[(2R,5S)-5-(6-aminopurin-9-yl)-4,4-difluoro-tetrahydrofuran-2-yl]methanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: [(2R,5S)-5-(6-aminopurin-9-yl)-4,4-difluoro-tetrahydrofuran-2-yl]methanol
• 英文别名: [(2R,5S)-5-(6-aminopurin-9-yl)-4,4-difluorooxolan-2-yl]methanol
• 化学式: C₁₀H₁₁F₂N₅O₂
• 分子量: 271.226
• InChiKey: BLPIFDWBIBAANX-ANLVUFKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl)-2,2-difluoro-3-methylsulfanylthiocarboxyoxy-propionic acid ethyl ester 在 2,6-二甲基吡啶 、 盐酸 、 偶氮二异丁腈 、 偶氮二甲酸二异丙酯 、 氨 、 三正丁基氢锡 、 lithium tri-t-butoxyaluminum hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 70.0h， 生成 [(2R,5S)-5-(6-aminopurin-9-yl)-4,4-difluoro-tetrahydrofuran-2-yl]methanol
  参考文献：
  名称：

  Synthesis of 2,3-dideoxy-2,2-difluoro-l-glycero-pentofuranosyl nucleosides

  摘要：

  Various 2,3-dideoxy-2,2-difluoro-L-glycero-pentofuranosyl nucleosides were synthesized via the key intermediate, 5-O-benzoyl-2,3-dideoxy-2,2-difluoro-L-glycero-pentofuranose (6). 2,3-O-Isopropylidene-L-glyceraldehyde was coupled with ethyl bromodifluoroacetate under Reformatsky conditions to obtain the diastereomeric mixture of ethyl (4S)-3-hydroxy-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-difluoro propionate (1). Treatment of compound 1 with carbon disulfide, sodium hydride and methyl iodide followed by reduction afforded ethyl (4S)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-difluoro propionate (3). Compound 3 was treated with 5% HCl in ethanol, followed by refluxing in benzene under Dean-Stark conditions, to afford the lactone 4. The compound 4 was protected and reduced to afford the key intermediate 6. For the synthesis of pyrimidine derivatives 8-21, compound 6 was converted to the mesylate 7 and condensed with various silyl protected pyrimidine bases. The inosine and adenine derivatives 38-41 were obtained from compound 6 and 6-chloropurine using standard procedures. Compounds 22-35 and 38-41 were evaluated for their antiviral activity against HIV-1, HBV, HSV-1 and HSV-2, and for cellular toxicity. None of the synthesized compounds showed any significant activity or toxicity. Single-crystal X-ray structure of 1-(2,3-dideoxy-2,2-difluoro-beta-L-glycero-pentofuranosyl)-5-iodocytosine (34) suggested a 2'-exo/3'-endo conformation for the carbohydrate moiety. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(97)00275-9

文献信息

• Synthesis of 2,3-dideoxy-2,2-difluoro-l-glycero-pentofuranosyl nucleosides
  作者：Lakshmi P. Kotra、M.Gary Newton、Chung K. Chu

  DOI：10.1016/s0008-6215(97)00275-9

  日期：1998.1

  Various 2,3-dideoxy-2,2-difluoro-L-glycero-pentofuranosyl nucleosides were synthesized via the key intermediate, 5-O-benzoyl-2,3-dideoxy-2,2-difluoro-L-glycero-pentofuranose (6). 2,3-O-Isopropylidene-L-glyceraldehyde was coupled with ethyl bromodifluoroacetate under Reformatsky conditions to obtain the diastereomeric mixture of ethyl (4S)-3-hydroxy-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-difluoro propionate (1). Treatment of compound 1 with carbon disulfide, sodium hydride and methyl iodide followed by reduction afforded ethyl (4S)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-difluoro propionate (3). Compound 3 was treated with 5% HCl in ethanol, followed by refluxing in benzene under Dean-Stark conditions, to afford the lactone 4. The compound 4 was protected and reduced to afford the key intermediate 6. For the synthesis of pyrimidine derivatives 8-21, compound 6 was converted to the mesylate 7 and condensed with various silyl protected pyrimidine bases. The inosine and adenine derivatives 38-41 were obtained from compound 6 and 6-chloropurine using standard procedures. Compounds 22-35 and 38-41 were evaluated for their antiviral activity against HIV-1, HBV, HSV-1 and HSV-2, and for cellular toxicity. None of the synthesized compounds showed any significant activity or toxicity. Single-crystal X-ray structure of 1-(2,3-dideoxy-2,2-difluoro-beta-L-glycero-pentofuranosyl)-5-iodocytosine (34) suggested a 2'-exo/3'-endo conformation for the carbohydrate moiety. (C) 1998 Elsevier Science Ltd. All rights reserved.