3-[2-deoxy-β-D-ribofuranosyl]-furo[2,3-d]pyrimidin-2(3H)-one | 139546-03-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-[2-deoxy-β-D-ribofuranosyl]-furo[2,3-d]pyrimidin-2(3H)-one
• 英文别名: 5-(2'-deoxy-β-D-ribofuranosyl)furano[2,3-d]pyrimidine-6(5H)-one；3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]furo[2,3-d]pyrimidin-2-one；3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]furo[2,3-d]pyrimidin-2-one
• CAS: 139546-03-5
• 化学式: C₁₁H₁₂N₂O₅
• 分子量: 252.227
• InChiKey: NPBLHAAOWBLIFR-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[2-deoxy-β-D-ribofuranosyl]-furo[2,3-d]pyrimidin-2(3H)-one 在 氢溴酸 、 溴化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以65%的产率得到溴夫定
  参考文献：
  名称：

  溴夫定的新合成工艺、溴夫定

  摘要：

  本发明公开了一种溴夫定的新合成工艺、溴夫定，包括以下步骤：以β‑胸苷为起始原料，将β‑胸苷与DMF‑DMA进行甲酰化反应，生成中间体一，将中间体一与乙酸加热成环，生成中间体二，再将中间体二与氢溴酸反应，获得溴夫定。本发明的溴夫定的新合成工艺，首先将β‑胸苷与DMF‑DMA进行甲酰化反应，再与乙酸加热成环，最后与氢溴酸反应开环制得溴夫定。上述以β‑胸苷为起始原料，起始物料价格便宜、容易获得，不需要使用昂贵的钯作为催化剂，可有效降低溴夫定的原料成本。上述溴夫定的合成路线短，条件温和，便于操作，适合工业化生产。

  公开号：

  CN113234112B
• 作为产物：
  描述：

  5-(1-hydroxy-2-chloroethyl)-3',5'-di-O-acetyl-2'-deoxyuridine 在 二乙胺基三氟化硫 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.42h， 生成 3-[2-deoxy-β-D-ribofuranosyl]-furo[2,3-d]pyrimidin-2(3H)-one
  参考文献：
  名称：

  5-（1,2-二卤乙基）-2'-脱氧尿苷及相关类似物的合成及性质

  摘要：

  AbstractThe regiospecific reaction of 5‐vinyl‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (2) with HOX (X = Cl, Br, I) yielded the corresponding 5‐(1‐hydroxy‐2‐haloethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridines 3a‐c. Alternatively, reaction of 2 with iodine monochloride in aqueous acetonitrile also afforded 5‐(1‐hydroxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3c). Treatment of 5‐(1‐hydroxy‐2‐chloroethyl)‐ (3a) and 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with DAST (Et2NSF3) in methylene chloride at ‐40° gave the respective 5‐(1‐fluoro‐2‐chloroethyl)‐ (6a, 74%) and 5‐(1‐fluoro‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6b, 65%). In contrast, 5‐(1‐fluoro‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6e) could not be isolated due to its facile reaction with methanol, ethanol or water to yield the corresponding 5‐(1‐methoxy‐2‐iodoethyl)‐ (6c), 5‐(1‐ethoxy‐2‐iodoethyl)‐ (6d) and 5‐(1‐hydroxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3c). Treatment of 5‐(1‐hydroxy‐2‐chloroethyl)‐ (3a) and 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with thionyl chloride yielded the respective 5‐(1,2‐dichloroethyl)‐ (6f, 85%) and 5‐(1‐chloro‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6g, 50%), whereas a similar reaction employing the 5‐(1‐hydroxy‐2‐iodoethyl)‐ compound 3c afforded 5‐(1‐methoxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6c), possibly via the unstable 5‐(1‐chloro‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine intermediate 6h. The 5‐(1‐bromo‐2‐chloroethyl)‐ (6i) and 5‐(1,2‐dibromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6j) could not be isolated due to their facile conversion to the corresponding 5‐(1‐ethoxy‐2‐chloroethyl)‐ (6k) and 5‐(1‐ethoxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (61). Reaction of 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with methanolic ammonia, to remove the 3′,5′‐di‐O‐acetyl groups, gave 2,3‐dihydro‐3‐hydroxy‐5‐(2′‐deoxy‐β‐D‐ribofuranosyl)‐furano[2,3‐d]pyrimidine‐6(5H)‐one (8). In contrast, a similar reaction of 5‐(1‐fluoro‐2‐chloroethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6a) yielded (E)‐5‐(2‐chlorovinyl)‐2′‐deoxyuridine (1b, 23%) and 5‐(2′‐deoxy‐β‐D‐ribofuranosyl)furano[2,3‐d]pyrimidin‐6(5H)‐one (9, 13%). The mechanisms of the substitution and elimination reactions observed for these 5‐(1,2‐dihaloethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridines are described.

