Abstract by Isaac Smith
Chemistry and Biochemistry
Acetamide [3 + 2] cycloaddition for the synthesis of MDR Reversal Pyrrolidinoindoles
Our group is currently working to develop a novel [3 + 2] cycloaddition reaction to form pyrrolidinoindole analogs in an efficient manner. This reaction utilizes a chiral auxiliary derived from L-phenylalanine to enhance the stereospecificity of the proposed reaction. A variety of indole substrates are currently being prepared and reacted with the chiral auxiliary acetamide to provide examples for our first publication of this method. Our method will be further explored through an asymmetric catalytic process by use of an achiral substrate. Upon completion of the reaction development with asymmetric bis-oxazoline catalysts, we will pursue the synthesis of anti-cancer nocardioazine A. Nocardioazine A was recently shown to inhibit Pgp-170, a protein overexpressed in cancer cells that removes anti-cancer drugs from the cell making them drug-resistant. Our reactions involved in the synthesis of the chiral auxiliary acetamide are performed on 2-10 g scale and reactions of the cycloaddition are performed at 10-50 mg scale. Purification of compounds is achieved through chromatography.