ORGN 702 |
| Gymnodimine, a marine toxin isolated from New Zealand oysters Tiostrea chilensis in 1995 by Yasumoto and coworkers, is known to be responsible for several cases of neurotoxic shellfish poisoning. The potent toxicity, unique structure which includes a spirocyclic imine (proposed pharmacophore) and potentially novel mechanism of action provided impetus to develop a synthetic strategy toward gymnodimine and derivatives. The main synthetic challenges include construction of the azaspirocycle containing a quaternary stereocenter, the labile chiral butenolide, and the 15-membered macrocycle. This presentation will describe the enantioselective construction of the spirocyclic core by a catalytic asymmetric Diels-Alder reaction, fragment coupling, a vinylogous Mukaiyama aldol reaction to directly annulate the butenolide onto a ketone substrate, a reaction with some generality, macrocyclization and final functional group manipulations. Preliminary collaborative studies towards the development of ELISAs to monitor gymnodimine and congeners will also be described.
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Total Synthesis of Complex Molecules
1:00 PM-5:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 132, Oral
Division of Organic Chemistry |
