Harnessing glycal -epoxide rearrangements: Synthetic efforts to adriatoxin and analogues of yessotoxin

• Main Author: Akoto, Clement Osei
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2009
• Subjects: Organic chemistry
• ISBN: 9781109070804; 1109070802

Adriatoxin was isolated from the digestive glands of mussels Mytilus galloprovincialis by Cimminiello and coworkers in 1997. A closely related toxin, yessotoxin (YTX) has exhibited potent neurotoxic action on cultured cerebellar neurons and has induced a twofold increase in cytosolic calcium. YTX displays potent cytotoxic activities against human tumor cell lines, inducing caspase activation and apoptotic changes. Structurally adriatoxin consists of 10 fused ether rings, 24 stereocenters, 5 methyl groups of which 4 of them are at the angular positions, and a challenging 7-6-8-tricyclic fused ether ring system (i.e., the E,F,G, rings) with the pyranyl ring having methyl groups that are in a 1,3-diaxial orientation. As a result of the interesting biological activity that adriatoxin possesses, its scarcity from the natural source, and its structural complexity, our research group became interested in its synthesis. Although no total synthesis of YTX or its analogues has been reported to date, several approaches to its synthesis have been reported. Described herein are our approaches that harness glycal-epoxide rearrangements for the synthesis of the AB, EF and the IJ ring systems of adriatoxin and the attempted couplings of these subunits.