Synthesis of biotinylated diazinon: Lessons learned for biotinylation of thiophosphate esters

Abstract Biotinylation permits recovery of a molecule from a complex mixture, with commercially available streptavidin containing products (such as streptavidin-coated beads). As part of a larger effort to evaluate reagents capable of degrading diazinon, a thiophosphate insecticide, we pursued biotinylation of this molecule. Our strategy focused on replacing a single thiophosphate ethyl ester with an ester linkage that contains biotin. Multiple approaches—using published methods—were unsuccessful and resulted in no reactivity, or degradation of starting material. Here, we report a successful strategy for the synthesis of biotinylated diazinon, which is likely applicable to alternative thiophosphate esters and other biotinylated molecules.