9-(2,3-anhydro-4-C-hydroxymethyl-α-L-lyxofuranosyl)adenine | 160533-35-7

• 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-(2,3-anhydro-4-C-hydroxymethyl-α-L-lyxofuranosyl)adenine
• 英文别名: 9-(4-hydroxymethyl-2,3-anhydro-β-D-ribofuranosyl)adenine；9-(2,3-anhydro-4-hydroxymethyl-β-D-ribofuranosyl)adenine；[(1S,4R,5R)-4-(6-aminopurin-9-yl)-2-(hydroxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]methanol
• CAS: 160533-35-7
• 化学式: C₁₁H₁₃N₅O₄
• 分子量: 279.255
• InChiKey: VVJAHXIDVLBFQT-MATHAZKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-(2,3-anhydro-4-C-hydroxymethyl-α-L-lyxofuranosyl)adenine 在 4-二甲氨基吡啶 、 三甲基溴硅烷 、 2,2'-azobis(2-propionitrile) 、 三氟化硼乙醚 、 三正丁基氢锡 作用下， 以 乙腈 为溶剂， 反应 3.33h， 生成 9-(4-C-acetoxymethyl-5-O-acetyl-2-deoxy-α-L-threo-pentofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine

  摘要：

  1,2-二-O-乙酰基-3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-L-阿拉伯呋喃糖与N6-苯甲酰腺嘌呤在四氯化锡催化下缩合，得到核苷I，经过部分去乙酰化和随后的甲磺酰化，转化为9-(3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-2-O-甲磺酰基-α-L-阿拉伯呋喃糖基)腺嘌呤(III)。1,2,5-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-L-阿拉伯糖与N6-苯甲酰腺嘌呤缩合，得到9-(2,5,6-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-α-L-阿拉伯呋喃糖基)-N6-苯甲酰腺嘌呤(V)。将甲烷醇钠甲醇溶液与甲磺酰衍生物III和V反应，得到2',3'-脱水核苷VIa和VIIa，它们被乙酰化，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-核糖呋喃基)腺嘌呤(VIb)和9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-吕克索呋喃基)腺嘌呤(VIIb)。环氧衍生物VIb被溴三甲基硅烷裂解成9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)腺嘌呤(VIIIa)；用环氧衍生物VIIb进行相同的反应，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-吕克索呋喃糖基)(IXa)和9-(5-O-乙酰基-4-C-乙酰氧甲基-3-溴-3-脱氧-α-L-阿拉伯呋喃糖基)(Xa)的混合物。它们通过三丁基锡脱卤素化和随后的去乙酰化，得到9-(2-脱氧-4-C-羟甲基-α-L-erythro-戊糖基)腺嘌呤(VIIIc)、9-(2-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(IXc)和9-(3-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(Xc)。通过乙酰化VIIIa得到9-(2,5-二-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)(VIIId)，经过Cu/Zn偶联还原消除和随后的去乙酰化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pent-2-enofuranosyl)腺嘌呤(XIb)。通过VIIId的催化氢化，随后去乙酰化，或者通过XIb的双脱氢衍生物的催化氢化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pentofuranosyl)腺嘌呤(XIIb)。合成的核苷类化合物被用于抗病毒活性测试。

  DOI：

  10.1135/cccc19941654
• 作为产物：
  描述：

  N6-苯甲酰基腺嘌呤 在 sodium methylate 、 四氯化锡 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 9-(2,3-anhydro-4-C-hydroxymethyl-α-L-lyxofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine

