Synthesis of a Reaction Intermediate Analogue of Biotin-Dependent Carboxylases via a Selective Derivatization of Biotin

An efficient and practical synthesis of 1, a unique reaction intermediate analogue of biotin-dependent carboxylases, is described. The synthesis features a selective acylation of the 1‘-N of biotin. Target 1 inhibits the activity of the biotin carboxylase component of acetyl CoA carboxylase. It is the first known biotin-derived inhibitor of biotin carboxylase and should promote new kinetic and structural studies of the biotin-dependent carboxylases.