Search for a simpler synthetic model system for intramolecular 1,3-dipolar cycloaddition to the 5,6-double bond of a pyrimidine nucleoside

Abstract

In search for a simpler model system for the study of intramolecular thermal reactions between the base and 5'-functionalized sugar moiety in nucleosides, 1-(3-azidopropyl)uracil ( 2), 1-(4-azidobutyl) pyrimidines ( 12 and 13) and 1-(5-azidopentyl)-uracil ( 14) was synthesized through the corresponding ω-benzoyloxy-( 6, 7 and 8) and ω-hydroxyalkyl-pyrimidines ( 9, 10 and 11). Heating 2 gave 1,N 6-trimethylene-6-aminouracil ( 4), while heating 12 and 13 gave N 1-C 6 cleaved addition products. 15 and 16, respectively. 15 was regiospecifically transformed to 1,2,3-triazole derivatives, 17, 18 and 19. Heating 1-(4-azidobutyl)-5-bromouracil ( 20) yielded 3,9-tetramethylene-8-azaxanthine ( 22). 9 with NBA gave 1,0 6-tetramethylene-5-bromo-6-hydroxy-5,6-dihydrouracil ( 24) and the 5-brominated analog of 9 ( 25). The 4-functionalized butyl side chain proved to serve as a substitute for the 5'-functionalized sugar moiety in pyrimidine ribonucleosides.