一种克拉霉素关键中间体的合成工艺优化

目的研究克拉霉素关键中间体——（2＇4,″-O-双三甲基硅基）-红霉素A-9-[O-（1-乙氧基-1-甲乙基）]肟的＂一锅法＂合成工艺。方法以9-（E）-红霉素肟为原料,在内酰胺盐酸盐的催化下,与2-乙氧基丙烯进行醚化反应,再进行硅烷化,即经＂一锅法＂得到克拉霉素关键中间体。结果与结论目标物的结构经质谱、核磁共振谱确证。该合成路线收率良好（两步总收率为88%）、环境友好,为工业化生产克拉霉素提供了一种新的方法。

Improved synthesis of clarithromycin intermediate

2′,4″-O-Bis(trimethylsilyl) erythromycin A 9-O-(1-ethoxy-1-methylethyl) oxime(1) is the key intermediate to synthesize clarithromycin,which is one of the most important macrolide antibiotics.With erythromycin A 9-O-oxime used as the starting material,2-ethoxypropene and chlorotrimethylsilane as protection agent,catalized by 1-methyl-2-piperidone hydrochloride,2′,4″-O-Bis(trimethylsilyl) erythromycin A 9-O-(1-ethoxy-1-methylethyl) oxime is synthesized in one pot through etherification and silylation.The overall yield is 88%.The superiority of this synthetic process lies in high yield and low pollution owing to the use of 1-methyl-2-piperidone hydrochloride instead of pyridine hydrochloride,and which makes it suitable for industrialized production.