Total Synthesis of (+)-Nankakurines A and B and (±)-5-epι-Nankakurine A

The first total syntheses of the Lycopochum alkaloids (+)-nankakunne A (2), (+)-nankakurine B (3), and the originally purported structure 1 of nankakunne A were accomplished The syntheses of 2 and 3 feature a demanding intramolecular azomethine imine cycloaddition as the key step for generating the octahydro-3,5-ethanoquinoline moiety and installing the correct relative configuration at the spiropipendine ring juncture The cyclization precursor was prepared from octahydronaphthalene ketone 50, which was assembled from enone (+)-9 and diene 48 by a cationic Diels Alder reaction The Diels Alder reactants were synthesized from 5-hexyn-1-ol (16) and (+)-pulegone (49), respectively The tetracyclic ring system of 1 was generated using an unprecedented nitrogen-terminated aza-Prins cyclization cascade The enantioselective total syntheses of (+)-nankakunne A (2) and (+)nankakunne B (3) establish the relative and absolute configuration of these alkaloids and are sufficiently concise that substantial quantities of 2 and 3 were prepared for biological studies (+)Nankakurine A and (+)-nankakurine B showed no effect on neurite outgrowth in rat hippocampal H-19 cells over a concentration range of 0 3-10 mu M