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

Abstract

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-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.

Silver Ions in Non‐canonical DNA Base Pairs: Metal‐Mediated Mismatch Stabilization of 2′‐Deoxyadenosine and 7‐Deazapurine Derivatives with 2′‐Deoxycytidine and 2′‐Deoxyguanosine

“…[16] Stable, protonated noncanonical base pairs are assumed to promote the replacement of H + with Ag I ions. [17,18] The 7-deazapurine system changest he pK a of the "adenine" base and enforces base pairing to the Watson-Crick face of the nucleoside, whereas the 7-iodo or 7-cyclopropylr esiduesa re expected to alter the steric demand of silver-mediated base pairs within the major groove of the DNA double helix. Moreover,t he high stability of the non-canonical base pairs used in this study is expected to limit as tabilityi ncrease that is promoted by the incorporation of silver ions compared with the silver-free dCÀdC or dTÀdT mismatched base pairs.…”

“…This manuscript reports on 12‐mer duplexes that contain non‐canonical dA−dC, dA−dG, dA*−dC, and dA*−dG base pairs and their binding of silver ions. The term dA* is used in this study to denote 7‐deaza‐2′‐deoxyadenosine ( C7 A d , 2 a ), 7‐cyclopropyl‐7‐deaza‐2′‐deoxyadenosine ( 7CP A d , 2 b ), and 7‐deaza‐7‐iodo‐2′‐deoxyadenosine ( 7I A d , 2 c ) (Figure c) . The 7‐deazapurine system changes the p K a of the “adenine” base and enforces base pairing to the Watson–Crick face of the nucleoside, whereas the 7‐iodo or 7‐cyclopropyl residues are expected to alter the steric demand of silver‐mediated base pairs within the major groove of the DNA double helix.…”

Synthesis of 8-(1,2,3-triazol-1-yl)-7-deazapurine nucleosides by azide–alkyne click reactions and direct C H bond functionalization

“…10–12 In recent years 7-deazapurine nucleosides have been explored as substrates for 1,4-regioselective copper-catalyzed azide/alkyne cycloaddition (CuAAC), which resulted in developing fluorogenic DNA probes. 13–16 These studies have mainly concentrated on the application of 7-alkynyl derivatives of 7-deazapurines and 7-deazanucleosides for the preparation of the fluorescent 1,2,3-triazol-4-yl probes.…”

Synthesis of Purine and 7‐Deazapurine Nucleoside Analogues of 6‐N‐(4‐Nitrobenzyl)adenosine; Inhibition of Nucleoside Transport and Proliferation of Cancer Cells

“…[1] A sizeable number of active nucleoside compounds with such a pyrrolo[2,3- d ]pyrimidine base has been prepared by chemical modifications of the parent antibiotics as well as by coupling base derivatives with protected sugars. [2] Noteworthy examples of such molecules include: (a) 5-iodotubercidin, [3] an up-field activator of the p53 pathway; (b) sangivamycin analogues such as 6-hydrazinosangivamycin [4] and xylocidine, [5] in vitro down-field inhibitors of PKC and CDK in cancer cell lines; (c) a methyl-substituted tubercidin, [6] which acts against the replication of polio and dengue viruses; (d) the anti-HSV agent xylotubercidin; [7] (e) substituted toyocamycin analogues [8] and 2′-β- C -methyl derivative of toyocamycin, [9] sangivamycin, [9] and tubercidin [10] that have activity against HCV; (f) 2′-deoxy-2′-fluoroarabinotubercidin [11] and 2-amino-2′-deoxy-2′-fluoroarabinotubercidin, [12] which exhibit antiviral activity; (g) 4 N ,5-diaryltubercidin derivatives, which act as adenosine kinase inhibitors; [2 l , 13] and (h) tubercidin derivatives such as 4-(het)aryl, [14] 5-(het)aryl [15] and some 4-substituted-5-(het)aryl [16] compounds with nanomolar cytostatic activity against several cancer cell lines.…”