6α-溴青霉烷酸-1-氧化物对硝基苄酯的制备

Synthesis of p-Nitrobenzyl 6α-Bromopenicillanate-1-oxide

6α氨基青霉烷酸经重氮化、溴化转变为6α溴代青霉烷酸,在双氧水与苯酚存在的情况下被氧化为6α溴青霉烷酸1氧化物,再使用对硝基溴化苄保护6α溴青霉烷酸1氧化物中的3位羧基,生成6α溴青霉烷酸1氧化物对硝基苄酯。该方法操作简便,条件温和,总收率达58.6%。探讨了氧化及保护的反应条件。其中第3步反应收率比文献提高了2%,并且首次使用超声波促进反应,使反应时间缩短了16h。

6α-Bromopenicillanic acid was conveniently prepared from 6-aminopenicillanic acid （6-APA） by diazotization, bromination, then it was converted into 6α-bromopenicillanic acid 1-oxide by the oxidant of 30% hydrogen peroxide in phenol. Esterification of 6α-Bromopenicillanic acid 1-oxide by p-nitrobenzyl bromide gave p-nitrobenzyl 6α-bromopenicillanate-l-oxide with a total yield of 58.6%. The synthetic process was convenient, and it could be carried out under a mild condition. The optimal conditions of oxidation and protection were discussed. And the yield of p-nitrobenzyl 6α-bromopenicillanate-l-oxide from 6α-bromopenicillanic acid was increased by 2% , more than that cited in literatures. Ultrasonic technique was used firstly to promote this reaction as a resuh the reaction time was reduced by 16 hours.