New straightforward synthesis and characterization of a unique 1β-methylcarbapenem antibiotic biapenem bearing a σ-symmetric bicyclotriazoliumthio group as the pendant moiety

Biapenem 1, (1R,5S,6S,)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate, is a new non-natural 1 beta-methylcarbapenem antibiotic which exhibits a wide range of antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Mercaptobicyclotriazolium chloride 2 useful for the pendant moiety of 1 was successfully synthesized starting from hydrazine hydrate 3 along an economically available synthetic route. The thiol 2 was efficiently exploited for an expeditious synthesis of biapenem 1. Characterization (crystal structure, nonbonded S---O interaction, conformational analysis, and CH- - -O hydrogen bonds) of 1 was investigated by its X-ray crystallographic, H-1 NMR, and deuteration experiment analyses.