Synthesis of esters of the potent anti-bacterial trinems and analogues

Abstract

Coupling the silyl enol ether 5 and the β-lactam 9(R = Me₃Si) affords the ketones 13a–d. Compounds 13a, 13c and 13d are converted into the tricyclic lactams 16–20, 23–25. (Chemoenzymatic synthesis of optically pure silyl enol ether 5 gave access to homochiral lactams 23–25.) In addition the ketoazetidinones 13 are protected as the 1,3-oxazanes 30. A hydroxyethyl moiety is introduced into these oxazanes at C-11 with the desired stereochemistry using the Bouffard methodology, to afford the alcohols 32. Formation of the corresponding nitrobenzyl carbonate, deprotection and oxidation furnishes the ketones 35a and 35b, which are subsequently converted into the trinems 41a and 41b, respectively.