齐多夫定合成改进

An improved synthetic process of zidovudine

以胸苷为原料,5′位醇羟基用对甲氧基苯甲酸成酯保护,然后与偶氮二甲酸二乙酯和三苯基膦反应成"氧桥",再与叠氮化钠反应引入"叠氮"基团,最后脱保护得齐多夫定,总收率为67%.本法在最后一步脱保护基后用碱性去离子水除杂,用热正丁醇纯化产物,操作简单,适宜工业化生产.

Zidovudine was synthesized from thymidine.Thymidine was esterificated with 4-methoxybenzoic acid to protect its primary hydroxyl group of 5′ position and then was converted into 2,3′-anhydro-5′-o-(4-methoxybenzoyl)thymidine with diethyl azodicarboxylate and triphenylphosphine. 2,3′-anhydro-5′-o-(4-methoxybenzoyl) thymidine was treated with sodium azide to get 3′-azido-3′-deoxy-5′ -o-(4-methoxybenzoyl)thymidine, followed by 5′-o-deprotection to yield zidovudine in overall yield of 67%.After deprotection, impurities were removed with alkaline de-ionized water and zidovudine was purified by hot n-butyl alcohol. The method is simple and suitable for industrialization.