Enabling Technology: Asymmetric Synthesis of ENT-03 Enabled by Hydrogenation High-Throughput Experimentation

ENT-03 was predicted to be the mammalian equivalent of trodusquemine, based on knowledge of the bile acids produced in mammals, such as 7-HOCA. The individual C-25 isomers of ENT-03 were prepared and both detected in mouse brain. Trodusquemine and ENT-03 have both demonstrated dramatic effects in obesity and insulin resistance. (25S)- ENT-03 was selected for development for the treatment of diabetes and obesity.