A Simple Efficient Synthesis of [23,24]-13C2-Labeled Bile Salts as NMR Probes of Protein–Ligand Interactions

The synthesis of [23,24]-13C2-labeled bile salts is achieved through a steroidal side chain degradation and isotopic regeneration strategy. Three common bile acids were degraded to the corresponding C22 aldehyde by an oxidative decarboxylation followed by ozonolysis. The side chain was subsequently regenerated via a Horner–Emmons reaction using an ylide generated from 13C2-labeled bromoacetic acid. These compounds were used as probes of protein–bile salt interactions using two- and three-dimensional NMR techniques.