红霉素A肟的新合成方法

Novel method for the synthesis of erythromycin A oxime

目的用一种全新的方法合成红霉素A肟 (1)。方法在酸碱缓冲溶液中由红霉素A(3 )与盐酸羟胺缩合生成 1。系统研究了反应体系的 pH值、反应温度以及盐酸羟胺的加入量对反应结果的影响。同时对红霉素A肟化反应机理进行了推导。结果红霉素A 9 肟的收率达 95 %以上 ,产品纯度达 92 %。化合物 1经红外、氢谱、碳谱、质谱鉴定 ,与文献报道相一致。结论该方法有效地抑制了红霉素A的酸性分解 ,与文献方法相比 ,大幅度提高了反应的收率和产品的纯度。

Aim To synthesize erythromycin A 9 oxime(1)which is the common intermediate of some novel antibiotics such as clarithromycin,azithromycin,rozithromycin,flurithromycin and dirithromycin by a novel method.Methods The target compound(1)was prepared from erythromycin A(3)and hydroxylamine hydrochloride in a novel acid base buffer.The relationships of the purity of compound 1 and the pH,the reactive temperature and the quantity of hydroxylamine hydrochloric were studied.The mechanism of oximation reaction of erythromycin A was deduced.The main impurity,which is 8,9 dehydro erythromycin A 6,9 hemiketal(2) and involved in the synthesis of erythromycin oxime was separated and purified.Results The yield and purity of 1 were more than 95% and 92% respectively.The mass spectra,infrared spectra and complete proton and carbon NMR of compounds 1 and 2 were consistent with the results reported by literatures completely.Conclusion The acid base buffer can prevent greatly the decomposition of erythromycin A.The yield and purity of 1 were increased by the novel method.