9-(2-deoxy-β-D-arabino-hexofuranosyl)adenine | 59837-31-9

• 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: 9-(2-deoxy-β-D-arabino-hexofuranosyl)adenine
• 英文别名: 9-(2-Deoxy-β-D-arabino-hexofuranosyl)adenin；1-(6-amino-purin-9-yl)-β-D-arabino-1,2-dideoxy-hexofuranose；(1R)-1-[(2S,3R,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]ethane-1,2-diol
• CAS: 59837-31-9
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: PMWJXZLFWPNJPC-PULFBKJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N6-苯甲酰基腺嘌呤 在 吡啶 、 4-二甲氨基吡啶 、 三甲基溴硅烷 、 2,2'-azobis(2-propionitrile) 、 三氟化硼乙醚 、 氨 、 三正丁基氢锡 、 sodium methylate 、 四氯化锡 、 一水合肼 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 反应 56.33h， 生成 9-(2-deoxy-β-D-arabino-hexofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine

  摘要：

  1,2-二-O-乙酰基-3,5,6-三-O-苯甲酰-D-葡萄糖呋喃糖与N6-苯甲酰腺嘌呤在四氯化锡催化下缩合，得到核苷I。I的部分去乙酰基化后，进行甲烷磺酰化，得到9-(3,5,6-三-O-苯甲酰-2-O-甲磺酰基-β-D-葡萄糖呋喃糖基)腺嘌呤(III)。1,2,5,6-四-O-乙酰基-3-O-甲磺酰基-D-葡萄糖呋喃糖与N6-苯甲酰腺嘌呤缩合，制备9-(2,5,6-三-O-乙酰基-3-O-甲磺酰基-β-D-葡萄糖呋喃糖基)-N6-苯甲酰腺嘌呤(IV)。III的甲烷基氧化钠甲醇反应和IV的氨甲醇反应形成2',3'-脱水核苷V和VI，分别乙酰化得到9-(5,6-二-O-乙酰基-2,3-脱水-β-D-甘露呋喃糖基)腺嘌呤(VII)和9-(5,6-二-O-乙酰基-2,3-脱水-β-D-异构呋喃糖基)腺嘌呤(VIII)。环氧衍生物VII经溴三甲基硅烷裂解，得到9-(5,6-二-O-乙酰基-2-溴-2-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(Xa)和9-(5,6-二-O-乙酰基-3-溴-3-脱氧-β-D-阿尔托呋喃糖基)腺嘌呤(XIa)的混合物，环氧衍生物VIII类似地裂解，得到9-(5,6-二-O-乙酰基-3-溴-3-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(XIIa)。它们与正丁基锡化合物反应并随后去乙酰基化，得到9-(2-脱氧-β-D-阿拉伯-己呋喃糖基)腺嘌呤(Xc)、9-(3-脱氧-β-D-阿拉伯-己呋喃糖基)腺嘌呤(XIc)和9-(3-脱氧-β-D-核糖-己呋喃糖基)腺嘌呤(XIIc)。通过乙酰化XIIa制备9-(2,5,6-三-O-乙酰基-3-溴-3-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(XIId)，在Cu/Zn偶合物的还原消除和随后的去乙酰基化反应中，得到9-(2,3-二脱氧-β-D-埃里霉素-己-2-烯呋喃糖基)腺嘌呤(XIV)。通过催化氢化溴代衍生物XIId并去乙酰基化，或通过催化氢化二脱氢衍生物XIV，得到9-(2,3-二脱氧-β-D-埃里霉素-己呋喃糖基)腺嘌呤(XVI)。合成的核苷类化合物进行了抗病毒活性测试。

  DOI：

  10.1135/cccc19941408

文献信息

• Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine
  作者：Hubert Hřebabecký、Jan Dočkal、Antonín Holý

