Development of an enantioselective route toward the Lycopodium alkaloids: total synthesis of lycopodine.
Synthesis of a C(15)-desmethyl tricycle core of lycopodine has been accomplished. Key steps in the synthetic sequence include organocatalytic, intramolecular Michael addition of a keto sulfone and a tandem 1,3-sulfonyl shift/Mannich cyclization to construct the tricyclic core ring system. Synthetic work toward this natural product family led to the development of N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide, an organocatalyst which facilitates enantioselective, intramolecular Michael additions. A detailed mechanistic discussion is provided for both the intramolecular Michael addition and the sulfone rearrangement. Finally, the application of these discoveries to the enantioselective total synthesis of alkaloid lycopodine is described.
Yang
Hua
H
Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, Oregon 97331, USA.
Carter
Rich G
RG
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D032502:Lycopodium / Q000737:chemistry*; D011807:Quinolizines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D011807:Quinolizines; C016542:lycopodine