6-chloro-9-(2,5-di-O-acetyl-3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine | 188883-00-3

• 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-(2,5-di-O-acetyl-3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine
• 英文别名: 6-chloro-9-(2,5-di-O-acetyl-3-deoxy-beta-D-erythro-pentofuranosyl)-9H-purine；[(2S,4R,5R)-4-acetyloxy-5-(6-chloropurin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 188883-00-3
• 化学式: C₁₄H₁₅ClN₄O₅
• 分子量: 354.75
• InChiKey: OIGRBLAWOLSABI-IMSIIYSGSA-N

物化性质

• 沸点：
  520.2±60.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(2,5-di-O-acetyl-3-deoxy-β-D-erythro-pentofuranosyl)-9H-purine 在 咪唑 、 甲醇 、 氨 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 9-[(2R,3R,5S)-3-(tert-Butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-chloro-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：
• 作为产物：
  描述：

  肌苷 在 偶氮二异丁腈 、 四乙基氯化铵 、 三正丁基氢锡 、 溶剂黄146 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 13.0h， 生成 6-chloro-9-(2,5-di-O-acetyl-3-deoxy-β-D-erythro-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

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。
• 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.
• ADENOSINE ANALOG AND ITS USE IN REGULATING THE CIRCADIAN CLOCK
  申请人：NATIONAL INSTITUTE OF BIOLOGICAL SCIENCES, BEIJING

  公开号：US20210338706A1

  公开（公告）日：2021-11-04

  The present invention provides a kind of nucleoside analogue compounds, and a composition comprising the compound and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via the compound or the composition.