Carbapenem Antibiotics Men-10700 Synthesis And Antibacterial Activity Of Benzoyl-piperazine Compounds

The structural core of penem molecules is a hybrid of penicillin and cephalosporin structures. These hybrid p-lactam structures do not occur naturally and production of penems is an entirely synthetic process. As carbapenem, penems show broad-spectrum antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria, except Pseudomonas aeruginosa. An important property of penems is their resistance to the actions of β-lactamases(BLAs of both bacterial and mammalian origin known as dehy dropeptidase(DHP-1).Men-10700 is active against Gram-Positive and -negative bacteria, aerobes and anaerobes. It exhibits in vitro stability to most BLAs and to renal dehydropeptidase. We have synthesized the key intermediate of 2-hydroxypenem by displacement, Wittig cyclizatin, deprotection and reduction from azetidinone. Men-10700 is synthesized by the joint between the penem bicyclic nuclus and the side chain, deprotection and reduction. Some improvement is carried out in displacement and deprotection. The process is moderate and simpler to synthesis with consumption.Because infection with methicillin-resistent Staphylococcus aureus(MRSA) have been an increasingly serious clinical problem, some scientist always try to study and discover the new drug of the higher activity ot anti-MRSA. We designed and synthesized a series of penems with 2-phenacyl Piperazine, and measured their vitro activity.We also tried to synthesize 2-ethylthio penem, another key intermediate of sulopenem. And some side chains containing pyrrole were synthesized, whick are always used in carbapenem and penem.92 compounds and intermediates were synthesized, of which 42 compounds were previously unreported.