SM-197436

Chemical Name: (1R,5S,6S)-2-[4-(2,5-Dihydro-1H-pyrrol-3-yl)thiazol-2-ylsulfanyl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid
项目整合开发状态: Preclinical
项目研究机构: Roche (Originator), Sumitomo Pharmaceuticals (Originator)
合成路线:Michael addition of ethyl acrylate (I) to glycine ethyl ester (II) produces the amino diester (III),which is protected as the allyl carbamate (IV) by treatment with allyl chloroformate.Dieckmann cyclization of diester (IV) in the presence of NaH leads to pyrrolidinone (V).After reduction of (V) to the corresponding alcohol (VI) with NaBH4,dehydration by means of methanesulfonyl chloride and pyridine furnishes the conjugated ester (VII).Acid (VIII),obtained by alkaline hydrolysis of (VII),is then condensed with magnesium tert-butyl malonate in the presence of CDI to produce keto ester (IX).Chlorination of (IX) with sulfuryl chloride,followed by acidic decarboxylation gives rise to chloro ketone (X).This is then condensed with ammonium dithiocarbamate to generate the 2-mercapto thiazole (XI)

合成路线:Coupling of the carbapenem phosphate (XII) with mercaptothiazole (XI) furnishes thioether (XIII).Finally,desilylation of (XIII),followed by palladium-catalyzed removal of the allyl ester and carbamate groups provides the title compound