Synthesis of 2,3-Didehydro-2,3-dideoxynucleosides via Nucleoside Route.

Abstract

2',3'-Didehydro-and 2',3'-dideoxynucleosides are both potent antiviral agents. In particular, they are Nucleoside Reverse Transcriptase Inhibitors and hence active against HIV, the ethiological agent of AIDS. They are also intermediates for the synthesis of antiviral 2',3'-dideoxynucleosides. Various aspects of synthetic routes to 2',3'-unsaturated nucleosides are reviewed with examples being chosen from work published between 1966 and 2003.

Stereospecific Benzyne‐Induced Olefination from β‐Amino Alcohols and Its Application to the Total Synthesis of (−)‐1‐Deoxy‐D‐fructose

“…Herein, we contribute a new method to form the C=C bond that is complementary to existing methods. Some of the prominent methods include the coupling of aldehydes with organic phosphonium halides in the Wittig reaction, [2] the coupling of two aldehydes in the McMurry reaction, [3] the decomposition of cyclic thionocarbonates in the CoreyWinter reaction, [4,5] the decomposition of cyclic 2-alkoxy-1,3-dioxolanes in the Eastwood olefination, [5] the deoxygenation of epoxides, [1] and so forth. Alternatively, the C=C bond can be generated by 1,2-elimination reactions of substrates containing various functional groups.…”

“…Alternatively, the C=C bond can be generated by 1,2-elimination reactions of substrates containing various functional groups. These substrates could be b-silyl alcohols in the Peterson olefination, [6] bisdithiocarbonates in the Barton deoxygenation, [5] 1,2-dihalides with zinc in DMSO, [1] or 1,2-diols and their derivatives under reductive conditions. [1] However, disadvantages and limitations exist in some of these methods, [1,3,5] such as demands on toxic reagents, incompatibility of other reducible functional groups with the applied strong reducing reagents, the lack of stereospecific control when forming the C=C bond, and so forth.…”

“…[4,5] Although the possible stereogenic carbon centers attached to the hydroxyl groups are destroyed after the double bond is formed, often the final products (e.g., trichodermamides and valienamine) could still possess optical activity. [20] The same logic is applicable to our new olefination method by the use of b-amino alcohols as starting materials to produce asymmetric products.…”

Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

“…Nucleoside and nucleotide modifications resulted in an increased interest in the regio- and stereoselective synthesis of nucleosides [10,11]. Moreover, modified nucleosides and nucleotides with a restricted conformation have been used to reach a particular conformation of a rotamer to study the affinity of a biomacromolecule for its natural ligand as well as the molecular recognition in an oligonucleotide chain (RNA/DNA) [12,13,14,15]. Similar studies of anti-sense and anti-gene oligonucleotides (ONs) as potential and selective inhibitors of gene expression [16,17,18,19] and their use as anti-tumor or anti-viral agents [20,21,22,23] have also influenced the developments in the field of nucleic acid-based drugs.…”

Synthesis of Azanucleosides through Regioselective Ring-Opening of Epoxides Catalyzed by Sulphated Zirconia under Microwave and Solvent-Free Conditions

“…The modification of nucleosides has been recognized as an important research area to improve their antiviral activities [15,16,17,18,19,20,21,22,23,24,25,26]. Each biologically active nucleoside is constituted by the heterocyclic base moiety, a furanose ring and a hydroxymethyl group (Figure 1a), which participate in the recognition process to achieve biological activity via the phosphorylation of hydroxymethyl group [27].…”