9-[2-deoxy-3,5-di-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-6-iodopurine | 756494-16-3

• 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: 9-[2-deoxy-3,5-di-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-6-iodopurine
• 英文别名: 6-iodo-9-(2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl)purine；9-(3,5-di-O-p-toluoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-iodopurine；9-(2,5-di-O-p-toluoyl-2-deoxy-β-D-erythro-petofuranosyl)-6-iodopurine；6-iodo-9-(2-deoxy-3,5-di-O-toluoyl-β-D-erythro-pentofuranosyl)purine；9-(3,5-di-O-para-toluyl-β-D-2'-deoxyribofuranosyl)-6-iodopurine；[(2R,3S,5R)-5-(6-iodopurin-9-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 756494-16-3
• 化学式: C₂₆H₂₃IN₄O₅
• 分子量: 598.397
• InChiKey: LGDKMBMVVQATLF-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  9-[2-deoxy-3,5-di-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-6-iodopurine 在 palladium on activated charcoal 、 tris(dibenzylideneacetone)dipalladium (0) lithium hydroxide 、 copper(l) iodide 、 三苯胂 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-3-{4-[9-(2-deoxy-β-D-erythro-pentofuranosyl)purin-6-yl]phenyl}-2-aminopropanoic acid
  参考文献：
  名称：

  对映体纯（Purin-6-基）苯丙氨酸及其核苷，一种新型的嘌呤氨基酸缀合物的合成。

  摘要：

  对映体或非对映体纯的4-（嘌呤-6-基）苯丙氨酸，一种新型的稳定氨基酸-嘌呤偶联物，是通过钯催化的受保护的4-硼硼烷苯丙氨酸或4-（三甲基锡烷基）苯丙氨酸与不同的交叉偶联反应而合成的。 6-卤尿嘧啶（9-苄基-6-卤尿嘧啶和9-（四氢吡喃-2-基）-6-卤尿嘧啶以及酰基和甲硅烷基保护的6-卤代嘌呤核糖核苷和2-脱氧核糖核苷）。交叉偶联反应产物完全脱保护后，获得6位带有（S）-或（R）-苯丙氨酸的游离嘌呤碱基和核苷。这些交叉偶联和脱保护方案的反应性趋势已在实用性，效率和立体选择性方面进行了比较。

  DOI：

  10.1021/jo051110x
• 作为产物：
  描述：

  对甲基苯甲酰氯 在 吡啶 、 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 三氟乙酸 、 sodium iodide 、 三氯氧磷 作用下， 以 乙腈 、 丁酮 为溶剂， 反应 7.17h， 生成 9-[2-deoxy-3,5-di-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-6-iodopurine
  参考文献：
  名称：

  S_NAr Iodination of 6-Chloropurine Nucleosides:  Aromatic Finkelstein Reactions at Temperatures Below −40 °C¹

  摘要：

  Mesitoyl or toluoyl esters of inosine and 2'-deoxyinosine were deoxychlorinated at C6 to give the crystalline 6-chloropurine nucleoside derivatives, which underwent quantitative conversion to the 6-iodo analogues with Nal/TFA/butanone at -50 to -40 degreesC. The 6-iodo compounds were efficient substrates for SNAr, Sonogashira, and Suzuki-Miyaura reactions, in contrast with the 6-chloro analogues, and gave good to high yields of C-N and C-C coupled products.

  DOI：

  10.1021/ol048987n

文献信息

• Facile and Efficient Synthesis of 6-(Hydroxymethyl)purines
  作者：Peter Šilhár、Radek Pohl、Ivan Votruba、Michal Hocek

  DOI：10.1021/ol049059r

  日期：2004.9.1

  [reaction: see text] A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines with acyloxymethylzinc iodides followed by deprotection. Several title compounds are inhibitors of adenosine deaminase and exert cytostatic activity.

  [反应：见正文]基于6-卤尿烷与酰氧基甲基锌碘化物的钯催化交叉偶联反应，然后脱保护，开发了一种简便而有效的合成6-（羟甲基）嘌呤衍生物（碱和核苷）的方法。几种标题化合物是腺苷脱氨酶的抑制剂，并具有抑制细胞生长的活性。
• Preparation and Crystal Structures of ­Purine 2,2′-, 6,6′-, and 8,8′-Dimers
  作者：Tomáš Tobrman、Petr Štěpnička、Ivana Císařová、Dalimil Dvořák

  DOI：10.1002/ejoc.200800017

  日期：2008.4

  N-dimethylformamide affords the corresponding 6,6′-, 2,2′-, and 8,8′-purine dimers in high yield. Cross-dimerization reactions of different iodo derivatives were attempted, but only mixtures containing the cross-coupled products, homodimers, or dehalogenation products were obtained. The crystal structures of 9,9′-dibenzyl- (1a) and 9,9′-bis(1-methylethyl)-9H,9′H-[6,6′]bipurinyl (1c) and the salt [1aH2]Br2

