Divergent total synthesis of the tricyclic marine alkaloids lepadiformine, fasicularin, and isomers of polycitorols by reagent-controlled diastereoselective reductive amination

We describe a flexible and divergent route to the pyrrolo-/pyrido[1,2-j]quinoline frameworks of tricyclic marine alkaloids via a common intermediate formed by the ester-enolate Claisen rearrangement of a cyclic amino acid allylic ester. We have synthesized the proposed structure of polyci-torols and demonstrated that the structure of these alkaloids requires revision. In addition to asymmetric formal syntheses, stereoselective and concise total syntheses of (-)-lepadi-formine and (-)-fasicularin were also accomplished from simple, commercially available starting materials in a completely substrate-controlled manner. The key step in these total syntheses was the reagent-dependent stereoselective reductive amination of the common intermediate to yield either indolizidines 55 a or 55 b. Aziridinium-mediated carbon homologation of the hindered C-10 group to the homoallylic group facilitated the synthesis.