Versatile synthesis of 6-substituted 8-deazapteridine-2,4-diamines. Formal total synthesis of 8,10-dideazaminopterin

A new synthesis of 4-amino-4-deoxy-8,10-dideazapteroic acid (11d) and 6-substituted and 5,6-anellated 8-deazapteridine-2,4-diamines, 10a, 10d, 25, is described. Starting from keteneaminals 1 or 12 and enaminones 4 or beta-aminoketone 17 the title compounds can be prepared via functional group transformation of 2-amino-3-nitropyridines 5 or nicotinate 13a yielding 3-amino-alpha-picolinonitriles 9 which are cyclocondensed with guanidine.