Synthetic studies on indoles and related compounds. Part 46. First total syntheses of 4,8-dioxygenated beta-carboline alkaloids

Total syntheses of naturally occurring 4,8-dioxygenated beta-carboline alka loids 2a, 2d, 2g, and 2h are described. The synthetic route involves two me thodologies that we developed; (i) an improved Fischer indolization for the synthesis of a 7-oxygenated indole using a tosyl group for protection of t he phenolic group, (ii) construction of a 4-methoxy-beta-carboline skeleton by the C-3-selective cyclization of the C-2-substituent of the indole nucl eus. The phenolic O-tosyl group of the beta-carboline skeleton was successf ully cleaved to the phenol by Na-anthracenide, and this phenol was methylat ed with TMSCH2N2.