Approaches toward the total synthesis of Kopsia indole alkaloids

ORGN 662

Brian G. Pujanauski, bgpujanauski@berkeley.edu, Department of Chemistry, University of California, berkeley, CA 94720 and Richmond Sarpong, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720.
A number of structurally related indole alkaloids have been isolated from the Kopsia genus of flowering plants in Asia, some of which possess multi-drug resistance (MDR) reversing properties. Lunderine B, one of the members of this family, possesses MDR-reversing activity against vincristine resistant human KB cells. Our interest in developing a synthesis of compounds in this family lies in being able to produce enough of the natural products to allow the construction appropriately derivatized analogs to serve as biological probes for study of the mechanism of MDR-reversal. One of the approaches under investigation begins with a robust Ugi four-component coupling that delivers an intermediate containing all of the carbon atoms needed for lapidilectine B or lunderine B on a 200 gram scale.