Progress toward the total synthesis of hypocrellin A via a copper-catalyzed asymmetric biaryl coupling reaction

ORGN 192

Erin M. O'Brien, erinmo@sas.upenn.edu, Carol A. Mulrooney, cmulroon@sas.upenn.edu, Xiaolin Li, and Marisa C Kozlowski, marisa@chem.upenn.edu. Department of Chemistry, University of Pennsylvania, 231 S 34th St Box 160, Philadelphia, PA 19104
The structurally complex perylenequinones comprise a family of natural products that possess potentially important photoactivatable anticancer profiles. Hypocrellin A, a member of this family, is currently in first stage clinical trials for the treatment of prostate cancer. Nevertheless, an enantioselective synthesis of this molecule has yet to be achieved. The Kozlowski group has developed a 1,5-diaza-cis-decalin ligand that provides high enantioselectivity in the copper-catalyzed asymmetric biaryl coupling reaction. This reaction, when applied to a highly substituted naphthol, yields a chiral biaryl that can subsequently be functionalized to a perylenequinone. Specifically, efforts toward Hypocrellin A will be outlined. Synthesis of the functionalized naphthol, introduction of the C7/C7' functionalized side chain, and efforts toward the formation of the seven-membered ring via a kinetically diastereoselective intramolecular aldol reaction will be presented.