Novel C-3 cyclic ether cephalosporins and their orally absorbed prodrug esters.

modified form, the Wittig cyclisation chemistry of Woodwardet al.3) and Nayler et al.4) (Scheme 1). The racemic acids (4) were converted in conventional fashion into the corresponding chloromethyl ketones (5), which were then used to alkylate the azetidinone thiol5) (6). Addition of ^-butyl glyoxylate to the derived ketone (7), followed by elaboration of the aminols (8) with thionyl chloride and 2,6-lutidine then tri-w-butylphosphine, provided the phosphoranes (9). On thermolysis in refluxing toluene these phosphoranes cleanly cyclised to the cephems (10) in high yields. As reported for the lactonyl derivatives1}, the use of tri-rc-butyl phos-