  DOI：

  10.1002/jhet.5570280819

文献信息

• Synthesis of 5-(1-azidovinyl) and 5-[2-(1-azirinyl)] analogs of 2′-deoxyuridine
  作者：Rakesh Kumar、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1139/v96-178

  日期：1996.9.1

  The regiospecific addition of bromine azide to the vinyl substituent of 5-vinyl-3′,5′-di-O-acetyl- (or tert-butyldimethylsilyl)-2′-deoxyuridines (2) yielded the corresponding 5-(1-azido-2-bromoethyl)-3′,5′-di-O-protected-2′-deoxyuridines (3). Treatment of the 5-(1-azido-2-bromoethyl) compounds 3 with t-BuOK, to effect the base-catalyzed elimination of HBr, afforded the corresponding 5-(1-azidovinyl)-2′-deoxyuridines (4, 7). Thermal decomposition of 5-(1-azidovinyl)-2′-deoxyuridine (7) at 110 °C in dioxane yielded 5-[2-(1 -azirinyl)]-2′-deoxyuridine (9). 5-(1 -Azidovinyl)-2′-deoxyuridine (7) exhibited appreciable in vitro antiviral activities againist herpes simplex virus type 1 (HSV-1) and varizella zoster virus (VZV). Athough 7 increased the length of survival of HSV-1 brain-infected mice, it did not decrease the mortality rate relative to placebo. 5-[2-(1-Azirinyl)]-2′-deoxyuridine (9) was an inactive antiviral agent. Key words: azidovinyl, azirinyl, 2′-deoxyuridine, antiviral activity.

  溴化物对5-乙烯基-3′,5′-二-O-乙酰基-(或叔丁基二甲基硅基)-2′-脱氧尿苷（2）的乙烯基取代物的区域特异性加成产生相应的5-(1-叠氮基-2-溴乙基)-3′,5′-二-O-保护基-2′-脱氧尿苷（3）。用t-BuOK处理5-(1-叠氮基-2-溴乙基)化合物3，以实现碱催化的HBr消除，得到相应的5-(1-叠氮基乙烯基)-2′-脱氧尿苷（4, 7）。在二噁烷中将5-(1-叠氮基乙烯基)-2′-脱氧尿苷（7）在110°C下热分解，得到5-[2-(1-环氧基)]-2′-脱氧尿苷（9）。5-(1-叠氮基乙烯基)-2′-脱氧尿苷（7）在体外表现出对单纯疱疹病毒1型（HSV-1）和水痘-带状疱疹病毒（VZV）的可观抗病毒活性。尽管7延长了HSV-1感染小鼠的存活时间，但与安慰剂相比，未降低死亡率。5-[2-(1-环氧基)]-2′-脱氧尿苷（9）是一种无活性的抗病毒剂。关键词：叠氮基乙烯基，环氧基，2′-脱氧尿苷，抗病毒活性。
• Synthesis and properties of oligonucleotides containing a 2,6-diamino-3-deazapurine:furanopyrimidine base pair
  作者：Koki Matsumoto、Noriko Saito-Tarashima、Tomoya Wada、Orie Yonaha、Noriaki Minakawa

  DOI：10.1080/15257770.2019.1694687

  日期：2022.10.3

  of base pair in an oligodeoxynucleotide (ODN) duplex, they were incorporated into ODNs, and the Tm value of the ODN duplex was determined. However, the ODN duplex containing a DC3Pu:FPy pair has a lower thermal stability than that containing a G:C pair does, although its thermal stability is equal to that of an ODN duplex with an A:T pair even under acidic conditions.

  摘要 分别制备了能够在 DDD 和 AAA H 键模式中相互作用的呋喃嘧啶 (FPy) 和 2,6-二氨基-3-脱氮嘌呤 (DC 3 Pu) 核苷。DC 3 Pu 核苷的 N-1 p K a值估计为 6.4，这是由于在 3 位缺少氮原子，表明 DC 3 Pu 作为碱基在 DDD H 中相互作用-在接近生理条件下的键合模式。由于 DC 3 Pu 和 FPy 预计会在寡脱氧核苷酸 (ODN) 双链体中形成热稳定的 DDD:AAA 型碱基对，因此将它们掺入 ODN，并确定 ODN 双链体的T m值。然而，ODN 双工包含一个 DC3 Pu:FPy 对的热稳定性低于包含 G:C 对的热稳定性，尽管即使在酸性条件下，其热稳定性也与具有 A:T 对的 ODN 双链体相同。
• Fluorescent nitrogenous base and nucleosides incorporating same
  申请人：Glen Research Corporation

  公开号：US20040009933A1

  公开（公告）日：2004-01-15

  A fluorescent nitrogenous base and nucleosides including the fluorescent nitrogenous base are provided. Nucleosides including the fluorescent nitrogenous base are capable of Watson-Crick base pairing with naturally occurring nucleosides. The nucleosides including the fluorescent nitrogenous base have many uses including but not limited to use in probes, in the synthesis of nucleic acids, and in investigating nucleic acid interactions with other nucleic acids and/or with proteins.

  本研究提供了一种荧光含氮碱基和包括荧光含氮碱基的核苷。 包括荧光含氮碱基的核苷能够与天然存在的核苷进行沃森-克里克碱基配对。 包括荧光含氮碱基的核苷具有多种用途，包括但不限于用于探针、核酸合成以及研究核酸与其他核酸和/或蛋白质的相互作用。
• Design and Studies of Novel 5-Substituted Alkynylpyrimidine Nucleosides as Potent Inhibitors of Mycobacteria
  作者：Dinesh Rai、Monika Johar、Tracey Manning、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm058167w

  日期：2005.11.1

  We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.
• FLUORESCENT NITROGENOUS BASE AND NUCLEOSIDES INCORPORATING SAME
  申请人：Glen Research Corporation

  公开号：EP1483280B1

  公开（公告）日：2012-10-24