Synthesis of (2-mercaptoacetyl)-L-[2-14 C]tryptophan as a selective metallo-β-lactamase inhibitor via [2-14 C]indole based on chiral pool strategy.

Abstract

Metallo-beta-lactamase enzymes make bacteria resistant to a broad range of commonly used beta-lactam antibiotics. Several thiol derivatives of L-amino acids have been shown their inhibitory effects against the metallo-β-lactamase IMP-1. In this study, (2-mercaptoacetyl)-L-tryptophan as a new inhibitor of metallo-β-lactamases labeled with carbon-14 in the 2-position of the indole ring was prepared from [2-14 C]indole as a key synthetic intermediate based on chiral pool strategy. The overall synthesis was performed in 10 steps with the overall radiochemical yield 3.6% on the basis of the barium [14 C]carbonate as a starting material.