Enantiospecific synthesis of (-)-alstonerine and (+)-macroline as well as a partial synthesis of (+)-villalstonine

Article abstract of DOI:10.1021/ja00099a021

The enantiospecific synthesis of (-)-alstonerine (5) and (+)-macroline (8), as well as a partial synthesis of the Alstonia bisindole alkaloid villalstonine (2) has been completed. In addition, a more stable macroline equivalent 9 was prepared. The stereochemistry at C(15) and C(16) in 5 and 8 has been successfully installed by a stereoselective Claisen rearrangement followed by stereospecific hydroboration-oxidation of the exocyclic methylene function at C-16. The E ring in alstonerine 5 was constructed by a regioselective cyclization followed by a novel Swern oxidation under modified conditions [(COCl)₂/DMSO/CH₂Cl₂, -78°C to -10°C/1.5 h; Et₃N], whereas the C(20)-C(21) enone system in macroline (8) was generated via a convenient one pot process from the β-diol 45. Condensation of either synthetic (+)-macroline (8) or the macroline equivalent 9 with natural pleiocarpamine 7 in 0.2 N HCl furnished the antiamoebic, antimalarial bisindole alkaloid villalstonine 2. This constitutes the first partial synthesis of any of the Alstonia bisindoles from a synthetically derived indole moiety.