The cycloaddition reactions of isocyanates, carbenes, and nitrenes with substituted allenyl sulfides will be used to generate Alpha-alkylidene-Beta-lactams, methylenecyclopropanes, and methyleneaziridines respectively. The Beta-lactams will be used to prepare mechanism-based monocyclic Beta-lactamase inhibitors. The alkylidene functionality will serve a key role in stabilizing the initial acyl-enzyme intermediate. Alpha-Vinylidene (i.e. exocyclic allenyl) Beta-lactams will also be preapared and tested (for Beta-lactamase inhibitory activity) as their Nu-sulfonate derivatives. Highly strained methylenecyclopropanes and methyleneaziridines will be generated via the intramolecular addition of carbenes and nitrenes to selected allenes. The expected trimethylenemethane-type intermediates thereby produced will be intramolecularly trapped generating useful bi- and tricyclic systems. Chiral allenyl sulfoxides will be prepared via 2,3-sigmatropic rearrangement of the readily available chiral propargylic alcohols. These materials will be used to prepare chiral Beta-lactams and to explore the configurational stability of allenyl anions.
| Buynak, J D; Wu, K; Bachmann, B et al. (1995) Synthesis and biological activity of 7-alkylidenecephems. J Med Chem 38:1022-34 |