  DOI：10.1135/cccc19941408

  日期：——

  Condensation of 1,2-di-O-acetyl-3,5,6-tri-O-benzoyl-D-glucofuranose with N⁶-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I. Partial deacetylation of I, followed by mesylation, gave 9-(3,5,6-tri-O-benzoyl-2-O-methanesulfonyl-β-D-glucofuranosyl)adenine (III). 9-(2,5,6-Tri-O-acetyl-3-O-methanesulfonyl-β-D-glucofuranosyl)-N⁶-benzoyladenine (IV) was prepared by condensation of 1,2,5,6-tetra-O-acetyl-3-O-methanesulfonyl-D-glucofuranose with N⁶-benzoyladenine. Reaction of mesyl derivative III with methanolic sodium methoxide and of mesyl derivative IV with methanolic ammonia led to 2',3'-anhydronucleosides V and VI which were acetylated to give the respective 9-(5,6-di-O-acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine (VII) and 9-(5,6-di-O-acetyl-2,3-anhydro-β-D-allofuranosyl)adenine (VIII). Epoxy derivative VII was cleaved with bromotrimethylsilane, affording a mixture of 9-(5,6-di-O-acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine (Xa) and 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine (XIa), epoxy derivative VIII was cleaved analogously to give 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIIa). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-β-D-arabino-hexofuranosyl)adenine (Xc), 9-(3-deoxy-β-D-arabino-hexofuranosyl)adenine (XIc) and 9-(3-deoxy-β-D-ribo-hexofuranosyl)adenine (XIIc). 9-(2,5,6-Tri-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIId), which was prepared by acetylation of XIIa, on reductive elimination with Cu/Zn couple and subsequent deacetylation gave 9-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)adenine (XIV). 9-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)adenine (XVI) was obtained either by catalytic hydrogenation of bromo derivative XIId followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIV. The synthesized nucleosides were tested for antiviral activity.

  1,2-二-O-乙酰基-3,5,6-三-O-苯甲酰-D-葡萄糖呋喃糖与N6-苯甲酰腺嘌呤在四氯化锡催化下缩合，得到核苷I。I的部分去乙酰基化后，进行甲烷磺酰化，得到9-(3,5,6-三-O-苯甲酰-2-O-甲磺酰基-β-D-葡萄糖呋喃糖基)腺嘌呤(III)。1,2,5,6-四-O-乙酰基-3-O-甲磺酰基-D-葡萄糖呋喃糖与N6-苯甲酰腺嘌呤缩合，制备9-(2,5,6-三-O-乙酰基-3-O-甲磺酰基-β-D-葡萄糖呋喃糖基)-N6-苯甲酰腺嘌呤(IV)。III的甲烷基氧化钠甲醇反应和IV的氨甲醇反应形成2',3'-脱水核苷V和VI，分别乙酰化得到9-(5,6-二-O-乙酰基-2,3-脱水-β-D-甘露呋喃糖基)腺嘌呤(VII)和9-(5,6-二-O-乙酰基-2,3-脱水-β-D-异构呋喃糖基)腺嘌呤(VIII)。环氧衍生物VII经溴三甲基硅烷裂解，得到9-(5,6-二-O-乙酰基-2-溴-2-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(Xa)和9-(5,6-二-O-乙酰基-3-溴-3-脱氧-β-D-阿尔托呋喃糖基)腺嘌呤(XIa)的混合物，环氧衍生物VIII类似地裂解，得到9-(5,6-二-O-乙酰基-3-溴-3-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(XIIa)。它们与正丁基锡化合物反应并随后去乙酰基化，得到9-(2-脱氧-β-D-阿拉伯-己呋喃糖基)腺嘌呤(Xc)、9-(3-脱氧-β-D-阿拉伯-己呋喃糖基)腺嘌呤(XIc)和9-(3-脱氧-β-D-核糖-己呋喃糖基)腺嘌呤(XIIc)。通过乙酰化XIIa制备9-(2,5,6-三-O-乙酰基-3-溴-3-脱氧-β-D-葡萄糖呋喃糖基)腺嘌呤(XIId)，在Cu/Zn偶合物的还原消除和随后的去乙酰基化反应中，得到9-(2,3-二脱氧-β-D-埃里霉素-己-2-烯呋喃糖基)腺嘌呤(XIV)。通过催化氢化溴代衍生物XIId并去乙酰基化，或通过催化氢化二脱氢衍生物XIV，得到9-(2,3-二脱氧-β-D-埃里霉素-己呋喃糖基)腺嘌呤(XVI)。合成的核苷类化合物进行了抗病毒活性测试。