Synthesis of the 2,3,4-trisubstituted indole fragments of nosiheptide and glycothiohexide

Two routes to the protected 4-hydroxymethyl-3-methylindole-2-carboxylate fragment 17 of the thiopeptide antibiotic nosiheptide are described starting from methyl 4-methylindole-2-carboxylate 11, itself prepared in two steps, or from 3-amino-4-chlorobenzoic acid 26. The first route can be adapted to the synthesis of a fragment of the related antibiotic glycothiohexide-alpha, the 3,4-bis(hydroxymethyl) indole-2-carboxylate in which the two hydroxymethyl groups are differentiated as in indole 19 or the lactone 20.