陈绳铨, 耿荣良, 王世椿. γ-氨基丁酸受体激动剂——5-氨甲基-3-羟基异噁唑(muscimol)的简便合成路线J. 药学学报, 1983, 18(11): 865-867.
引用本文: 陈绳铨, 耿荣良, 王世椿. γ-氨基丁酸受体激动剂——5-氨甲基-3-羟基异噁唑(muscimol)的简便合成路线J. 药学学报, 1983, 18(11): 865-867.
CHEN Sheng-quan, GENG Rong-liang, , WANG Shi-chun. A NEW SIMPLIFIED NETHOD FOR THE SYNTHESIS OF MUSCIMOL (5-AMINOMETHYL-3-HYDROXYISOXAZOLE)J. Acta Pharmaceutica Sinica, 1983, 18(11): 865-867.
Citation: CHEN Sheng-quan, GENG Rong-liang, , WANG Shi-chun. A NEW SIMPLIFIED NETHOD FOR THE SYNTHESIS OF MUSCIMOL (5-AMINOMETHYL-3-HYDROXYISOXAZOLE)J. Acta Pharmaceutica Sinica, 1983, 18(11): 865-867.

γ-氨基丁酸受体激动剂——5-氨甲基-3-羟基异噁唑(muscimol)的简便合成路线

A NEW SIMPLIFIED NETHOD FOR THE SYNTHESIS OF MUSCIMOL (5-AMINOMETHYL-3-HYDROXYISOXAZOLE)

  • Abstract: A new and convenient method for the synthesis of muscimol (1) from reaaily available 5-hydroxymethyl-3-hydroxyisoxazole (Ⅱ) was investigated. Without protection of the 3-hydroxy group, Ⅱ was Converted to 5-chloromethyl-3-hydroxy isoxazole (Ⅲ) by direct treatment with thionyl chloride in 75% yield, mp 100~102℃. It was a key step for the production of Ⅰ. The intermediate Ⅲ was aminated to the title compound with agueous ammonia in the presence of ammonium carbonate at 60~70℃ under atmospheric pressure. Thepure product was obtained through fractional crystallization, and the conventional purification step with ion exchange resin was omitted. The melting point of purified compound Ⅰ, 178.9℃ (d), was identical with that synthesized by Gagneux et al(3). Yield of the pure product was 30~40%. It was also identified by IR-, MS-spectroscopy and elemental analysis as well as some biological tests.

     

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