3-bromopyrazolo[3,4-d]pyrimidine 2 `-deoxy-2 `-fluoro-beta-D-arabinonucleosides: Modified DNA constituents with an unusually rigid sugar N-conformation

Autor(en): He, JL
Mikhailopulo, I
Seela, F
Stichwörter: 2'-DEOXYGUANOSINE; 2'-DEOXYRIBONUCLEOSIDES; 7-HALOGENATED 8-AZA-7-DEAZA-2'-DEOXYGUANOSINES; ALLOPURINOL; BIOLOGICAL-ACTIVITY; Chemistry; Chemistry, Organic; DERIVATIVES; NMR SPECTROSCOPY; NUCLEOSIDES; PHASE-TRANSFER GLYCOSYLATION; STABILITY
Erscheinungsdatum: 2003
Herausgeber: AMER CHEMICAL SOC
Journal: JOURNAL OF ORGANIC CHEMISTRY
Volumen: 68
Ausgabe: 14
Startseite: 5519
Seitenende: 5524
Zusammenfassung: 
The nucleobase anion glycosylation of 3-bromo-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine (6) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (5) furnished the protected N-1-beta-D-nucleosides 7 (60%) and 8 (ca. 2%) along with the N-2-beta-D-regioisomer 9 (9%). Debenzoylation of compounds 7 and 9 yielded the nucleosides 10 (81%) and 11 (76%). Compound 10 was transformed to the 2'-deoxyguanosine derivative 1 [6-amino-3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)1H-pyrazo lo[3,4-d]pyrimidin-4-one] (85% yield) and the purine-2,6-diamine analogue 2 [3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1H-pyrazolo[3, 4-d]pyrimidin-4, 6-diamine] (78%). Both nucleosides form more than 98% N-conformer population (P-N ca. 358degrees and psi(m) ca. 37) in aqueous solution. Single-crystal X-ray analysis of I showed that the sugar moiety displays also the N-conformation [P = 347.3degrees and psi(m) = 34.4degrees] in the solid state. The remarkable rigid N-conformation of the pyrazolo[3,4-d]pyrimidine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 1 and 2 observed in solution is different from that of the parent purine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 3 and 4, which are in equilibrium showing almost equal distribution of the N/S-conformers.
ISSN: 00223263
DOI: 10.1021/jo030051p

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