新的前列腺癌治疗剂17-( 5′-异噁唑基 )雄甾-4,16-二烯-3-酮合成方法的改进(英文)  

Improved synthesis of 17-(5′-isoxazolyl) androst-4,16-dien-3-one,a potential agent for the treatment of prostate cancer

作　　者：苗及[1] 凌仰之[1] 雷小平[1] 李洁 

机构地区：[1]北京大学药学院药物化学系,北京100083

出　　处：《中国药物化学杂志》2002年第2期97-102,共6页Chinese Journal of Medicinal Chemistry

基　　金：ProjectsupportedbytheNationalNaturalScienceFoundationofChina(396 70 85 5)andbytheNationalInstitutesofHealth USA(CA 2 774 0 )

摘　　要：17 (5′ 异唑基 )雄甾 4 ,16 二烯 3 酮 (4,L 39)是最有希望的P4 5 0 17α和 5α 还原酶的双重抑制剂 ,对前列腺癌及前列腺肥大具有潜在的治疗作用。对其合成路线进行改进 ,收率极大提高。首先 ,Claisen缩合物 2用羟胺在乙醇中环和得到纯 5′ 异唑 3a ,用Swern氧化反应直接氧化 3a ,然后在在酸中异构化后得到L 39(4)。或者 ,化合物 2在无水甲酸中与羟胺环和得到 3 甲酯物 (6 ) ,后者以改良奥氏氧化法直接氧化生成 4 烯 3 酮物 (4)。17-(5′-isoxazolyl)androst 4,16 dien 3 one(4, L 39)is the most promising inhibitor of 17α hydroxylase/C 17,20 lyase(P450 17α )and 5α reductase(5α R),and has potential uses in the treatment of prostate cancer and benign prostatic hypertrophy Its synthesis has been improved with much higher yield in this paper First,the Claisen condensate(2)was cyclized with hydroxylamine in ethanol to give pure 5′ isoxazole 3a,which could be oxidized directly by Swern oxidation and then isomerized in acid to give L 39 (4) Second,2 was cyclized with hydroxylamine in anhydrous formic acid to give 3 formate(7),which was then oxidized directly by the modified Oppenauer oxidation to give 4 en 3 one(4).

关 键 词：17-(5'-异恶唑基)-雄甾-4 16-二烯-3-酮 前列腺癌 抑制剂 P45017α羟化酶和5α-还原酶 

分 类 号：TQ464[化学工程—制药化工]