ChemInform Abstract: Stereocontrolled Synthesis of Piperidine-Condensed Tricyclic Carbapenems (5-Azatrinems) and Their Antibacterial Activities.

Stereocontrolled synthesis of tricyclic carbapenem (5-azatrinem) derivatives 4, in which a piperidine ring is condensed to the carbapenem skeleton, was achieved. The pivotal tricyclic intermediate 2, allyl (8S, 9R, 10S)-5-(tert-butoxycarbonyl)-10-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-11-oxo-1, 5-diazatricyclo[7.2.0.03.8]undec-2-ene-2-carboxylate, was synthesized starting from an acetoxyazetidinone chiron 6 in a practical manner based on a C-C bond formaiton reaction between 6 and piperidinone-ester 5, palladium-catalyzed de(allyloxy)carbonylation of 7b and Wittig-type cyclization via an oxalimide 9. Selective deprotection of the N-Boc group of 2 was found to proceed smoothly by treatment with trimethylsilyl trifluoromethanesulfonate and 2, 6-lutidine to give the amino compound 3, whose functionalization on the nitrogen atom to derivatives 10 followed by deprotection led to various 5-azatrinem acids 4. These compounds showed potent in vitro activities against gram-positive and gram-negative bacteria.