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

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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[7.2.0.0^<3.8>]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.
公益社団法人日本薬学会の論文
2000-05-01