1) The trans-esterification of methyl acetoacetate (I) with allyl alcohol (II) gives the allyl ester (III), which is treated with p-toluenesulfonyl azide (IV) and triethylamine in acetonitrile to yield the diazo derivative (V). The reaction of (V) with tert-butyl-dimethylsilyl triflate (VI) and triethyl amine in dichloromethane affords the enol silyl ether (VII), which is condensed with 3-[1-(tert-butyldimethyl-silyloxy)ethyl-4 acetoxyazetidin-2-one (VIII) by means of ZnCl2 in dichloromethane giving 3-[l-(tertbutyldimethylsilyloxy)ethyl]-4-(4-allyloxy-3-diazo-2,4-dioxobutyl)azetidin-2-one (IX). The cyclization of (IX) by means of rhodium acetate in refluxing benzene yields allyl 6alpha-[l(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (X), which is condensed with 2-(mercaptomethyl)pyridine (XI) by means of diphenyl chlorophosphate and diisopropylamine in acetonitrile affording allyl 6alpha-[l(R)-hydroxy-ethyl]-2-(2-pyridylmethylthio)carbapen-2-em-3-carboxylate (XII). The hydrolysis of (XII) with tetrakis-triphenylphosphine-palladium, triphenylphosphine and potassium 2-ethylhexanoate in dichloromethane gives the potassium salt (XIII), which is finally quaternized with methyl triflate and p-toluenesulfonic acid in acetone.

2) The condensation of 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (XIV) with diphenyl chlorophosphate as before gives 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-(2 pyridyl-methylthio)carbapen-2-em-3-carboxylate (XV), which is quaternized with methyl iodide in acetone to afford the quaternized ester (XVI). Finally, this compound is deprotected by hydrogenolysis with H2 over Pd/C in basic THF.

1) The trans-esterification of methyl acetoacetate (I) with allyl alcohol (II) gives the allyl ester (III), which is treated with p-toluenesulfonyl azide (IV) and triethylamine in acetonitrile to yield the diazo derivative (V). The reaction of (V) with tert-butyl-dimethylsilyl triflate (VI) and triethyl amine in dichloromethane affords the enol silyl ether (VII), which is condensed with 3-[1-(tert-butyldimethyl-silyloxy)ethyl-4 acetoxyazetidin-2-one (VIII) by means of ZnCl2 in dichloromethane giving 3-[l-(tertbutyldimethylsilyloxy)ethyl]-4-(4-allyloxy-3-diazo-2,4-dioxobutyl)azetidin-2-one (IX). The cyclization of (IX) by means of rhodium acetate in refluxing benzene yields allyl 6alpha-[l(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (X), which is condensed with 2-(mercaptomethyl)pyridine (XI) by means of diphenyl chlorophosphate and diisopropylamine in acetonitrile affording allyl 6alpha-[l(R)-hydroxy-ethyl]-2-(2-pyridylmethylthio)carbapen-2-em-3-carboxylate (XII). The hydrolysis of (XII) with tetrakis-triphenylphosphine-palladium, triphenylphosphine and potassium 2-ethylhexanoate in dichloromethane gives the potassium salt (XIII), which is finally quaternized with methyl triflate and p-toluenesulfonic acid in acetone.

2) The condensation of 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (XIV) with diphenyl chlorophosphate as before gives 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-(2 pyridyl-methylthio)carbapen-2-em-3-carboxylate (XV), which is quaternized with methyl iodide in acetone to afford the quaternized ester (XVI). Finally, this compound is deprotected by hydrogenolysis with H2 over Pd/C in basic THF.

2) The condensation of 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (XIV) with diphenyl chlorophosphate as before gives 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-(2 pyridyl-methylthio)carbapen-2-em-3-carboxylate (XV), which is quaternized with methyl iodide in acetone to afford the quaternized ester (XVI). Finally, this compound is deprotected by hydrogenolysis with H2 over Pd/C in basic THF.