Abstract
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 isomers were detected in neonatal mouse brain and liver. 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. In this paper the first synthesis of this putative natural product is described. Starting with a stereo-defined steroidal intermediate 2, the semi-synthesis involves three stereoselective steps: Horner-Emmons olefination, hydrogenation, and reductive amination. Asymmetric hydrogenation using a ruthenium coordinated Mandyphos ligand was found to be effective in controlling the C25-stereochemistry of both isomers. The syntheses of the ENT-03 isomers and a deuterated reference standard facilitated identification and quantification of this natural product in mouse tissues, and exploration of its therapeutic potential.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
