β-内酰胺酶抑制剂——他唑巴坦酸的合成

The Synthetic Process of Tazobactam—a β-Lactamase Inhibitor

他唑巴坦是新颍的 β 内酰胺酶抑制剂 ,以 6 APA为原料 ,经重氮化、溴代等反应制得关键中间体青霉烷酸二苯甲酯 1α 氧化物 (4) ,与 2 巯基苯并噻唑缩合后 ,经氯代得 2 β 氯甲基 2α 甲基 6,6 二氢青霉烷酸二苯甲酯 (6) ,该中间体再经缩合、氧化等步骤得到他唑巴坦酸 ,总收率 1 6 3%。该法原料易得 ,反应条件温和 ,后处理方便 。

A convenient synthesis of tazobactam,a new β lactamase inhibitor,was described starting with 6 aminopenicillanic acid,which was converted to benzhydryl penicillanate 1α oxide via diazotization,bromination,oxidation with activated magnesium dioxide in the presence of benzophenone hydrazone and reductive debromination.Then heating with 2 mercaptobenzothiazole,chlorination with sulphuryl chloride gave the 2 β chloromethylpenam.The reaction with 1H 1,2,3 triazole,oxidation with potassium permanganate gave benzhydryl 2β 〔(1,2,3 triazol 1 yl)methyl〕 2α methylpenam 3α carboxylic acid 1,1 dioxide.The deprotection by m cresol gave tazobactam.The process has the advantages of mild reaction,low cast and convenient aftertreatments.The overall yield was 16 3%.