Sulfur-free Penicillin Derivatives. VI. Synthesis of the 1-Oxacephem Ring System

Abstract

The title compound has been synthesized by ring closure of an alkyl 2-(2′-chloro-3′-S-phthalimido-4′-oxo)azetidinyl-3-methyl-4-hydroxy-trans-2-butenoate using SN1 experimental conditions. The required E-allylic alcohols were obtained in two ways starting with an alkyl 2-(2′-chloro-3′-S-phthalimido-4′-oxo)azetidinyl-3-methyl-2-butenoate. The first involves allylic bromination with 1 molar equiv. of N-bromosuccinimide, conversion of the mixed Z- and E-allylic bromides into the mixed Z- and E-allylic formates, and deformylation to a mixture of E-alcohol and lactone. The alcohol was separated from the lactone via its tetrahydropyranyl derivative, and then regenerated. In the second route, allylic bromination was performed with 2 molar equiv. of N-bromosuccinimide and the resulting dibromo compound was converted into the β,γ-unsaturated olefin with zinc in acetic acid. Epoxidation with peroxytrifluoroacetic acid followed by exposure to triethylamine again afforded a mixture of E-alcohol and lactone. The u.v. spectrum of a 1-oxacephem shows a maximum at 266 nm.