Efforts toward the total synthesis of quinine, synthesis of largazole analogs, and progress toward potential biosynthetic intermediates of taxol

2012 Summer.Includes bibliographical references.Herein we discuss our work involving three different projects, namely (1) efforts toward the total synthesis of quinine, (2) synthesis of largazole analogs, and (3) progress toward potential biosynthetic intermediates of taxol. Our efforts toward the synthesis of quinine have led us toward a route toward a pipecolic acid derivative that was further elaborated to a late-stage intermediate. Following an intramolecular cyclization and deoxygenation protocol, a formal synthesis of quinine could be realized. In the second project, we have successfully synthesized and tested analogs of the known HDAC inhibitor, largazole. These analogs have demonstrated good potency towards a series of HDAC isoforms. In the third project, efforts have been made to synthesis potential biosynthetic intermediates of taxol. Utilizing highly oxygenated intermediates isolated from the heartwood of the Japanese yew tree, we have explored the reactivities of these complex natural products in hope of devising a method to construct mono-acetylated derivatives