6-chloro-9-(3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine | 6982-08-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-chloro-9-(3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine
• 英文别名: (2R,3R,5S)-2-(6-chloropurin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3R,5S)-2-(6-chloropurin-9-yl)-5-(hydroxymethyl)oxolan-3-ol
• CAS: 6982-08-7
• 化学式: C₁₀H₁₁ClN₄O₃
• 分子量: 270.675
• InChiKey: GTFKHUYSYOGXNT-BAJZRUMYSA-N

物化性质

• 沸点：
  568.0±60.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine 在 吡啶 、 2,4,6-三甲基吡啶 、 二乙胺基三氟化硫 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.0h， 生成 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(triphenylmethyl)-β-D-threo-pentofuranosyl]-9H-purine
  参考文献：
  名称：

  经由嘌呤3'-脱氧核苷合成9-（2,3-二脱氧-2-氟-β-D-苏-戊呋喃糖基）腺嘌呤（FddA）。

  摘要：

  经由6-氯-9-（3-脱氧-β-D-赤型-五氟呋喃糖基）合成9-（2,3-二脱氧-2-氟-β-D-苏-五呋喃糖基）腺嘌呤（1，FddA）描述了易于从肌苷（5）获得的）-9H-嘌呤（9）。通过引入6-氯基团可以改善嘌呤3'-脱氧核苷的C2'-β位置与三乙二氨基氨基硫的氟化作用，并且产率中等。嘌呤3'-脱氧核苷衍生物也与三乙胺三氟化氢进行亲核反应，并以良好的收率得到所需的氟化核苷。通过使用三乙胺三氟化氢大大提高了氟化工艺的安全性和产率。

  DOI：

  10.1021/jo0158985
• 作为产物：
  描述：

  虫草素 在 吡啶 、 盐酸 、 甲醇 、 氯化亚砜 、 氨 、 adenosine deaminase 作用下， 以 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 6-chloro-9-(3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine
  参考文献：
  名称：

  Kumamoto, Hiroki; Hayakawa, Hiroyuki; Tanaka, Hiromichi, Nucleosides and Nucleotides, 1998, vol. 17, # 1-3, p. 15 - 27

  摘要：

  DOI：

文献信息

• Practical synthesis of 9-(2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine (FddA) via a purine 3′-deoxynucleoside
  作者：Satoshi Takamatsu、Tokumi Maruyama、Satoshi Katayama、Naoko Hirose、Masaki Naito、Kunisuke Izawa

  DOI：10.1016/s0040-4039(01)00136-8

  日期：2001.3

  A practical synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (1, FddA) via a 6-chloro-9-(3-deoxy-β-d-erythro-pentofuranosyl)-9H-purine (6) is described. Fluorination at the C2′-β position of the purine 3′-deoxynucleoside was improved by the introduction of 6-chloro group, and proceeded in moderate yield. The total yield of FddA from readily available starting material 6 was 35%

  9-（2,3-二脱氧-2-氟-β-D-的实际合成苏-pentofuranosyl）腺嘌呤（1经由6-氯-9-（3-脱氧β-D-，FDDA）赤-呋喃戊糖基）-9 ħ嘌呤（6）进行说明。嘌呤3'-脱氧核苷C2'-β位置的氟化反应通过引入6-氯基得以改善，并以中等收率进行。来自容易获得的起始原料6的FddA的总产率为35％。
• Methods for producing nucleoside derivatives and intermediates therefor
  申请人：Ajinomoto Co., Inc.

  公开号：US06090937A1

  公开（公告）日：2000-07-18

  Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3'-position of the saccharide moiety is deoxylated, can be substituted at the 2'-position at an extremely high yield. Specifically, by subjecting a 3'-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2'-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield. Methods for producing nucleoside derivatives including 9-(2,3-dideoxy-2-fluoro-.beta.-D-threo-pentofuranosyl)adenine (FddA) and their related compounds, in a simplified manner, at a high yield and at low costs, and especially Economical methods for substituting substrates, of which the 3'-position of the saccharide moiety is deoxylated, at the 2'-position to produce those nucleoside derivatives on an industrial scale are also provided.

