Syntheses of purine-like C-nucleosides and their precursors

The work described in this thesis is part of an ongoing program at The American University. Its goal is the synthesis and screening of potential antiviral and antitumor agents. The work started with the synthesis of a versatile carbohydrate synthon, ethyl 2,5-anydro-6-O-benzoyl- sc D-allono-dithioate, which was utilized for the synthesis of seven purine-like C-nucleosides, presently undergoing biological screening. The synthon was first coupled with o-aminophenol, 2,3-diaminopyridine, and 5,6-diamino-1,3-dimethyluracil to yield 2-D-ribofuranosylbenzoxazole, 2-($\beta$- sc D-ribofuranosyl)-1H-imidazo (4,5-b) pyridine and 8-($\beta$- sc D-ribofuranosyl)-1,3-dimethylxanthine, respectively. Comparison of the yields obtained by this method and by using other synthons revealed that the yields of nucleosides obtained by using the newly prepared synthon were invariably superior. The synthon was accordingly used exclusively to prepare the remaining nucleosides. The latter are nitrogen-bridged C-nucleosides, which were formed by coupling ethyl 2,5-anhydro-6-O-benzoyl- sc D-allonodithiolate with 2-aminomethyl-pyridine, 2-hydrazinopyrazine, and three hydrazinopyrimidines. The first two bases afforded as expected 3-$\beta$- sc D-ribofuranosylimidazo (1,5-a) pyridine and 3-$\beta$- sc D-ribofuranosyl-1,2,4-triazolo (4,3-a) pyrazine, respectively. However coupling the synthon with hydrazinopyrimidines was complicated by the fact that some of the resulting C-nucleosides possessed purine-like bases (such as, 1,2,4-triazolo (4,3-a) pyrimidines) which are known to undergo rearrangement. This is why when ethyl 2,5-anhydro-6-O-benzoyl- sc D-allonodithioate was coupled with 2-hydrazinopyrimidine it afforded 2-(5$\sp\prime$-O-benzoyl-$\beta$- sc D-ribo-furanosyl)-1,2,4-triazolo (1,5-a) pyrimidine instead of the expected 3-(5$\sp\prime$-O-benzoyl-$\beta$- sc D-ribofuranosyl)-1,2,4-triazolo (4,3-a) pyrimidine. On the other hand, 2-hydrazino-4-hydroxy-6-methylpyrimidine and 5-chloro-4-hydrazino-pyrimidine afforded the desired unrearranged C-nucleosides, namely 3-$\beta$- sc D-ribofuranosyl-5-methyl-1,2,4-triazolo (4,3-a) -7(8H)-pyrimidone and 3-(5$\sp\prime$-O-benzoyl-$\beta$- sc D-ribofuranosyl)-8-chloro-1,2,4-triazolo (4,3-c) -pyrimidine, respectively. The C-nucleosides prepared are presently undergoing biological screening.