Catechol-Vanadate Analogues as β-Lactamase Inhibitors

Abstract

Studying the Mechanism of Vanadate Catechol inhibition, and the Development of New β-lactamase Inhibitors……………………………………………………...…..21 II. Materials and Methods Materials, Instrumentation, and Analysis ……………………………………….…..23 Synthesis and Characterization of dicyclohexylammonium o-phenylene phosphate (1a)…………………………………………………………………………………..24 Kinetic Experiments with 1a………………………………………………………...27 Synthesis and Characterization of o-(4-nitrophenylene) carbonate (2)……….…..28 Kinetic Experiments with 2……………………………………………………….....29 Synthesis and Characterization of o-phenylene carbonate (3)…………………...….31 Kinetic Experiments with 3………………………………………………………....32 Determination of Rate Constants……………………………………………………33 III. Results Synthesis and Characterization of dicyclohexylammonium o-phenylene phosphate (1a)…………………………………………………………………………………...35 Kinetic Experiments with 1a………………………………………………………...38 Synthesis and Characterization of o-(4-nitrophenylene) carbonate (2)……………...44 Kinetic Experiments with 2………………………………………………………….46 Synthesis and Characterization of o-phenylene carbonate (3)………………………59 Kinetic Experiments with 3………………………………………………………….61 IV. Discussion……………………………………………………………………….71 V. Conclusions and Future Work………………………………………………….75 VI. References………………………………………………………………………76 V1I. Appendix A: Synthesis of o-phenylene phosphate (1)………………..…………………...78 B: Synthesis of o-(4-nitrophenylene) carbonate (2)………………………………..85 C: Synthesis of o-phenylene carbonate (3)………………………………………...86 D: Example of an Dynafit analysis…………………………………………………..87