Web Release Date: January 11,
Total Synthesis of (+)-Nakadomarin A
Contribution from the Department of Chemistry, University of Western Ontario, London, Ontario N6A 5B7, Canada
Received November 10, 2006
Abstract:
The total synthesis of (+)-nakadomarin A is described. A three-component cycloaddition of a hydroxylamine, aldehyde, and cyclopropane to form a highly functionalized tetrahydro-1,2-oxazine serves as the foundation for this synthesis. The resulting oxazine is formed as a single diastereomer with the absolute configuration being dictated by the chirality of the cyclopropane. Other key steps include: desymmetrization of a malonate by reduction, Heck cyclization and pyrrolidine formation, and ring-closing metathesis to form both cycloalkenes. Overall, the synthesis required 23 linear steps from the cyclopropane, which in turn is available (six steps) in optically pure form from commercially available D-mannitol.
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