Methanesulfonic acid (2R,4S)-8,8-dimethyl-2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-1,7,9-trioxa-spiro[4.5]dec-4-yl ester | 139925-87-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: Methanesulfonic acid (2R,4S)-8,8-dimethyl-2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-1,7,9-trioxa-spiro[4.5]dec-4-yl ester
• 英文别名: 1-<(6R,8R)-8-methanesulfonyloxy-2,2-dimethyl-1,3,5-trioxaspiro<3.4>oct-6-yl>thymine；1-((6R,8R)-8-methanesulfonyloxy-2,2-dimethyl-1,3,5-trioxaspiro[3.4]oct-6-yl)thymine
• CAS: 139925-87-4；148765-99-5
• 化学式: C₁₅H₂₂N₂O₈S
• 分子量: 390.414
• InChiKey: ULVHTWVSSXBDRK-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.37
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  125.92
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  Methanesulfonic acid (2R,4S)-8,8-dimethyl-2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-1,7,9-trioxa-spiro[4.5]dec-4-yl ester 在 叠氮化锂 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 Thymidine, 2',3'-didehydro-3'-deoxy-4'-[[(methylsulfonyl)oxy]methyl]-
  参考文献：
  名称：

  4′-Substituted nucleosides as inhibitors of HIV: an unusual oxetane derivative.

  摘要：

  The fused oxetane derivative of thymidine 3a inhibits HIV replication in A301 (Alex) cells with remarkably low bone marrow toxicity.

  DOI：

  10.1016/s0040-4039(00)77668-4
• 作为产物：
  描述：

  3'-O-(tert-butyldimethylsilyl)-4'-(hydroxymethyl)-thymidine 在 sodium hydroxide 、 二(4-硝基苯基)次膦酸 、 氢氟酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 Methanesulfonic acid (2R,4S)-8,8-dimethyl-2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-1,7,9-trioxa-spiro[4.5]dec-4-yl ester
  参考文献：
  名称：

  4′-Substituted nucleosides as inhibitors of HIV: an unusual oxetane derivative.

  摘要：

  The fused oxetane derivative of thymidine 3a inhibits HIV replication in A301 (Alex) cells with remarkably low bone marrow toxicity.

  DOI：

  10.1016/s0040-4039(00)77668-4

文献信息

• Synthesis of 1-(3-Azido-2,3-dideoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)thymine, 1-(2,3-Dideoxy-4-C-hydroxymethyl-α-L-glycero-pentofuranosyl)thymine and 1-(2,3-Dideoxy-4-C-hydroxymethyl-α-L-glycero-pent-2-enofuranosyl)thymine
  作者：Hubert Hřebabecký、Antonín Holý

  DOI：10.1135/cccc19930409

  日期：——

  1-(2-O-Acetyl-3,5-di-O-benzoyl-4-C-benzoyloxymethyl-α-L-arabinofuranosyl)thymine (II) was converted to 2,2'-anhydro derivative V by selective deacetylation, mesylation and treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene. Cleavage of 2,2'-anhydro ring in compound V with hydrogen chloride or bromide afforded the respective 2'-chloro and 2'-bromo derivatives VI and VII. Reaction of compound VII with Cu/Zn couple and subsequent debenzoylation led to 1-(2,3-dideoxy-4-C-hydroxymethyl-α-L-pent-2-enofuranosyl)thymine (IX). Catalytic hydrogenation of IX gave 1-(2,3-dideoxy-4-C-hydroxymethyl-α-L-glycero-pentofuranosyl)thymine (X). Dehalogenation of compound VI with tributyltin hydride and debenzoylation afforded 1-(2-deoxy-4-C-hydroxymethyl-α-L-erythro-pentofuranosyl)thymine (XII). Tritylation of compound XII, followed by mesylation, detritylation and nucleophilic substitution with azide furnished 1-(3-azido-2,3-dideoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)thymine (XXII).

  1-(2-O-乙酰基-3,5-二-O-苯甲酰基-4-C-苯氧甲基-α-L-阿拉伯呋喃糖基)嘧啶(II)经选择性去乙酰化、甲磺酰化和与1,8-二氮杂双环[5.4.0]十一烯处理转化为2,2'-脱水衍生物V。用氯化氢或溴化氢裂解化合物V中的2,2'-脱水环得到相应的2'-氯和2'-溴衍生物VI和VII。化合物VII与Cu/Zn偶对反应，随后脱苯甲酰化导致1-(2,3-二脱氧-4-C-羟甲基-α-L-戊-2-烯呋喃糖基)嘧啶(IX)。对IX进行催化氢化得到1-(2,3-二脱氧-4-C-羟甲基-α-L-甘油-戊呋喃糖基)嘧啶(X)。用三丁基锡氢化合物VI并脱苯甲酰化得到1-(2-脱氧-4-C-羟甲基-α-L-赤霉-戊呋喃糖基)嘧啶(XII)。化合物XII的三苯甲基化，随后甲磺酰化、去三苯甲基化和亲核取代与叠氮化合物反应得到1-(3-叠氮基-2,3-二脱氧-4-C-羟甲基-α-L-顺-戊呋喃糖基)嘧啶(XXII)。