Synthesis of carbocyclic nucleosides

A synthetic approach to chiral carbocyclic nucleosides of varied ring-sizes using carbon framework of D-glucose

“…Preparation of (1S, 2R, 3S, 4S)-3-(6-dimethylamino-purin-9-yl)-4-hydroxymethylcyclopentane-1, 2-diol (10) and (1S, 2R, 3S, 4S)-4-hydroxymethyl-3-(6-methoxy-purin-9-yl)-cyclopentane-1, 2-diol (11). To the compound 7 (210 mg, 0.76 mmol) dissolved in dry DMF (7 mL) were added p-TSA (215 mg, 1.14 mmol) and freshly distilled CH(OEt) 3 (2mL) and the reaction mixture was stirred for 24 h at room temperature under N 2 . The solvent DMF was evaporated under vacuum, the residue was dissolved in MeOH and the solution was treated with Dowex (OH -) for 5 h. It was filtered and the filtrate was evaporated to give a solid material, which was subjected to flash chromatography using reverse phase material (LiChroprep) as stationary phase.…”

“…After the discovery of the two natural carbocyclic nucleosides (-)-aristeromycin 1 and (-)-neplanocin A 2 possessing antineoplastic activity, considerable attention was paid towards the synthesis of carbocyclic nucleosides with cyclopentane ring [3][4] over the last decade. But little effort has been paid towards the synthesis of such molecules with different ring sizes 5 , particularly with six-and seven-membered rings.…”

Synthesis and antiviral evaluation of 2-amino-1,6-dihydro-6-oxo-9-[4-bis(hydroxymethyl) -2-cyclopenten-1-yl]-9H-purine: an analog of the anti-HIV compound Carbovir

“…1,2 Search for nucleoside analogs which function as nontoxic, selective inhibitors of polymerases and other enzymes for the control of viral diseases and cancer has been the subject of intense research. [3][4][5][6] However, as some of these nucleosides also undergo enzymatic degradations, a number of modifications have been carried out on both the sugar portion and the heterocycle to circumvent or to retard these deactivating processes. Nucleoside analogs that are good substrates for cellular kinases, but are resistant to other host enzymes such as phosphorylases (glycosidic bond cleavage) and deaminases (hydrolytic deamination) are essential for the development of useful therapeutic antiviral agents.…”

Novel Carbocyclic Nucleosides Containing a Cyclobutyl Ring: Adenosine Analogues.

“…[5][6][7][8][9] This wide scope has prompted us to look for similar or improved antiviral properties in analogues of lobucavir with a modified cyclobutane moiety. Although certain limited structure-activity relationships have been inferred for CANs, 10,11) there are as yet no general rules of this kind.…”