration of chiral mono-alcohols : 3-cyanocarbonyl-3'-methoxycarbonyl-2,2'-binaphthalene, which can be easily introduced to alcohols, was designed as a unique chromophoric reagent. The CD spectra of the derivatives exhibited bisignate CD curves, indicating that chiral information of the alcohol was definitely transmitted to the binaphthyl chromophore and induced axial chirality. According to the analysis of the relationship between exciton chirality and absolute configuration, the alcohols employed were found to be classified into two groups, A and B, which depend strongly upon the structure on the vicinal carbons. Group A constitutes compounds lacking an unsaturation or an oxygen atom on the vicinal carbons, whereas group B c … More onstitutes compounds possessing either an unsaturation or an oxygen atom at the vicinal position. In group A, exciton chirality of (R)-alcohols was negative and that of (S)-alcohols was positive. On the contrary, the signs of exciton chirality were opposite in group B. On the basis of the above results, we proposed a new method to determine the absolute configuration of chiral mono-aicohols.Origin of the induced axial chirality : the transmission of the chirality observed in the derivatives was proved to occur in a thermodynamicaly controlled fashion based on the NMR experiments and molecular mechanics calculations.Development of induced exciton-coupled CD (ECCD) method : it was found that a close relationship between the sign of exciton chirality and the screw sense between the two longitudinal ^1B_b electric transition moments of 2-naphthoate groups in the most stable conformer of the binaphthyl derivative calculated by molecular mechanics : the esters showing positive exciton chirality had a clockwise (C) turn, whereas those with negative exciton chirality show a counterclockwise (CC) turn. Based on the results, a modified procedure for determining absolute configurations using an induced CD method and molecular mechanics calculations was proposed.Application of the method to natural products : the method was applied to yohimbine, an important indole alkaloid in order to prove its usefulness for the assignment of absolute configuration. The absolute configuration has already been determined by a single-crystal X-ray analysis of yohimbine hydrochloride (C17 : S). The CD spectrum of the derivative from yohimbine showed a positive exciton chirality. On the basis of the data from the molecular mechanics calculation of the 17S-derivative, it was found that 17S-isomer preferentially exhibits a clockwise screw sense (C/CC=56/44). The absolute configuration of yohimbine at C17 was thus S. Less

在本研究中，我们开发了一种新的方法来指定绝对构型，这是适用于具有一个单一的功能团，如化合物的化合物。设计了一种新的CD显色剂和一种测定手性一元醇绝对构型的新方法：3-氰基羰基-3 '-甲氧羰基-2，2'-联萘，该试剂易于引入醇中，是一种独特的显色剂。衍生物的圆二色谱均呈现双符号圆二色谱曲线，表明醇的手性信息确实传递给了联萘发色团，并诱导了轴向手性。根据激子手性与绝对构型关系的分析，发现所用的醇可分为A和B两类，它们强烈地依赖于邻位碳的结构。基团A构成在邻位碳上缺少不饱和或氧原子的化合物，而基团B c ...更多信息取代在邻位具有不饱和或氧原子的化合物。A组（R）-醇类为负激子手性，（S）-醇类为正激子手性。相反，B组的激子手性符号相反。在此基础上，我们提出了一种确定手性单羟基化合物绝对构型的新方法.诱导轴向手性的来源：基于NMR实验和分子力学计算，证明了在衍生物中观察到的手性传递是以化学控制的方式发生的.诱导激子耦合CD（ECCD）方法的发展：发现在分子力学计算的联萘衍生物的最稳定构象中，激子手性的符号与2-萘甲酸酯基团的两个纵向^1B_b电跃迁矩之间的螺旋方向有密切的关系：显示正激子手性的酯具有顺时针（C）转向，而具有负激子手性的酯显示逆时针（CC）转向。在此基础上，提出了一种用诱导CD法和分子力学计算确定化合物绝对构型的改进方法，并将其应用于天然产物中，以吲哚类生物碱育亨宾为例，验证了该方法在确定化合物绝对构型中的有效性。用单晶X射线分析法测定了盐酸育亨宾（C_（17）：S）的绝对构型。育亨宾衍生物的圆二色光谱显示正激子手性。根据17 S-衍生物的分子力学计算数据，发现17 S-异构体优先表现出顺时针螺旋方向（C/CC=56/44）。因此育亨宾在C17的绝对构型为S。少