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

DOI: 10.1248/cpb.48.716

Source and publish data:

Chemical and Pharmaceutical Bulletin p. 716 - 728 (2000)

Update date:2022-08-03

Topics:

Authors:

Mori, Makoto

Somada, Atsushi

Oida, Sadao

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Article abstract of DOI:10.1248/cpb.48.716

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 formation 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.