1-(2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl)thymine | 179238-65-4

• 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: 1-(2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl)thymine
• 英文别名: 1-[(2R,4R)-4-hydroxy-5-methylideneoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 179238-65-4
• 化学式: C₁₀H₁₂N₂O₄
• 分子量: 224.216
• InChiKey: GHLYSDYPUZQXIN-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl)thymine 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.0h， 生成 [(3R)-3-[tert-butyl(dimethyl)silyl]oxy-2,5-dioxopentyl] acetate
  参考文献：
  名称：

  Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine

  摘要：

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.

  DOI：

  10.1021/jo060194m
• 作为产物：
  描述：

  3',4'-anhydrothymidine 在 敌草腈 、 氨 、 sodium iodide 作用下， 以 吡啶 、 甲醇 、 溶剂黄146 、 乙腈 为溶剂， 反应 39.5h， 生成 1-(2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl)thymine
  参考文献：
  名称：

  Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine

  摘要：

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.

  DOI：

  10.1021/jo060194m

文献信息

• Electrophile-promoted addition of hydroxymethylphosphonate to 4′,5′-didehydronucleosides: a way to novel isosteric analogues of 5′-nucleotides
  作者：Zdeněk Točík、Ivana Dvořáková、Radek Liboska、Miloš Buděšínský、Milena Masojídková、Ivan Rosenberg

  DOI：10.1016/j.tet.2007.03.059

  日期：2007.5

  addition of dialkyl-hydroxymethylphosphonate to the protected 4′,5′-didehydronucleosides resulted in an epimeric mixture of 4′-dialkylphosphonomethoxy derivatives of 2′,5′-dideoxynucleosides, novel analogues of 2′-deoxynucleoside 5′-monophosphates. Several types of electrophiles (pyridinium tosylate, NIS, NBS, MCPBA and others) were evaluated in addition reactions with 4′,5′-didehydrothymidine. Out

  亲电子促进的将二烷基羟甲基膦酸酯加到受保护的4'，5'-didehydronucleosides上，生成2'，5'-dideoxynucleosides的4'-di烷基膦酰基甲氧基衍生物的差向异构体混合物，这是2'-deoxynucleoside 5'-monophosphates的新类似物。在与4'，5'-二氢胸苷的加成反应中评估了几种类型的亲电试剂（甲苯磺酸吡啶鎓，NIS，NBS，MCPBA等）。从中发现，甲苯磺酸吡啶鎓在这些转化中具有实际用途。它的使用导致了一系列常见2'-脱氧核苷的4'-膦酰基甲氧基衍生物的制备。在生物学筛选中，这些游离膦酸没有发挥明显的细胞抑制或抗病毒活性。
• Synthesis of New 5″-Sulfonylamido Derivatives of 3″-Azido-3″-Deoxythymidine (AZT)
  作者：Wojciech Urjasz、Lech Celewicz、Krzysztof Golankiewicz

  DOI：10.1080/07328319608007387

  日期：1996.6

  A series of 5'-N-methanesulfonyl derivatives of 3'-azido-5'-(alkylamino)-3',5'-dideoxythymidine was synthesised. The first step of the synthesis involved the reaction of 1-(2,5-dideoxy-5-O-tosyl-beta-D-threo-pentofuranosyl)thymine 1 with an appropriate amine to give 1-[5-(alkylamino)-2,5-dideoxy-beta-D-threo-pentofuranosyl]thymine 2a-e and 1-(2,5-dideoxy-beta-threo-pent-4-enofuranosyl)thymine 3 as a by-product. Compounds 2a-e were treated with an excess of methanesulfonyl chloride to yield intermediates 1-[5-(dimethylamino)-3-O-methanesulfonyl-2,3,5-trideoxy-beta-D-threo-pentofuranosyl]thymine 4a and 1-[5-(N-alkyl-N-methanesulfonyl)-3-O-methanesulfonyl-2,3,5-trideoxy-beta-D-threo-penfuranosyl]thymines 4b-e. The reaction of 4a-e with lithium azide in dimethylformamide afforded the final compounds 1-[3-azido-5-(N-methyl-N-methanesulfonyl)-2,3,5-trideoxy-beta-D-erythro-penofuranosyl]thymine 5a and 1-[3-azido-5-(N-alkyl-N-methanesulfonyl)-2,3,5-trideoxy-beta-D-erythro-penofuranosyl]thymines 5b-e. The independent synthesis of 4',5'-unsaturated product 3 was also described.
• Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine
  作者：Kazuhiro Haraguchi、Masanori Sumino、Hiromichi Tanaka

  DOI：10.1021/jo060194m

  日期：2006.6.1

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.