合成路线1

The Grignard condensation of the chiral pyrrolidinone (I) with 4-(dimethoxymethyl)phenylmagnesium bromide (II) in THF, followed by reduction with NaBH4, gives the aminoalcohol (III), which is cyclized to the pyrrolidine (IV) by means of MsCl and TEA in dichloromethane. Hydrolysis of the dimethyl acetal of (IV), followed by separation of the resulting diastereomeric mixture of aldehydes, yields the desired diastereomer (V). The reduction of (V) with NaBH4, followed by reaction with Ms-Cl in dichloromethane, affords the mesylate (VI), which by reaction with methylamine provides the secondary amine (VII). The protection of (VII) with allyl chloroformate and TEA, cleavage of the silyl-protecting group gives the hydroxy pyrrolidine (VIII), which is treated with MsCl and TEA to yield the mesylate (IX). The reaction of (IX) with potassium thioacetate in hot DMF affords the sulfanyl pyrrolidine (X), which is condensed with the penem diphenyl phosphate (XI) by means of DIEA in acetonitrile to provide the protected intermediate (XII). Finally, (XII) is converted into the target compound by reaction with PdCl2(PPh3)2 and Bu3SnH in dichloromethane/water.