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    • 8. 发明授权
    • Process for producing phosphonomycin
    • 产生膦酰霉素的方法
    • US4222970A
    • 1980-09-16
    • US916145
    • 1978-06-16
    • Roberto Montanari
    • Roberto Montanari
    • C07F9/655C07F9/40
    • C07F9/65505
    • A novel synthesis of the antibiotic phosphonomycin provided which avoids formation of butylphosphochloridite and instead obtains the intermediate butyl-propinyl-phosphite by the mixed anhydrides method. Simplified reaction apparatus is used. Very high yields of a further intermediate, di-t-butylpropadienylphosphate are obtained using the mixed anhydrides process starting with dibutylphosphite. The synthesis of phosphomycin is carried further by hydrogenation of the di-t-butylpropadienylphosphonate using hydrazine hydrate and Ni-Raney with excellent yields to give the second intermediate di-t-butyl-cis-1,2-propenylphosphonate which is in turn converted to the desired phosphomycin by converting to the free phosphonic acid e.g., by reflux with strong acid to remove the t-butoxy groups, followed by epoxidation of the resultant phosphonic acid with hydrogen peroxide and sodium tungstate to yield cis-1,2-epoxypropylphosphonic acid. Optical resolution is then carried out by selective crystallization with (+)-.alpha.-phenylethylamine and recrystallization.
    • 提供了抗生素膦酰霉素的新型合成物,其避免形成丁基磷酸盐,并通过混合酸酐法获得中间体丁基 - 丙基 - 亚磷酸酯。 使用简化的反应装置。 使用起始于亚磷酸二丁酯的混合酸酐方法获得非常高的另外中间体,二叔丁基丙二炔基磷酸酯的产率。 磷霉素的合成通过使用水合肼和Ni-Raney氢化二叔丁基丙二炔基膦酸盐进一步进行,产率高,得到第二中间体二叔丁基 - 顺式-1,2-丙烯基膦酸酯,然后转化为 通过转化成游离膦酸,例如通过用强酸回流除去叔丁氧基,然后用过氧化氢和钨酸钠环氧化得到的膦酸,得到顺式-1,2-环氧丙基膦酸。 然后通过用(+) - α-苯乙胺的选择性结晶进行光学拆分并重结晶。