Total synthesis of (+)-nakadomarin A.
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.
Young
Ian S
IS
Department of Chemistry, University of Western Ontario, London, Ontario N6A 5B7, Canada.
Kerr
Michael A
MA
D000447:Aldehydes / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis*; D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D002243:Carbolines / Q000138:chemical synthesis*; D003500:Cyclization; D003516:Cycloparaffins / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry; D019811:Hydroxylamine / Q000737:chemistry; D008314:Malonates / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008956:Models, Chemical; D010078:Oxazines / Q000737:chemistry; D010084:Oxidation-Reduction; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000470:Alkaloids; D000890:Anti-Infective Agents; D002243:Carbolines; D003516:Cycloparaffins; D003521:Cyclopropanes; D008314:Malonates; D010078:Oxazines; D011759:Pyrrolidines; C476640:nakadomarin A; D019811:Hydroxylamine; D008353:Mannitol; C030797:cyclopropane; C032519:pyrrolidine