2-fluoro-O⁶-methylhypoxanthine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-fluoro-O⁶-methylhypoxanthine
• 英文别名: 2-fluoro-6-methoxy-7H-purine
• 化学式: C₆H₅FN₄O
• 分子量: 168.13
• InChiKey: BLDYHZIKQICVBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N-二甲基乙酰胺 、 2-fluoro-O⁶-methylhypoxanthine 在 叔丁基过氧化氢 、 potassium iodide 作用下， 反应 10.0h， 以91%的产率得到N-((2-fluoro-6-methoxy-9H-purin-9-yl)methyl)-N-methylacetamide
  参考文献：
  名称：

  Transition-Metal-Free N9-Amidoalkylation of Purines with N,N-Dialkylamides

  摘要：

  A novel method for the selective N9-amidoalkylation of purines using N,N-dialkylamides as alkylation reagents via activation of sp(3) C-H bond adjacent to an amide nitrogen atom has been developed in the presence of KI and tert-butyl hydroperoxide (TBHP). This method was simple to operate and provided series of purine derivatives in moderate to excellent yield.

  DOI：

  10.1055/s-0036-1588134
• 作为产物：
  描述：

  2-氨基-6-甲氧基嘌呤 在 tetrafluoroboric acid 、 copper (I) fluoride 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.5h， 以64%的产率得到2-fluoro-O⁶-methylhypoxanthine
  参考文献：
  名称：

  Synthesis of Some Biologically Active Halogenopurines

  摘要：

  鸟嘌呤 (1)으로부터 생물활성이 있는 卤嘌呤 계화합물을 합성하였다.Guanine을 acetic anhydride와 반응시켜서 2,9-diacetylguanine (2-1)을 합성하여 얻어진 화합물을 $POCl_3$와 반응시켜서 화합물 3a를 합성하고, 다음 단계에서 2-amino-6-halogenopurines (3b-d)를 합성하였다.2-amino-6-substituted purines (1, 3a, 4-1)로부터 효율적으로 합성한 후에, 새로운 화합물인 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c 및 5d를 합성하였다.합성한 화합물의 구조를 원소분석, $^1H$ NMR, mass spectral data로 확인하였으며, 합성한 화합물에 대한 항균 활성을 시험하였다. 利用市售鸟嘌呤合成了一系列具有生物活性的卤代嘌呤 (1)。鸟嘌呤与乙酸酐反应，通过乙酰化反应得到 2,9-二乙酰鸟嘌呤（2-1）。在 PEG-2000 相转移催化剂的作用下，2-1 与 $POCl_3$ 进一步处理，得到了重要的化合物 3a，然后在 TPPB 相转移催化剂的作用下，通过 KX 与 3a 之间的氯交换卤化反应，得到了 2-氨基-6-卤代嘌呤（3b-d）。在相应的 CuX 催化下，2-氨基-6-取代嘌呤（1、3a、4-1）通过重氮化反应有效地制备了 2-卤代嘌呤（2-2a-d、4-2a-d、5a-d），并发现了一些新化合物 2-2a、2-2c、2-2d、4-2c、4-2d、5b、5c 和 5d。合成化合物的结构主要是根据其元素分析、$^1H$核磁共振以及质谱数据确定的。对所有标题化合物进行了抗真菌活性筛选，其中一些化合物显示出良好的活性。

  DOI：

  10.5012/jkcs.2010.54.4.429

文献信息

• Synthesis and evaluation of 3′-azido-2′,3′-dideoxypurine nucleosides as inhibitors of human immunodeficiency virus
  作者：Hong-wang Zhang、Steven J. Coats、Lavanya Bondada、Franck Amblard、Mervi Detorio、Ghazia Asif、Emilie Fromentin、Sarah Solomon、Aleksandr Obikhod、Tony Whitaker、Nicolas Sluis-Cremer、John W. Mellors、Raymond F. Schinazi

  DOI：10.1016/j.bmcl.2009.11.031

  日期：2010.1

  Based on the promising drug resistance profile and potent anti-HIV activity of β-d-3′-azido-2′,3′-dideoxyguanosine, a series of purine modified nucleosides were synthesized by a chemical transglycosylation reaction and evaluated for their antiviral activity, cytotoxicity, and intracellular metabolism. Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes

