β-内酰胺酶抑制剂——他唑巴坦新的合成方法

A New Synthesis of Tazobactam──a β-Lactamase Inhibitor

他唑巴坦 (Tazobactam)是一种新颖的 β 内酰胺酶抑制剂 ,以 6 氨基青霉烷酸为原料 ,以新的酯化、氧化反应制得关键中间体M4,M4与 2 羟基苯并噻唑缩合后 ,经氯代、成环、氧化、水解等反应得他唑巴坦 ,总产率达17.8%。该路线在酯化反应中产率达 10 0 %。用H2 O2 直接氧化 ,避免使用易爆氧化剂 ,使反应条件温和 ,易于进行工业化生产。

A new synthesis of tazobactam, a new β lactamse inhibitor, was described starting from 6 APA, first to get an intermedium M 4 by a new esterification and oxidation, which then underwent condensation with 2 mercaptoben thiazole 2 mercaptobenzothiazole, chlorination with HCl and through other reactions, such as cyclization, oxidation, hydrolysis, with an overall yield of 17.8%. The yield is 100% in esterification and H 2O 2 is used as an oxidant instead of explosive one. The process has the advantages of mild reaction, low cast and convenient aftertreatment.