Process for preparing 17-beta-subsituted-1-methyl-5-alpha-androst-1-en-3-ones and their derivatives

• Main Authors: HUYUE ZHANG, YAN CHEN
• Format: Patent
• Language: Chinese; English
• Published: 29.12.2004
• Edition: 7
• Subjects: CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY; STEROIDS

The present invention belongs to the field of chemical synthesis technology, and relates to preparation process of compound 17beta-substitute-1-methyl-5alpha-androst-1-alkenyl-3-ketone (methenolone) and its derivative. The present invention prepares methenolone with 17beta-acetoxy-5alpha-androst-1-alkenyl-3-ketone as material and through five reaction steps of epoxidation, hydrogenolysis, ketalization, oxidation and Gridnard reaction. The 17beta-hydroxyl may be acidated, etherified and esterified into various methenolone derivatives. The present invention has the advantages of no environmental pollution caused by diazotitation, direct alkali oxidation after epoxidation, catalytic hydrogenolysis and ketalization without separation, simple operation program, high total product yield and high product purity. 本发明属化学合成领域，涉及化合物17β-取代-1-甲基-5α-雄甾-1-烯-3-酮(美替诺龙)及其衍生物的制备方法。本发明以17β-乙酰氧基-5α-雄甾-1-烯-3-酮为原料，经环氧、氢解、缩酮化、氧化、格氏反应5步反应制得美替诺龙，17β-羟基酰化成相应的美替诺龙醋酸酯、丙酸美替诺龙、庚酸美替诺龙、十一酸美替诺龙；17β-羟基醚化成美替诺龙四氢吡喃醚；17β-羟基酯化成相应的美替诺龙甲酸酯、美替诺龙乙酸酯、美替诺龙丙酸酯、美替诺龙苯甲酸酯。本发明具有如下优点：避免了重氮化反应对环境的污染，使用环氧化和催化氢解，缩酮化反应后不经分离直接进入碱性氧化，简化操作程序，产物总收率以及纯度高。