173241-47-9Relevant academic research and scientific papers
Enantioselective total syntheses of [6R,7R] and [6S,7S] tricyclic β-lactams
Niu, Chuansheng,Pettersson, Teresia,Miller, Marvin J.
, p. 1014 - 1022 (2007/10/03)
The reaction of Ox-glycyl chloride with a chiral imine derived from the combination of D-(R)-glyceraldehyde acetonide and protected D-threonine afforded optically active, highly functionalized cis-substituted β-lactams 11 and 12. These β-lactams provide versatile intermediates for the syntheses of biologically important carbacephalosporins, isooxacephems, and other multicyclic β-lactams. Desilylation and oxidation of 12 with Dess-Martin periodinane followed by intramolecular cyclization produced a novel tricyclic β-lactam 17 and a 1-(hydroxymethyl)-O-2-isocephem 18 with [6R,7R] absolute configuration. Removal of the Ox protecting group and acylation of 17 in a one-pot reaction followed by saponification furnished the target salt 24. Alternatively, reaction of phthaloylglycyl chloride with the chiral imine derived from the combination of L-(S)-glyceraldehyde acetonide and protected D-threonine gave only one enantiomeric azetidinone 27 in high yield. Further manipulation of 27 provided a new tricyclic β-lactam 39 with [6S,7S] absolute configuration which satisfies the stereochemistry typically required for antibacterial activity. This synthetic procedure provides a short, versatile and enantioselective method of preparing polycyclic β-lactams. Biological testing of these tricyclic β-lactams indicated that salt 39 has potential inhibitory activity against four typical strains of bacteria.