  摘要：

  1,2-二-O-乙酰基-3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-L-阿拉伯呋喃糖与N6-苯甲酰腺嘌呤在四氯化锡催化下缩合，得到核苷I，经过部分去乙酰化和随后的甲磺酰化，转化为9-(3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-2-O-甲磺酰基-α-L-阿拉伯呋喃糖基)腺嘌呤(III)。1,2,5-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-L-阿拉伯糖与N6-苯甲酰腺嘌呤缩合，得到9-(2,5,6-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-α-L-阿拉伯呋喃糖基)-N6-苯甲酰腺嘌呤(V)。将甲烷醇钠甲醇溶液与甲磺酰衍生物III和V反应，得到2',3'-脱水核苷VIa和VIIa，它们被乙酰化，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-核糖呋喃基)腺嘌呤(VIb)和9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-吕克索呋喃基)腺嘌呤(VIIb)。环氧衍生物VIb被溴三甲基硅烷裂解成9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)腺嘌呤(VIIIa)；用环氧衍生物VIIb进行相同的反应，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-吕克索呋喃糖基)(IXa)和9-(5-O-乙酰基-4-C-乙酰氧甲基-3-溴-3-脱氧-α-L-阿拉伯呋喃糖基)(Xa)的混合物。它们通过三丁基锡脱卤素化和随后的去乙酰化，得到9-(2-脱氧-4-C-羟甲基-α-L-erythro-戊糖基)腺嘌呤(VIIIc)、9-(2-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(IXc)和9-(3-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(Xc)。通过乙酰化VIIIa得到9-(2,5-二-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)(VIIId)，经过Cu/Zn偶联还原消除和随后的去乙酰化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pent-2-enofuranosyl)腺嘌呤(XIb)。通过VIIId的催化氢化，随后去乙酰化，或者通过XIb的双脱氢衍生物的催化氢化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pentofuranosyl)腺嘌呤(XIIb)。合成的核苷类化合物被用于抗病毒活性测试。

  DOI：

  10.1135/cccc19941654

文献信息

• Novel 4′-Branched Nucleosides
  作者：S. A. Surzhykov、A. A. Krayevsky

  DOI：10.1080/15257779408013221

  日期：1994.12

  Total chemical synthesis of 4'-hydroxymethylnucleosides with an additional modification in a sugar residue was developed. The synthesis was made by condensation of corresponding protected sugars and nucleic bases with subsequent deprotection. In such a way 3'-azido- and 3'-amino-3'deoxy-4'-hydroxymethylribonucleosides, 2',3'-anhydroribo- and 2',3'-anhydrolyxo-4'-hydroxymethylribonucleosides as well as 3'-deoxy-4'hydroxymethylribollucleosides were prepared. At concentrations up to 100 mu M none of them inhibited reproduction of human immunodeficiency virus type 1 in H9 and PBL cells as well as human herpes simplex virus type 2 and human cytomegalovirus in vero cells.
• Surzhikov, S. A., Russian Journal of Bioorganic Chemistry, 1994, vol. 20, # 10, p. 626 - 634
  作者：Surzhikov, S. A.

  DOI：——

  日期：——
• Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine
  作者：Hubert Hřebabecký、Antonín Holý

