7-Deazapurine (Pyrrolo[2,3-d]pyrimidine) 2-Deoxyribonucleosides: Syntheses and Transformations

Frank Seela, Simone Budow, Xiaohua Peng
2012 Current organic chemistry  
This review reports on the synthesis of 7-deazapurine (pyrrolo[2,3-d]pyrimidine) 2'-deoxyribonucleosides, including -D-and -L-enantiomers, fluoro derivatives, and 2',3'-dideoxyribonucleosides. It covers the various aspects of convergent nucleoside synthesis. Stereochemically defined -D and -L 2'-deoxyribonucleosides as well as sugar derivatives were prepared by nucleobase anion glycosylation. This glycosylation reaction is regioselective for the pyrrole nitrogen and stereoselective for
more » ... ective for -nucleoside formation. Common glycosylation protocols lead to 7-deazapurine 2'-deoxyribonucleosides with unusual glycosylation sites. 7-Deazapurine 2',3'dideoxyribonucleosides were also obtained from 2'-deoxy-or 3'-deoxyribonucleosides by Barton-McCombie deoxygenation, by elimination of sugar hydroxyl groups or by anion glycosylation. Another aspect of the review is the functionalization of pyrrolo[2,3-d]pyrimidine nucleosides. A broad range of reporter groups were introduced by the Sonogashira cross coupling or the copper(I)-catalyzed Huisgen-Meldal-Sharpless "click" reaction. The application of 7-deazapurine nucleosides as antiviral or anticancer agents, and the use of 7deazapurine nucleoside triphosphates in the Sanger dideoxy DNA-sequencing are also reported. R Fig (3). 7-Deazapurine (Pyrrolo[2,3-d]pyrimidine) 2'-Deoxyribonucleosides Current Organic Chemistry, 2012, Vol. 16, No. 2 163 role nitrogen directs the glycosylation towards the pyrimidine moiety or takes place on the more nucleophilic pyrrole carbons. This problem was overcome by generating the pyrrolyl anion which is highly reactive and allows glycosylation at ambient temperature. Consequently, the anomerically defined sugar halides employed in the glycosylation do not isomerise. The generation of the pyrrolyl anion was originally applied to ribonucleoside synthesis [35, 36] . Later, it was used by our laboratory to synthesize 7-deazapurine arabinonucleosides [37] , and presently we employ this method in the synthesis of 7-deazapurine 2'-deoxyribonucleosides. The stereoselective nucleobase anion glycosylation [33, 34, 38] , which is now the most widely used protocol for the synthesis of purine or purine related 2'-deoxyribonucleosides, utilizes sugar halides with defined configuration at the anomeric center. As several sugar halides (halogenoses) are accessible as pure -D-or -Lanomers, the synthesis of 7-deazapurine 2'-deoxyribonucleosides proceeds under stereochemical control with the exclusive formation of -D-2'-deoxyribonucleosides or -L-2'-deoxyribonucleosides. A large number of 7-deazapurine nucleosides have been synthesized under these conditions [30, 38, 39] . Many of them show antiviral or anticancer activity and several have been incorporated into oligonucleotides [12] . SYNTHESIS OF 7-DEAZAPURINE -PYRROLO[2,3d]PYRIMIDINE -2'-DEOXYRIBONUCLEOSIDES
doi:10.2174/138527212798993086 fatcat:wxxa56idd5fyxo7azttlszyuay