Regiospecific, Enantiospecific Total Synthesis of the Alkoxy-Substituted Indole Bases, 16-epi-Na-Methylgardneral, 11-Methoxyaffinisine, and 11-Methoxymacroline as Well as the Indole Alkaloids Alstophylline and Macralstonine

A regiospecific, enantiospecific approach to the synthesis of ring-A-substituted indole alkaloids was developed via a doubly convergent strategy. The asymmetric Pictet-Spengler reaction and enolate-driven palladium cross-coupling processes were both executed in stereospecific fashion and served as the stereochemical basis of this approach. The synthesis of 16-epi-N(a)-methylgardneral (15), 11-methoxyaffinisine (16), and 11-methoxymacroline (22) has been accomplished in high yield and in enantiospecific fashion. Moreover, the key C-19 ketosarpagine system (borane adducts) 19a,b employed for the construction of 11-methoxymacroline (22) was also transformed into alstophylline 25, which resulted in completion of the total synthesis of the bisindole macralstonine (1). [reaction: see text]