Research focuses on improving efficiency of a synthetic scheme for a small GLP-1R reverse agonist called T-0632. In previous research, base-catalyzed addition of a reduced isatin derivative to methyl acrylate generates a chiral product through a Michael addition. Only one of the two resulting enantiomers is biologically active and therefore desirable as a product. In order to eliminate the need for a chiral separation and to thus improve the efficiency of the seven-step synthetic scheme, our research has focused on designing an asymmetric Michael addition to generate the single desired enantiomer of the T-0632. Use of a bulky chiral acrylic acid ester has resulted in the production of only one of the two possible T-0632 esters. Details of this synthesis, and comparison with the use of other chiral auxiliaries for the generation of a stereospecific product in this reaction will be provided.

Asymmetric Michael additions for synthesis of a chiral GLP-1R reverse agonist

245th National Meeting (2013)

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