The Total Synthesis of Mubiroine C and Derivatives

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The dendrobine-type alkaloids are a structurally intriguing family of natural products. This class of molecules has promising neuropharmacological activities and hence, a concise yet flexible route that allows for rapid variation to probe chemical reactivity will be of great importance for further testing and evaluation. This proposal will outline the first enantioselective synthesis of mubironine C. Following the successful development of this strategy for the synthesis of mubironine C, additional natural and synthetic dendrobine- type analogs will be prepared for biological screening. The specific aims are this proposal include the following: 1. Synthesize the pyrrolidine core of mubironine C by a novel pericyclic cascade reaction. 2. Complete the first synthesis of mubironine C by a route that allows for chemical diversity in the highly functionalized six-membered ring. More specifically, this route will involve the late-stage incorporation of the six-membered ring of mubironine C using a ring-closing metathesis/olefin reduction sequence. 3. Apply the synthetic protocol towards mubironine C to the preparation of various dendrobine-type alkaloid analogs. Then, evaluate the structure-activity relationship of these molecules and elucidate the mode of action of mubironine C. [unreadable] [unreadable] [unreadable]