Study On The Synthesis Of Panipenem

Panipenem has a strong antimicrobial activity and broad antibacterial spectrum, which has various use in the Clinical infection treatment.This paper was focus on the synthesis of side-chain and panipenem. Firstly, the main cy-cle was synthesized with 68% overall yield from the starting materials. Diazotization of ethyl acetoacetate, coupling with 4-AA, decomposing diazotization with Rh(OAc)2 gave the main cycle of panipenem. Secondly, two ways were researched in the synthesis of the side-chain of the panipenem. phosphoryl as amino protecting group was used in the synthesis of side-chain of panipenem. The first way is:(R)-3-hydroxy pyrrolidine reacted with diphenyl chlorophosphate to give protected (R)-3-hydroxy pyrrolidine, which further reacted with methylsulfonyl chloride to obtain the methanesulfonate, the ester was substituted with potassium ethanethioate, the subsequent hydrolization offer the final side chain with 66.5% overall yield from the starting materials. The other method is protection of ethyl acetimidate with diphenyl chlorophosphate, the obtained product reacted with (R)-3-hydroxy pyrrolidine to give the protected acetimidate compound. The chiral acetimidate pyrrolidine derivative was reacted as the first way of the synthesis of side-main to give the final side main product in the total yield of 40.6%.Finlly, the mother nucleus 6 respectively reacted with the compound 10 and 16 in the presence of diisopropylamine and diphenyl chlorophosphate to gain the compound 17 and 19 with 75% and 73% yield, different conditions and methods in the deprotection of 17 and 19 to synthesize the final product panipenem are researching in the lab.