  基于 β- d -3'-azido-2',3'-dideoxyguanosine具有良好的耐药性和强大的抗 HIV 活性，通过化学转糖基化反应合成了一系列嘌呤修饰的核苷，并评估了它们的抗病毒活性、细胞毒性和细胞内代谢。在合成的化合物中，有几种在原代淋巴细胞中显示出有效和选择性的抗 HIV 活性。
• [EN] NUCLEOSIDE AND NUCLEOTIDE ANALOGUES BEARING A QUATERNARY ALL-CARBON STEREOGENIC CENTER AT THE 2' POSITION AND METHODS OF USE AS A CARDIOPROTECTIVE AGENT<br/>[FR] ANALOGUES DE NUCLÉOSIDES ET DE NUCLÉOTIDES PORTANT UN CENTRE STÉRÉOGÈNE TOUT CARBONE QUATERNAIRE EN POSITION 2' ET PROCÉDÉS D'UTILISATION EN TANT QU'AGENT CARDIOPROTECTEUR
  申请人：LCB PHARMA INC

  公开号：WO2018049534A1

  公开（公告）日：2018-03-22

  Nucleoside and nucleotide analogues that can be used as cardioprotective agents are provided. The nucleosides and nucleotide analogues comprise tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary stereogenic all-carbon centers at the 2' position and a phosphonate ester at the 5' position.

  提供可用作心脏保护剂的核苷和核苷酸类似物。这些核苷和核苷酸类似物包括在2'位置具有四氢呋喃基或四氢噻吩基的四面体立体异构所有碳中心，以及在5'位置具有磷酸酯基。
• Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine for detection by GC-EC/MS
  作者：Chingchen S. Chiu、Manasi. Saha、Amir. Abushamaa、Roger W. Giese

  DOI：10.1021/ac00069a021

  日期：1993.11.1

  In this project we set out to make an important class of DNA adducts, comprising O6-alkyl and O6-(hydroxyalkyl)guanines, susceptible to sensitive detection by GC-EC/MS. While existing literature indicated that pentafluorobenzylation would be useful for the ring NH site on these compounds, how to best overcome the polarity of the exocyclic NH2 and OH groups, without losing the O6-alkyl moiety, was less clear. Working with O6-methylguanine and O6-(2'-hydroxyethyl)guanine as representative analytes, we found that the NH2 group could be converted into fluoro without loss of the O6 substituent. For the OH group, a comparison of several derivatives (OR') led to R' = tert-butyl as the best choice at this stage. The latter work, especially via NMR, also allowed exact structural assignments to be made for the N7 and N9 pentafluorobenzyl isomeric derivatives that formed. Of these R' derivatives, the N7 isomers migrated slower on silica-TLC, had higher GC retention times, had lower responses by GC-EC/MS, and were preferentially destroyed as the GC column aged. However, the N9 isomer was slower on TLC when the OH was not derivatized. This behavior was rationalized using a concept of ''polar footprint'' for the derivatives. The concept also seemed to explain the puzzling GC-EC/MS behavior of some related compounds in our laboratory. Apparently the polar footprint should be minimized in designing derivatives for trace detection by GC-EC/MS.
• NUCLEOSIDE AND NUCLEOTIDE ANALOGUES BEARING A QUATERNARY ALL-CARBON STEREOGENIC CENTER AT THE 2' POSITION AND METHODS OF USE AS A CARDIOPROTECTIVE AGENT
  申请人：LCB Pharma Inc.

  公开号：EP3512860B1

  公开（公告）日：2020-11-25
• Transition-Metal-Free N9-Amidoalkylation of Purines with N,N-Dialkylamides
  作者：Dongen Lin、Saiyu Xu、Zheng Luo、Ziyang Jiang

  DOI：10.1055/s-0036-1588134

  日期：——

  A novel method for the selective N9-amidoalkylation of purines using N,N-dialkylamides as alkylation reagents via activation of sp(3) C-H bond adjacent to an amide nitrogen atom has been developed in the presence of KI and tert-butyl hydroperoxide (TBHP). This method was simple to operate and provided series of purine derivatives in moderate to excellent yield.