Anti-MRSA carbapenem, L-742,728, has been prepared in large quantity using the Suzuki-Miyaura cross-coupling as the key reaction. Three approaches have been examined by varying the coupling reaction between carbapenem nucleus A and side chains B, BC, and BCD, wherein BCD represents the fully elaborated side chain. The coupling of A with BCD offers the advantage of convergence and requires fewer chemical steps after installation of the thermally unstable carbapenem skeleton. This key reaction highlights the versatility and efficiency of the Suzuki-Miyaura reaction. This approach offers a general method for the preparation of the 3-aryl carbapenems, which possess strong antibacterial activity against resistant strains.(1) (a) Methicillin Resistant Staphylococcus aureus; University of (5) Previously, we reported this class of carbapenem as 2-aryl carbapenem based on the traditional numbering system in -lactam chemistry. In this report, we use the IUPAC numbering system as depicted in L-742,728 (1). (a) Greenlee, M. L.; Cama, L. D.; DiNinno, F. P.; Heck, J. V. U.S. Pat. 5034384, 1991. (b) DiNinno, F.; Dykstra, K. D.; Greenlee, M. L.; Rano, T. A.; Guthikonda, R. N.; Schmitt, S. M.; Meurer, L. C.; Cama, L. D.; Sasor, M. F.; Laub, J. B.; Rouen, G. P.; Lee, W.; Muthard, D. A.; Hammond, M. L.; Heck, J. V.; Salzmann, T. N.; Kahan, J. S.; Huber, J. L.; Sundelof, J. G.; Dorso, K.; Kohler, J.; Gerkens, L.; Pelak, B.; St. Rose, E.; Jackson, J. J.; Hajdu, R.; Kropp, H.; Hammond, G. G.; Overbye, K. M.; Silver, L. L.
