青霉烯和碳青霉烯类抗生素关键中间体——4-乙酰氧基氮杂环丁酮的立体选择性合成

Stereoselective Synthesis of 4-Acetoxyazetidione: the Key Intermediate of Penem and Carbapenem Antibiotics

以6,6-二溴青霉烷酸甲酯为原料经过氧化、格氏反应、还原、羟基保护、开环、甲基化、脱保护和乙酰化合成青霉烯和碳青霉烯类抗生素关键中间体4-乙酰氧基氮杂环丁酮(4-AA).该路线立体选择性非常好,避免了手性异构体的分离和重金属盐的使用,总收率30%.中间体及产品4-AA的结构均通过IR,MS,1HNMR和13CNMR确认.

The key intermediate of penem and carbapenem antibiotics 4-acetoxyazetidione （4AA） was obtained from methyl 6,6-dibromopenicillanate via oxidation, Grignard reaction, reduction, hydroxyl protection, ring opening reaction, methylation, deprotection and acetylation. This process avoided the separation of chiral isomers and the use of heavy metallic salt with an excellent stereoselectivity. The overall yield was 30%. The structures of the products were characterized by IR, MS, 1H NMR and 13C NMR techniques.