Pyrazolo[3,4-d]pyrimidine ribonucleosides related to 2-aminoadenosine and isoguanosine: synthesis, deamination and tautomerism

Autor(en): Seela, Frank
Xu, Kuiying
Stichwörter: ALLOPURINOL RIBONUCLEOSIDE; BASE-PAIRING PROPERTIES; BIOLOGICAL-ACTIVITY; Chemistry; Chemistry, Organic; DERIVATIVES; DNA; GLYCOSYLATION; LEISHMANIA-BRAZILIENSIS; MISMATCH DISCRIMINATION; NUCLEOSIDES; OLIGONUCLEOTIDE DUPLEXES
Erscheinungsdatum: 2007
Herausgeber: ROYAL SOC CHEMISTRY
Journal: ORGANIC & BIOMOLECULAR CHEMISTRY
Volumen: 5
Ausgabe: 18
Startseite: 3034
Seitenende: 3045
Zusammenfassung: 
The syntheses and properties of 8-aza-7-deazapurine(pyrazolo[3,4-d] pyrimidine)ribonucleosides related to 2-aminoadenosine and isoguanosine are described. Glycosylation of 8-aza-7-deazapurine-2,6-diamine 5 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose ( 12) in the presence of BF3 center dot Et2O as a catalyst gave the N-8 isomer 14 (73%) with a trace amount of the N-9 isomer 13a (4.8%). Under the same reaction conditions, the 7-halogenated 8-aza-7-deazapurine-2,6-diamines 6-8 afforded the thermodynamically more stable N-9 nucleosides 13b-d as the only products (53-70%). Thus, a halogen in position 7 shifts the glycosylation from N-8 to N9. The 8-aza-7-deazapurine-4,6-diamine ribonucleosides 1a-d were converted to the isoguanosine derivatives 3a-d by diazotization of the 2-amino group. Although compounds 1a, b do not contain a nitrogen at position 7 (the enzyme binding site), they were deaminated by adenosine deaminase; however, their deamination occurred with a much slower velocity than that of the related purines. The pK(a) values indicate that the 7-non-functionalized nucleosides 1a (pK(a) 5.8) and 15 (pK(a) 6.4) are possibly protonated in neutral conditions when incorporated into RNA. The nucleosides 3a-d exist predominantly in the keto ( lactam) form with K-TAUT (keto/enol) values of 400-1200 compared to 10(3)-10(4) for pyrrolo[2,3-d]pyrimidine isoguanosine derivatives 4a-c and 10 for isoguanosine itself, which will reduce RNA mispairing with U.
ISSN: 14770520
DOI: 10.1039/b708736e

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