ALKYLATING NUCLEOSIDES .2. SYNTHESIS AND CYTOSTATIC ACTIVITY OF BROMOMETHYLPYRAZOLE AND PYRAZOLE NITROGEN-MUSTARD NUCLEOSIDES

Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucleosides 5 and 7, respectively. In some cases, the positional isomers 6 and 8 were also obtained. Treatment of 5 and 7 with methanolic ammonia gave the deprotected 3-(aminomethyl)pyrazole-5-carboxamide nucleosides 9. Reaction of 3-5 and 7 with bis(2-chloroethyl)amine led to the corresponding pyrazole nitrogen mustards 10-13. All the bromomethylpyrazole nucleosides described showed significant cytostatic activity against HeLa cell cultures. © 1979, American Chemical Society. All rights reserved.