Triazines and related products. Part 25. Methods for the attachment of sugar residues to cytotoxic 1,3,5-triazines

Abstract

The interaction of 2-chloro-4,6-bis(dimethylamino)-1,3,5-triazine (6) with amine nucleophiles gives high yields of substituted 2-amino-1,3,5-triazines. 2-Chloro- and 2-azido-4,6-bis(dimethylamino)-1,3,5-triazines do not afford carbohydrate-linked melamines (2,4,6-triamino-1,3,5-triazines) when treated with glucosamine or methyl 2-amino-2-deoxy-α-D-glucopyranoside.

1,2:5,6-Di-O-isopropylidene-α-D-glucofuranose (13) and the chlorotriazine (6) yielded the 3-O-substituted glucofuranose (14) when heated in N,N-dimethylformamide containing sodium hydride; selective removal of the 5,6- and 1,2-O-isopropylidene groups was achieved in acid media.

The quaternary salt (9) reacted with glucosamine in an alkaline medium to afford an N-triazinylglucosamine (18) and with D- and L-glucose to yield the β-D-glucopyranoside (20) and the enantiomeric β-L-glucoside, respectively.