  DOI：10.1135/cccc19941654

  日期：——

  Condensation of 1,2-di-O-acetyl-3,5-di-O-benzoyl-4-C-benzoyloxymethyl-L-arabinofuranose with N⁶-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I, which upon partial deacetylation and subsequent mesylation was converted into 9-(3,5-di-O-benzoyl-4-C-benzoyloxymethyl-2-O-methanesulfonyl-α-L-arabinofuranosyl)adenine (III). 9-(2,5,6-Tri-O-acetyl-4-C-acetoxymethyl-3-O-methanesulfonyl-α-L-arabinofuranosyl)-N⁶-benzoyladenine (V) was obtained by condensation of 1,2,5-tri-O-acetyl-4-C-acetoxymethyl-3-O-methanesulfonyl-L-arabinose with N⁶-benzoyladenine. Reaction of mesyl derivatives III and V with methanolic sodium methoxide afforded 2',3'-anhydro nucleosides VIa and VIIa, which were acetylated to give 9-(5-O-acetyl-4-C-acetoxymethyl-2,3-anhydro-α-L-ribofuranosyl)adenine (VIb) and 9-(5-O-acetyl-4-C-acetoxymethyl-2,3-anhydro-α-L-lyxofuranosyl)adenine (VIIb). Epoxy derivative VIb was cleaved with bromotrimethylsilane to 9-(5-O-acetyl-4-C-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (VIIIa); the same reaction with epoxy derivative VIIb afforded a mixture of 9-(5-O-acetyl-4-C-acetoxymethyl- 2-bromo-2-deoxy-α-L-xylofuranosyl)adenine (IXa) and 9-(5-O-acetyl-4-C-acetoxymethyl-3-bromo- 3-deoxy-α-L-arabinofuranosyl)adenine (Xa). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-4-C-hydroxymethyl-α-L-erythro-pentofuranosyl)adenine (VIIIc), 9-(2-deoxy-4-C-hydroxymethyl- α-L-threo-pentofuranosyl)adenine (IXc) and 9-(3-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)adenine (Xc). 9-(2,5-Di-O-acetyl-4-C-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (VIIId), prepared by acetylation of VIIIa, on reductive elimination with Cu/Zn couple and subsequent deacetylation afforded 9-(2,3-dideoxy-4-C-hydroxymethyl-α-L-glycero-pent-2-enofuranosyl)adenine (XIb). 9-(2,3-Dideoxy-4-C-hydroxymethyl-α-L-glycero-pentofuranosyl)adenine (XIIb) was obtained either by catalytic hydrogenation of bromo derivative VIIId, followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIb. The nucleosides synthesized were tested for antiviral activity.

  1,2-二-O-乙酰基-3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-L-阿拉伯呋喃糖与N6-苯甲酰腺嘌呤在四氯化锡催化下缩合，得到核苷I，经过部分去乙酰化和随后的甲磺酰化，转化为9-(3,5-二-O-苯甲酰基-4-C-苯甲酰氧甲基-2-O-甲磺酰基-α-L-阿拉伯呋喃糖基)腺嘌呤(III)。1,2,5-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-L-阿拉伯糖与N6-苯甲酰腺嘌呤缩合，得到9-(2,5,6-三-O-乙酰基-4-C-乙酰氧甲基-3-O-甲磺酰基-α-L-阿拉伯呋喃糖基)-N6-苯甲酰腺嘌呤(V)。将甲烷醇钠甲醇溶液与甲磺酰衍生物III和V反应，得到2',3'-脱水核苷VIa和VIIa，它们被乙酰化，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-核糖呋喃基)腺嘌呤(VIb)和9-(5-O-乙酰基-4-C-乙酰氧甲基-2,3-脱水-α-L-吕克索呋喃基)腺嘌呤(VIIb)。环氧衍生物VIb被溴三甲基硅烷裂解成9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)腺嘌呤(VIIIa)；用环氧衍生物VIIb进行相同的反应，得到9-(5-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-吕克索呋喃糖基)(IXa)和9-(5-O-乙酰基-4-C-乙酰氧甲基-3-溴-3-脱氧-α-L-阿拉伯呋喃糖基)(Xa)的混合物。它们通过三丁基锡脱卤素化和随后的去乙酰化，得到9-(2-脱氧-4-C-羟甲基-α-L-erythro-戊糖基)腺嘌呤(VIIIc)、9-(2-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(IXc)和9-(3-脱氧-4-C-羟甲基-α-L-threo-戊糖基)(Xc)。通过乙酰化VIIIa得到9-(2,5-二-O-乙酰基-4-C-乙酰氧甲基-2-溴-2-脱氧-α-L-阿拉伯呋喃糖基)(VIIId)，经过Cu/Zn偶联还原消除和随后的去乙酰化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pent-2-enofuranosyl)腺嘌呤(XIb)。通过VIIId的催化氢化，随后去乙酰化，或者通过XIb的双脱氢衍生物的催化氢化，得到9-(2,3-二脱氧-4-C-羟甲基-α-L-glycero-pentofuranosyl)腺嘌呤(XIIb)。合成的核苷类化合物被用于抗病毒活性测试。