SYNTHESIS OF CARBACEPHEMS FROM SERINE

Carbacephems have been synthesized from D-serine by two routes involvi ng construction first of the six-membered ring followed by cyclization to give the bicyclic beta-lactam. In one route, alkylation of a lacti m ether was accomplished with Ni(Acac)(2) as a catalyst. The desired R stereochemistry at the carbon corresponding to C-6 of the cephem was obtained by stereospecific hydrogenation of a vinylogous carbamate. Th e second route involved a stereospecific Michael cyclization to give t he same C-6 stereochemistry. Closure of a piperidyl beta-amino acid in termediate common to both routes was accomplished using a modified Muk aiyama reagent found to be superior in our system to the traditional r eagent. The resulting carbacephem core was stereospecifically substitu ted at C-7 with an ethyl or amino functionality. The ethylated interme diate was transformed into a stable enol triflate useful for the furth er elaboration of biologically important carbacephems.