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

光学活性对氟六氢硅二苯酚的制备及其毒蕈碱拮抗作用

• 批准号: 07651026
• 负责人: TERUNUMA Daiyo
• 金额: $ 1.41万
• 依托单位: Saitama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07651026/
• 关键词: p-F-HHSiD; Optical resolution; Muscarinic antagonism; 抗ムスカリン剤; 生理活性有機ケイ素; 光学活性有機ケイ素

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.

1.虽然p-F-HHSiD前体与光学活性薄荷醇的非对映体不结晶，但发现p-F-HHSiD前体与（-）-胆固醇的非对映体结晶。2.用氢化铝锂还原该非对映体，得到光学活性的氢化硅烷衍生物。3.由于（+）-胆固醇对映体的拆分困难，采用分步结晶法未能得到（-）-p-F-HHSiD对映体。然而，发现（+）-p-F-HHSiD的甲基碘衍生物在70% o. p.中富集至超过95%重结晶。4.必须制备高光学纯度的p-F-HHSiD的两种对映体以研究毒蕈碱拮抗作用。o.p.by目前，我们正致力于通过重结晶方法提高（-）-p-F-HHSiD的碘甲烷衍生物的光学纯度。