Syntheses And In Vitro Activities Of Faropenem And Noval 2-Substituted Penems

Since the first disclosure of penem antibiotics by Woodward, these compounds which have both broad antibacterial spectra, including Gram-positive and Gram-negative species and stability to various β -lactamases have received much attention as potential therapeutic agents. Faropenem(Sun-5555)is the first at present the only Penem on the market. It is a new oral and injectable penem that shows broad-spectrum antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria, except Pseudomonas aeruginosa.Sun-5555 is highly stable to various beta-lactamase and to renal dehydropeptidase-I(DHP-I). In contract to carbapenem antibiotics it have shown the prviledge of the higher safety, lower toxicity to the renal and centronerve. it is the first drug of being selected in curing the mediate bacterial infection.We have synthesized faropenem by fouteen steps from the material of 6-APA.We studied three synthetic methods of the P(0Et)₃ Wittig induced cyclization. Base on the reaction mechanism we select the method of adding the hydroquinone as the catalyst to accelerate the yield.In the process of removal of the TBDMS group from the hydroxyethyl side chain , we have investigated two synthetic methods. We gained the higher yield with the process which provides soft condition for the sensitive penems.