  在 N,N-二甲基甲酰胺中用噻吩-2-羧酸铜 (I) 或 3-甲基水杨酸铜 (I) 处理 9-或 7-取代的 6-、2- 或 8-碘嘌呤衍生物，得到相应的 6,6' -、2,2'- 和 8,8'- 嘌呤二聚体的高产率。尝试了不同碘衍生物的交叉二聚反应，但只获得了包含交叉偶联产物、同二聚体或脱卤产物的混合物。9,9'-二苄基-(1a)和9,9'-双(1-甲基乙基)-9H,9'H-[6,6']联嘌呤基(1c)及其盐[1aH2]Br2的晶体结构由单晶 X 射线衍射分析确定，揭示了广泛的氢键和 π···π 堆积相互作用。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
• Synthesis of 2-Substituted 6-(Hydroxymethyl)purine Bases and Nucleosides
  作者：Peter Šilhár、Radek Pohl、Ivan Votruba、Michal Hocek

  DOI：10.1135/cccc20051669

  日期：——

  A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines or N-protected 2-amino-6-halopurines with (benzoyloxymethyl)zinc iodide followed by deprotection. Regioselective hydroxymethylations of 2,6-dihalopurines were also studied and used for the synthesis of 2-chloro-6-(hydroxymethyl)- or 2,6-bis(hydroxymethyl)purines. The 6-(hydroxymethyl)purine ribonucleoside 5f exerted high cytostatic effect and moderate inhibition of adenosine deaminase, while all the other derivatives were much less effective or entirely inactive.

  基于钯催化的交叉偶联反应，开发出一种简便高效的合成6-(羟甲基)嘌呤衍生物（碱基和核苷）的方法。该方法利用6-卤代嘌呤或N-保护的2-氨基-6-卤代嘌呤与（苯甲氧甲基）锌碘化物进行交叉偶联反应，然后进行去保护。还研究了2,6-二卤代嘌呤的区域选择性羟甲基化反应，并用于合成2-氯-6-(羟甲基)或2,6-双(羟甲基)嘌呤。其中6-(羟甲基)嘌呤核苷5f表现出高的细胞静止效应和适度的腺苷脱氨酶抑制作用，而其他衍生物则效果较弱或完全无效。
• Covalent Analogues of DNA Base-Pairs and Triplets VII. Synthesis and Cytostatic Activity of Bis(purin-6-yl)acetylene and -diacetylene Nucleosides
  作者：Petr Nauš、Ivan Votruba、Michal Hocek

  DOI：10.1135/cccc20041955

  日期：——

  The title bis(purin-6-yl)acetylene and -diacetylene nucleoside derivatives were prepared as covalent base-pair analogues starting from acyl-protected 6-ethynylpurine and 6-iodopurine nucleosides by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by deprotection. The key starting acyl-protected 6-ethynylpurine nucleosides were prepared by a sequence of cross-coupling reactions of protected 6-halopurine nucleosides with (trimethylsilyl)acetylene followed by a modified desilylation with TBAF in presence of acetic acid. Surprisingly, the acyl-protected nucleosides exhibited significant cytostatic activity higher than the fully deprotected title compounds.

  标题为双(嘌呤-6-基)乙炔和-二乙炔核苷衍生物，通过Sonogashira交叉偶联或氧化炔基二聚反应起始于酰保护的6-乙炔基嘌呤和6-碘嘌呤核苷，然后进行去保护作用制备共价碱基对类似物。关键的起始酰保护的6-乙炔基嘌呤核苷是通过保护的6-卤代嘌呤核苷与(三甲基硅基)乙炔的交叉偶联反应序列，然后在存在乙酸的TBAF的修饰去硅化反应中制备的。令人惊讶的是，酰保护的核苷表现出显著的细胞增殖抑制活性，比完全去保护的标题化合物更高。
• A Facile and Efficient Synthesis of (Purin-6-yl)alanines
  作者：Petr Čapek、Radek Pohl、Michal Hocek

  DOI：10.1021/jo048812r

  日期：2004.11.1

  (Purin-6-yl)alanines, a new class of amino acid-nucleobase conjugates, were synthesized by palladium-catalyzed cross-coupling reactions of protected iodozincalanines with 6-iodopurines (9-Bn-6-iodopurine and 9-THP-6-iodopurine as well as acyl-protected 6-iodopurine ribonucleoside and 2-deoxyribonucleoside). Free purine base and nucleosides bearing alanine in position 6 were obtained after complete deprotection of the products of cross-coupling reactions.