Carbapenem and penem antibiotics. VII. Synthesis and antibacterial activity of 1 beta-methyl-2-(quaternary heteroaromatic-thiomethyl) carbapenems.

The synthesis and antibacterial activity of a series of 1 beta-methylcarbapenems having quaternary heteroaromatic-thiomethyl groups at the C-2 position are described. Both 2-hydroxymethyl and 2-chloromethyl carbapenems (1 and 7) respectively served as the common key intermediates for the preparation of these compounds. Of these, the 4-pyridiniothiomethyl derivatives exhibited the best antibacterial properties and turned out to possess high in vivo efficacy as well.

Carbapenem and penem antibiotics. VI. Synthesis and antibacterial activity of 2-heteroaromatic-thiomethyl and 2-carbamoyloxymethyl 1-methylcarbapenems.

The synthesis and antibacterial activity of the 1-methylcarbapenems, 2-heteroaromatic-thiomethyl and 2-carbamoyloxymethyl derivatives having a 6-[(R)-1-hydroxyethyl] side chain, are described. The introduction of a methyl substituent at the C-1 position was accomplished by a newly developed procedure using crotyl halides and zinc dust. The 2-hydroxymethyl carbapenems as key intermediates allowed an easy entry into the preparation of title carbapenems.

Carbapenem and penem antibiotics. V. Synthesis and antibacterial activity of 2-functionalized-methyl 1-methylcarbapenems related to asparenomycins.

The synthesis of 1 alpha- and/or 1 beta-methylcarbapenems, 2-unsubstituted and 2-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl derivatives having a 1-(hydroxy)methylethylidene or cyclic carbonate side chain at the C-6 position, is described. The in vitro antibacterial activities of these compounds and their corresponding 1-unsubstituted carbapenems are compared.