Abstract
A series of eight 3, 3-disubstituted nitrosoureas (IVa-h) having the nitrosoureido group at the C-6 position of methyl glucopyranoside or methyl 2-acetamido-2-deoxy-glucopyranoside was prepared and tested for antitumor activities. Heating of the 6-O-p-tolylsulfonyl derivatives (I and II) with various alkylamines followed by reaction with 2-chloroethyl isocyanate gave the corresponding ureas (IIIa-h), which were nitrosated with nitrogen tetroxide to give IVa-h in high yields. The nitrosoureas (IVa-h) were significantly less active than the other positional isomers with respect to the nitrosoureido group prepared previously. Compounds IVa-h appear to be activated by a γ hydroxyl group at the C-4 position. The rate of activation, however, proved to be much slower than those of the C-1 or C-3 positional isomers having a β hydroxyl group. The structure-activity relationships of the positional isomers are discussed in the light of this difference in the rate of activation.
