He Junlin, Mikhailopulo Igor, Seela Frank
Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastrasse 7, D-49069 Osnabrück, Germany.
J Org Chem. 2003 Jul 11;68(14):5519-24. doi: 10.1021/jo030051p.
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-pyrazolo[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. 358 degrees and psi(m) ca. 37 degrees ) in aqueous solution. Single-crystal X-ray analysis of 1 showed that the sugar moiety displays also the N-conformation [P = 347.3 degrees and psi(m) = 34.4 degrees ] 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.
3-溴-4-异丙氧基-1H-吡唑并[3,4-d]嘧啶-6-胺（6）与3,5-二-O-苯甲酰基-2-脱氧-2-氟-α-D-阿拉伯呋喃糖基溴（5）的核碱基阴离子糖基化反应得到了受保护的N(1)-β-D-核苷7（60%）和8（约2%）以及N(2)-β-D-区域异构体9（9%）。化合物7和9的脱苯甲酰基反应得到了核苷10（81%）和11（76%）。化合物10被转化为2'-脱氧鸟苷衍生物1 [6-氨基-3-溴-1-(2-脱氧-2-氟-β-D-阿拉伯呋喃糖基)-1H-吡唑并[3,4-d]嘧啶-4-酮]（产率85%）和嘌呤-2,6-二胺类似物2 [3-溴-1-(2-脱氧-2-氟-β-D-阿拉伯呋喃糖基)-1H-吡唑并[3,4-d]嘧啶-4,6-二胺]（78%）。两种核苷在水溶液中形成的N-构象体群体均超过98%（P(N)约358°，ψ(m)约37°）。1的单晶X射线分析表明，糖部分在固态下也呈现N-构象[P = 347.3°，ψ(m) = 34.4°]。在溶液中观察到的吡唑并[3,4-d]嘧啶2'-脱氧-2'-氟-β-D-阿拉伯核苷1和2显著的刚性N-构象不同于母体嘌呤2'-脱氧-2'-氟-β-D-阿拉伯核苷3和4，它们处于平衡状态，N/S-构象体的分布几乎相等。
