Yoshihisa Arai

A New Class of Nitrosoureas. VI. Synthesis and Antitumor Activity of 3-Substituted-1-(2-chloroethyl)-3-(methyl-α-D-glucopyranosid-2-yl)-1-nitrosoureas

A series of five 3, 3-disubstituted nitrosoureas having the nitrosoureido group at the C-3 position of methyl glucoside were prepared and tested for antitumor activities. Heating of methyl 2, 3-anhydro-α-D-allopyranoside (I) with various alkylamines followed by reaction with 2-chloroethyl isocyanate gave two regioisomers (II and III). The major product (II) and the minor product (III) were determined to be the ureido derivatives of methyl glucoside and methyl altroside, respectively. Nitrosation of II with dinitrogen tetroxide gave 3-substituted 1-(2-chloroethyl)-3-(methyl α-D-glucopyranosid-3-yl)-1-nitrosoureas (VI) in good yields. All the nitrosoureas obtained were remarkably active against leukemia L-1210 and Ehrlich ascites carcinoma. The structure-activity relationships of positional isomers with respect to the nitrosoureido group are discussed.