Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 11. Total Syntheses of (−)-Lochneridine and (−)- and Racemic 20-epi-Lochneridine

Enantioselective syntheses of (−)-lochneridine (1) and (−)-epi-lochneridine (2) were obtained by two alternative C-20 diastereoselective syntheses of the respective pentacyclic (3aS,5S,11bR)-methyl 12-oxo-3,5-ethano-2,3,3a,4,5,7-hexahydro-3H-pyrrolo[2,3-d]carbazole-6-carboxylate ((−)-8) and tetracyclic methyl (2S,3aS,5R,11bR))-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(2-(1-butenyl))-1H-pyrrolo[2,3-d]carbazole-6-carboxylate ((−)-12b) precursors from tryptophan derived 2-[(methoxycarbonyl)methyl]-3-[2(S)-(methoxy or benzyloxycarbonyl)-2-(N b-benzyl)aminoethyl]indole (15 or 16). While a modified Grignard reaction of the ketone (−)-8 provided (−)-lochneridine (1), dihydroxylation and cyclization of the olefin (−)-12b gave its C-20 epimer (2).