ENANTIOSPECIFIC SYNTHESIS OF (-)-ALSTONERINE AND (-MACROLINE AS WELL AS A PARTIAL SYNTHESIS OF (+)-VILLALSTONINE())

The enantiospecific synthesis of (-)-alstonerine (5) and (+)-macroline (8), as well as a partial synthesis of the Alstonia bisindole alkaloi d villalstonine (2) has been completed. In addition, a more stable mac roline equivalent 9 was prepared. The stereochemistry at C(15) and C(1 6) in 5 and 8 has been successfully installed by a stereoselective Cla isen 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 degrees C to -10 degrees C/1.5 h; Et(3)N], whereas the C(20)-C(21) en one system in macroline (8) was generated via a convenient one pot pro cess from the beta-diol 45. Condensation of either synthetic (+)-macro line (8) or the macroline equivalent 9 with natural pleiocarpamine 7 i n 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.