1. Enantioselective synthesis of (10S)- and (10R)-methyl-anandamides
- Author
-
Alexandros Makriyannis, Marsha R. D'Souza, and Spyros P. Nikas
- Subjects
chemistry.chemical_classification ,Stereochemistry ,Organic Chemistry ,Enantioselective synthesis ,Total synthesis ,Peptide ,Anandamide ,Biochemistry ,Partial hydrogenation ,Hydrolysis ,chemistry.chemical_compound ,Stereospecificity ,chemistry ,Drug Discovery ,Wittig reaction - Abstract
For the development of novel endocannabinoid templates with potential resistance to hydrolytic and oxidative metabolism, we are targeting the bis-allylic carbons of the arachidonoyl skeleton. Toward this end, we recently disclosed the synthesis and preliminary biological data for the (13S)-methyl-anandamide. We report now the total synthesis of the (10S)- and (10R)-methyl-counterparts. Our synthetic approach is stereospecific, efficient, and provides the analogs without the need for resolution. Peptide coupling, P-2 nickel partial hydrogenation, and cis-selective Wittig olefination are the key steps.
- Published
- 2012