Traceless Staudinger Ligation To Introduce Chemical Diversity on beta-Lactamase Inhibitors of Second Generation

We explored the traceless Staudinger ligation for the functionalization of the C2 position of second generation beta-lactamase inhibitors based on a diazabicyclooctane (DBO) scaffold. Our strategy is based on the synthesis of phosphine phenol esters and their ligation to an azido-containing precursor. Biological evaluation showed that this route provided access to a DBO that proved to be superior to commercial relebactam for inhibition of two of the five beta-lactamases that were tested.