| abstract |
The present invention provides methods of making compounds of the structure [Q - L1] - L - [L2 - B], wherein Q is a quinolone moiety; B is a beta-lactam moiety; L, L?1, and L2¿ together comprise a carbamate-containing linking moiety, comprising the steps of: 1) reacting a lactam compound of the formula B-L4-H with phosgene to form an intermediate compound of the formula B-L4-C(=O)-Cl, where L4 is oxygen; and 2) coupling said intermediate compound with a quinolone compound of the formula Q-l3-R44, wherein L3 is nitrogen; R44 is hydrogen, Si(R45)3, or Sn(R45)3; and R45 is lower alkyl. Preferably, the process additionally comprises steps prior to the reacting and coupling steps where esters of the lactam and quinolone compounds are made. Also preferably, the coupling step comprises adding a solution containing the quinolone compound to a solution containing the intermediate compound. The process steps are also preferably performed at a temperature of from about -80 °C to about 0 °C. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem. |