Preparation and Muscarinic Antagonism of Optically Active p-Fluorohexahydro-sila-diphenidol

点击翻译按钮获取中文摘要

1.Although, a diastereomer of p-Fluorohexahydro-sila-diphenidol (p-F-HHSiD) precursor with optically active menthol did not crystallize, it was found that diastereomer of p-F-HHSiD precursor with (-) -cholesterol crystallized. Recrystallization of the the diastereomer from pentane was carried out several times to gave optically pure diastereomer in 25% yield.2.Reduction of the diastereomer obtained was reduced with lithium aluminum hydride to give an optically active hydrosilane derivative. Then, the derivative was reacted successfully with potassium hydroxide to yield (+) -p-F-HHSiD in a high optical purity.3.Unfortunately, we did not succeed to obtain the antipode ; (-) -p-F-HHSiD,by fractional crystallization method, because it is difficult to use the resolving agent ; (+) -cholesterol, for the antipode. It was found, however, that methyl iodide derivative of (+) -p-F-HHSiD in 70% o.p.was enriched to over 95% o.p.by recrystallization.4.It is necessary to prepare both enantiomers of p-F-HHSiD in high optical purities to investigate muscarinic antagonism. Now, we are concentrating our efforts to improve the optical purity of methyl iodide derivative of (-) -p-F-HHSiD by a recrystallization method.