  生产新型核苷衍生物的中间体，其中核酸碱基部分的6位被卤素原子取代。利用这些新型中间体，即使脱氧糖苷部分的3'-位也可以以极高的产率在2'-位进行取代。具体来说，通过将肌苷的3'-脱氧衍生物经过6-卤化处理，得到该衍生物的6-卤化物，然后进行2'-脱氧化/以氟原子等进行取代，随后进一步进行6-位卤素原子处的氨基团、羟基或其他取代基的取代，可以高产率地生产核苷衍生物。提供了一种简化方式、高产率、低成本地生产包括9-(2,3-脱氧-2-氟-β-D-巯基-戊呋糖基)腺嘌呤（FddA）及其相关化合物的核苷衍生物的方法，特别是提供了一种经济的方法，用于在工业规模上取代脱氧糖苷部分的3'-位以在2'-位生产这些核苷衍生物。
• Methods for producing nucleoside derivatives and intermediates therefore
  申请人：Ajinomoto Co., Inc.

  公开号：EP0945460A1

  公开（公告）日：1999-09-29

  Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3'-position of the saccharide moiety is deoxylated, can be substituted at the 2'-position at an extremely high yield. Specifically, by subjecting a 3'-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2'-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield. Methods for producing nucleoside derivatives including 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)adenine (FddA) and their related compounds, in a simplified manner, at a high yield and at low costs , and especially Economical methods for substituting substrates, of which the 3'-position of the saccharide moiety is deoxylated, at the 2'-position to produce those nucleoside derivatives on an industrial scale are also provided.

  生产出了核苷衍生物的新型中间体，其中核酸碱基的 6 位被卤原子取代。利用这些新型中间体，即使是糖基的 3'- 位被脱氧的底物，也能以极高的产率在 2'- 位被取代。具体来说，将肌苷的 3'-脱氧衍生物进行 6-卤化，得到该衍生物的 6-卤化物，然后将其进行 2'-脱氧/与氟原子或类似物进行取代，再将其与氨基、羟基或 6-位卤原子上的任何其他预期取代基进行取代，就能以高产率生产出核苷衍生物。 本发明还提供了以简化的方式、高产率和低成本生产核苷衍生物（包括 9-(2,3-二脱氧-2-氟-β-D-三呋喃戊糖基)腺嘌呤 (FddA)及其相关化合物）的方法，特别是在 2'-位上取代糖基 3'-位脱氧的底物以工业规模生产这些核苷衍生物的经济方法。
• SYNTHESIS AND<i>IN VITRO</i>ANTIVIRAL ACTIVITY EVALUATION OF 9-(2-AZIDO-2,3-DIDEOXY-β-D-<i>THREO</i>-PENTOFURANOSYL)ADENINE DERIVATIVES
  作者：Satoshi Takamatsu、Kunisuke Izawa、Tokumi Maruyama、Satoshi Katayama、Naoko Hirose、Erik De Clercq

  DOI：10.1081/ncn-100002490

  日期：2001.3.31

  9-(2-Azido-2,3-dideoxy-beta -D-threo-pentofuranosyl)adenine derivatives (la-e) containing a lipophilic function at the N-6 position in the purine ring were prepared and evaluated for their antiviral activity. The compounds 1a-e turned out to be inactive as antiviral agents.
• An Industrial Process for Synthesizing Lodenosine (FddA)
  作者：Kunisuke Izawa、Satoshi Takamatsu、Satoshi Katayama、Naoko Hirose、Shigetaka Kozai、Tokumi Maruyama

  DOI：10.1081/ncn-120021951

  日期：2003.10

  Two industrial synthetic approaches to Lodenosine (1, FddA, 9-(2,3-dideoxy-2-fluoro-p-D-threo-pentofuranosyl) adenine) via a purine riboside or a purine 3'-deoxyriboside are described. Several novel applications of deoxygenation and fluorination methods are compared considering reaction yields, economy, safety and environmental concerns.