培美曲塞二钠的合成研究进展

Advances in Synthesis of Pemetrexed Disodium

介绍了合成新型抗癌药物培美曲塞二钠的两种方法。一种是以对溴苯甲酸为起始原料经酯化、缩合、溴代、环合、成盐等反应合成目标化合物,总收率达13.9%。另一是对碘苯甲酸甲酯与3-丁烯醇反应后溴代得4-(3-溴-4-氧代丁基)苯甲酸甲酯,与2,4-二氨基-6-羟基嘧啶反应后,再经水解得重要中间体2-氨基-4-氧代-5-[2-(4-羧基苯基)乙基]-4,7-二氢-3H-吡咯并(2,3-d)嘧啶,最后与L-谷氨酸二乙酯盐酸盐酰化、水解得培美曲塞二钠,总收率为16%。

There are two methods which to synthesize pemetrexed disodium, a novel anti-cancerogenic drug. Pemetrexed disodium was prepared via esterification, condensation, bromination, cyclization reaction and so on. The overall yield was 13.9%. The other method is Pemetrexed that was synthesized from methyl 4-iodobenzoate to afford 4-（4-oxobutyl）benzoic acid methyl ester, which was subjected to bromination with isopropylidene dibromomalonate, and subsequent to cyclization with 2,4-diamino-6-hydroxyprimidine, hydrolysis to give 2-amino-4, 7-dihydro-4-oxo-5-[2-（4-carboxyphenyl）ethyl]-i H-pyrro- lo（2,3-d）pyrimidine, followed by condensation with L-glutamic acid diester, and hydrolysis to give pemetrexed disodium in an overall yield 16%.