Stereocontrolled synthesis of piperidine-condensed tricyclic carbapenems (5-azatrinems) and their antibacterial activities.

摘要: Stereocontrolled synthesis of tricyclic carbapenem (5-azatrinem) derivatives 4, in which a piperidine ring is condensed to the skeleton, was achieved. The pivotal intermediate 2, allyl (8S,9R,10S)-5-(tert-butoxycarbonyl)-10-(R)-1-(tert-butyldimethylsilyl oxy)ethyl]-11-oxo-1,5-diazatricyclo[7.2.0.0(3,8)]undec-2- ene-2-carboxylate, synthesized starting from an acetoxyazetidinone chiron 6 practical manner based on C-C bond formation reaction between and piperidinone-ester 5, palladium-catalyzed de(allyloxy)carbonylation 7b Wittig-type cyclization via oxalimide 9. Selective deprotection N-Boc group 2 found proceed smoothly by treatment with trimethylsilyl trifluoromethanesulfonate 2,6-lutidine give amino compound 3, whose functionalization nitrogen atom 10 followed led various 5-azatrinem acids 4. These compounds showed potent vitro activities against gram-positive gram-negative bacteria.