消旋15-甲基-前列环素钠盐的合成

Synthesis of D, L-15-methylprostacyclin Sodium Salt

前列环素（PGI2）是抑制血小板聚集作用最强的内源性物质,并具有较强的舒张血管作用。国外报道,PGI2用于心、肺旁路手术及肾病患者的过炭输血过程中防止血小板聚集,对难产胎儿的血循环受阻,外周血管病、心肌梗塞前的心绞痛和中风等均有治疗作用。 PGI2在中性或酸性条件下,极不稳定,易自动转化为无效的6-酮-PGF1α,因此药用其钠盐。PGI2生物半衰期3～4分钟,在体内可经多种途径失活。

Synthesis of d , 1-(15S)-15-methylprostacyclin sodium salt (4a) , its 15-epimer (4b) and d ,1-(15R)-15-methyl-6-keto-prostaglandin F1α (5) were reported.d,1-(15S)-15-methyl-(5R,6R)-5-iodoprostaglandin I1 methyl ester (2a) and d,1-(15S)-15-methyl- (5S,6S)-5-iodoprostaglandin I1 methyl ester (3a) were prepared from the reaction of d,1-(15S)-15-methylprostaglandin F2α methyl ester (1a) with iodine. The reaction of a mixture of (2a) and (3a) with sodium methoxide followed by saponification with sodium hydroxide gave d,1-(15S)-15-methylprostacyclin sodium salt (4a) .By similar methods, (4b) was obtained from (lb) . Hydrolysis of (4b) gave d,1- (15R) -15-methyl-6-ketoprostaglandin F1α (5) .