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

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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