治疗良性前列腺增生药物非那甾胺的合成  

Synthesis of Finasteride for the Treatment of BPH

作　　者：李效军[1] 王静[1] 王晓季[2] 陈立功[2] 

机构地区：[1]河北工业大学化工学院,天津300130 [2]天津大学药物科学与技术学院,天津300072

出　　处：《河北工业大学学报》2003年第6期35-38,共4页Journal of Hebei University of Technology

摘　　要：非那甾胺是一种竞争型5α-还原酶抑制剂,用于良性前列腺增生的临床治疗已逾10年.本文以孕烯醇酮为起始原料设计了新的合成路线,即孕烯醇酮经过季铵化、醇解、Op-penauer氧化、△4双键的氧化切断、氨解环合、△5双键加氢、1,2位脱氢、Bodroux反应等8步反应制得非那甾胺,而文献方法通常需要10步反应才能完成.所有的中间体及最终产物都经质谱或/和核磁共振分析确定了结构,以孕烯醇酮计总收率可达19.1％.As a substrate competition-type 5α-reductase inhibitor, Finasteride is a FDA approved medicine used for the clinical treatment of Benign Prostatic Hyperplasia for over ten years. In this paper, a novel route to the total synthesis of Finasteride from pregnenolone was proposed, thus, pregnenolone was converted to Finasteride in 8 steps, i.e. ammoniumation, alcoholysis, Oppenauer oxidation, cleavage of Δ4-double bond by oxidation, ring closure by ammonia, hydrogenation of Δ5-double bond, dehydrogenation of 1,2-position in A-ring and Bodroux reaction, while the literature methods usually involved 10 steps. The desired compounds were characterized by MS or/and NMR. The overall yield was up to 19.1% based on pregnenolone.

关 键 词：良性前列腺增生 非那甾胺 合成 结构表征 孕烯醇酮 药物设计 

分 类 号：R983[医药卫生—药品] TQ465.1[医药卫生—药学]