Chemical modifications of natural nucleosides

Some chemical modifications of natural nucleosides based on the general organic chemistry have been carried out. Base catalyzed elimination reactions at the 2', 3'-positions of purine and pyrimidine nucleosides proved to be regiospecific. In the pyrimidine series, the resulting 2', 3'-olefins with a leaving group at the C-2' readily formed the corresponding 3'-deoxy-2'-keto-nucleosides, an entirely new class of bioorganic substances. Exploratory experiments aiming at base-sugar cyclization at the 4' -positions of nucleosides led to the N[3],C[4']-cyclization with concomitant decyclization of the base moiety in adenosine series, while in the pyrimidine series the first synthesis of O[2],C[4']-Crcyclonucleosides was achieved. Synthetic studies on the hitherto unexploited nitrogen-bridged cyclonucleosides were extensively conducted. The major topics cover (a) general synthesis of 2,3'-imino and (substituted-imino) pyrimidine nucleosides,(b) regio and stereospecific synthesis of some reversed nucleosides through protected pyrimidine 6,5'-N-cyclonucleosides, (c) general synthesis of purine 8,5'-N-cyclonucleosides, (d) synthesis and chemistry of purine 8,2'- and 8,3'-long-bridged cyclonucleosides, (e) hydrolytic cleavage of the nitrogen bridge in the 2,2'- and 2,3'-(substituted-imino) pyrimidine nucleosides,(f) molecular rearrangements through the fission of the glycosidic bond in the general N-bridged cyclonucleosides, (g) strain-assisted hydrolysis of the nitrogen bridge of a pyrimidine multi-cyclic N-cyclonucleoside and (h) synthesis and chemistry of piperidine sugar uracil nucleosides. The final topic presents the synthesis and chemistry of 3-deoxy-3-nitro-hexopyranosyl nucleosides in both pyrimidine and purine series. The major results are stereoselective Michael addition reactions of various nucleophiles to the 3-nitro-2,3-unsaturated sugar nucleosides in both cases.