摘要
21-乙酰氧基孕甾-1,4,9(11),16-四烯-3,20-二酮(2)经高锰酸钾氧化得16α,17α-二羟基孕甾-21-乙酰氧基-1,4,9(11)-三烯-3,20-二酮(3),收率由文献的89.7%提高至92.2%;以N-溴代琥珀酰亚胺代替文献的1,3-二溴-5,5-二甲基海因作溴代试剂,3经溴代得9α-溴代-11β,16α,17α-三羟基孕甾-21-乙酰氧基-1,4-二烯-3,20-二酮(4),转化率由99.0%提高至99.8%以上;4在锌粉和催化剂六水合三氯化铬作用下脱溴得11β,16α,17α-三羟基孕甾-21-乙酰氧基-1,4-二烯-3,20-二酮(5),减少了铬试剂用量,降低了重金属残留风险;同时简化了精制步骤,收率由文献的67.9%提高至75.3%。5再经水解、缩合制得布地奈德(1),总收率48.2%(以2计)。
21-Acetoxypregna- 1,4,9,16-tetraene-3,20-dione （2） was oxidized by potassium permanganate to give 16α,17α-dihydroxypregna-21-acetoxy- 1,4,9 （11） -triene-3,20-dione （3） with a yield of 92.2 % . Then 9α-bromo- 11 13,16α, 17ct-trihydroxypregna-21-acetoxy- 1,4-diene-3,20-dione （4） was synthesized via bromination of 3 with a conversion rate of 99.8 % with N-bromosuccinimide instead of 1,3-dibromo-5,5-dimethylhydantoin. Then 1113,16α, 17α- trihydroxypregna-21-acetoxy-l,4-diene-3,20-dione （5） was prepared via debromination of 4 in the presence of zinc powder and chromium chloride hexahydrate with a yield of 75.3 % . In this step, the dose of chromic reagent was decreased from 13 % to 5 %, so that the risk of heavy metal residue was reduced. Then 5 was subjected to hydrolysis and condensation to prepare budesonide with an overall yield of 48.2 % （based on 2）.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第8期1111-1114,共4页
Chinese Journal of Pharmaceuticals
关键词
布地奈德
孕甾
过敏性哮喘
氧化
脱溴
六水合三氯化铬
budesonide
pregane
allergic asthma
oxidation
debromination
chromium chloride hexahydrate
