匹伐他汀钙合成工艺改进  

Improved Synthetic Process of Pitavastatin Calcium

作　　者：李振华[1] 张巧娜[1] 钟为慧[1] 

机构地区：[1]浙江工业大学药学院绿色制药技术与装备教育部重点实验室,浙江杭州310014

出　　处：《中国医药工业杂志》2017年第4期499-502,共4页Chinese Journal of Pharmaceuticals

摘　　要：以(3R,5S)-3,5,6-三羟基-3,5-O-亚异丙基己酸叔丁酯(6)为原料,经氧化、与匹伐他汀母核的膦叶立德试剂缩合、脱保护成内酯、水解、成盐等5步反应合成降血脂药物匹伐他汀钙,中试生产总收率34.3%。其中,关键中间体(3R,5S)-6-氧代-3,5-二羟基-3,5-O-亚异丙基己酸叔丁酯(3)的合成,以三氯异氰脲酸/4-羟基-2,2,6,6-四甲基哌啶氮氧化物(TCCA/TMHPO)氧化体系代替Swern氧化体系,反应条件温和,产物质量提高。In this paper, t-butyl （3R,5S）-3,5-O-isopropylidene-3,5,6-trihydroxyhexanoate（6） was subjected to oxidation, condensation with ylide reagent of nuclear parent, deprotection for forming lactone, hydrolysis and salification to give lipid regulating drug, pitavastatin calcium, with a total yield of 34.3% in pilot-scale test. In the synthesis of the key intermediate t-butyl （3R,5S）-6-oxo-3,5-O-isopropylidene-3,5-dihydroxyhexanoate（3）, the oxidation was carried out with trichloroisocyanuric acid/4-hydroxyl-2,2,6,6-tetramethylpiperidine nitroxides（TCCA/TMHPO） instead of Swern oxidationsystem, making this progress more attractive in terms of milder reaction conditions and improved product quality.

关 键 词：匹伐他汀钙 合成工艺 三氯异氰脲酸/4-羟基-2 2 6 6-四甲基哌啶氮氧化物(TCCA/TMHPO) 氧化 

分 类 号：R972.6[医药卫生—药品]