Synthesis of 5,6-cis-carbapenems related to C-19393 H2

Abstract
The synthesis of 6,7-cis-7-(1-hydroxy-1-methylethyl)-3-oxa-1-azabicyclo[4.2.0]octan-8-ones (3a, b), key intermediates for the preparation of the 5,6-cis-carbapenem antibiotic C-19393 H2{sodium (5R, 6R)-3-[(E)-(2-acetamidoethenyl)-(R)-sulphinyl]-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylate}(1a) and its derivatives, was investigated. Sulphenylation of the 3-oxa-1-azabicyclo[4.2.0]octan-8-ones (2a, b), followed by the aldol reaction with acetone, gave the 7-(1-hydroxy-1-methylethyl)-7-sulphenyl derivatives (7a—e). Reductive desulphurization of compounds (7a—e) with an organotin hydride (tri-n-butyltin hydride or triphenyltin hydride) in the presence of a radical initiator gave rise to stereoselective formation of the cis-azetidinones (3a, b). A total synthesis of (±)-C-19393 H2(1a) and its derivatives having other substituents at the C (3) position, (1b—e), starting from (3a, b)via a carbene insertion reaction, is also described.