3',5'-Di-O-benzyl-N¹-benzylinosine | 136852-26-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3',5'-Di-O-benzyl-N¹-benzylinosine
• 英文别名: 1-benzyl-9-[(2R,3R,4S,5R)-3-hydroxy-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-2-yl]purin-6-one
• CAS: 136852-26-1
• 化学式: C₃₁H₃₀N₄O₅
• 分子量: 538.603
• InChiKey: KBRZWTSMRORZNN-QWOIFIOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3',5'-Di-O-benzyl-N¹-benzylinosine 在 吡啶 、 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 以41%的产率得到9-(3',5'-Di-O-benzyl-β-D-erythro-pent-2-enofuranosyl)-1-benzylhypoxanthine
  参考文献：
  名称：

  A synthesis of 9-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)adenine and -hypoxanthine. An effect of C3'-endo to C2'-endo conformational shift on the reaction course of 2'-hydroxyl group with DAST

  摘要：

  O3',O5',N6-Tritrityladenosine (6), 3',5'-di-O-trityl-N1-benzylinosine (15), and 3',5'-di-O-tritylinosine (18) were prepared and subjected to nucleophilic reaction with DAST. Thus, 6 afforded 2'-beta-fluorine-substituted nucleoside 11 along with the isomeric 2-deoxy-2-(N-trityladenin-3-yl)-3,5-di-O-trityl-alpha-D-arabinofuranosyl fluoride (12). Nucleoside 15, under the same treatment with DAST, gave the desired 2'-fluoroarabino derivative 16 exclusively in high yield. Although 18 was converted into the 2'-beta-fluoro product 19 under the similar conditions, the yield was low. A plausible mechanism of formation of 12 is discussed. Deprotection of 11 and 16 afforded the desired 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (1) and -hypoxanthine (2), respectively, in high yield. The conformational influence of sugar protecting groups on the rate of nucleophilic substitution against elimination is discussed. Treatment of O3',O5',N1-benzylinosine (20) with DAST afforded only the elimination products 9-(3',5'-di-O-benzyl-beta-D-erythro-pent-2-enofuranosyl)-1-benzylhypoxanthine (22) and 3-(benzyloxy)-2-[(benzyloxy)methyl]furan (23). On the other hand, 9-(3,5-di-O-trityl-beta-D-arabinofuranosyl)adenine (26) (prepared from 6 by triflyation followed by NaOAc treatment and deacetylation) afforded a mixture from which 2'-deoxy-2'-fluoroadenosine (27) and 9-(2-deoxy-3,5-di-O-trityl-D-erythro-pent-1-enofuranosyl)-N6-trityladenine (28) were isolated in 60 and 30% yield, respectively. O2',O5',N6-Tritrityladenosine (7) was selectively detritylated with HCO2H/Et2O to give O2',N6-ditrityladenosine (30), which, upon treatment with benzyl chloride/KOH, afforded 3',5'-di-O-benzyl-O2',N6-ditrityladenosine (31). 9-(3,5-Di-O-benzyl-beta-D-arabinofuranosyl)adenine (35) was prepared from 31 by further detritylation with CF3CO2H/CHCl3 and triflyation followed by NaOAc treatment and deacetylation of the product. Treatment of 35 with DAST followed by hydrogenolytic debenzylation afforded 2'-deoxy-2'-fluoroadenosine (3) in high yield. The three-step synthesis described herein, albeit about 10% overall yield, is far superior to the currently available multistep procedures which give the desired 2'-fluoroarabinosylpurines in much less overall yields.

  DOI：

  10.1021/jo00028a030