N-(9H-purin-6-yl)pivalamide

• 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: N-(9H-purin-6-yl)pivalamide
• 英文别名: 6-N-pivaloyl-adenine；2,2-dimethyl-N-(7H-purin-6-yl)propanamide
• 化学式: C₁₀H₁₃N₅O
• mdl: MFCD20144062
• 分子量: 219.246
• InChiKey: OUPQQNPWKOWOED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(9H-purin-6-yl)pivalamide 生成 N-(7-benzyloxymethyl-7H-purin-6-yl)-2,2-dimethyl-propionamide
  参考文献：
  名称：

  RASMUSSEN M.; CHAN J. H.-S., AUSTRAL. J. CHEM. , 1975, 28, NO 5, 1031-1047

  摘要：

  DOI：
• 作为产物：
  描述：

  腺嘌呤 、 乙醇锂 生成 N-(9H-purin-6-yl)pivalamide
  参考文献：
  名称：

  RASMUSSEN, M.;HOPE, J. M., AUSTRAL. J. CHEM., 1982, 35, N 3, 535-542

  摘要：

  DOI：

文献信息

• Syntheses of 2′-deoxy-2′-fluoro-β-d-arabinofuranosyl purine nucleosides via selective glycosylation reactions of potassium salts of purine derivatives with the glycosyl bromide
  作者：Grigorii G. Sivets

  DOI：10.1016/j.tetlet.2015.11.091

  日期：2016.1

  Syntheses of 9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-guanine (1) and -adenine (2) were accomplished from readily available 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-d-arabinofuranose (3). A new and efficient approach for the synthesis of 1-α-bromide was developed using the mild bromination of α-1-O-benzoate (3). Selective coupling reactions of the bromosugar with purine potassium salts followed by derivatization/and

  9-（2-脱氧-2-氟-β - d-阿拉伯呋喃糖基）-鸟嘌呤（1）和-腺嘌呤（2）的合成是由容易获得的1,3,5-三-O-苯甲酰基-2-脱氧完成的-2-氟-α - d-阿拉伯呋喃糖（3）。利用α-1- O-苯甲酸酯的轻度溴化作用，开发了一种新的高效合成1-α-溴化物的方法（3）。溴糖与嘌呤钾盐的选择性偶联反应，然后对中间体封闭的2'-氟β-阿拉伯糖核苷进行衍生化和/或去保护，导致形成具有高总收率的目标化合物。
• The phosphoramidate ProTide approach greatly enhances the activity of β-2′-C-methylguanosine against hepatitis C virus
  作者：Christopher McGuigan、Plinio Perrone、Karolina Madela、Johan Neyts

  DOI：10.1016/j.bmcl.2009.05.122

  日期：2009.8

  l-alanine phosphoramidate derivatives with variations to the amino acid ester. The 1-naphthyl phosphoramidate of β-2′-methylguanosine containing the benzyl ester (20) was the most active at 0.12 μM, an 84-fold of increase in activity compared to the parent nucleoside (2) with no increase of cytotoxicity. The carboxypeptidase mediated hydrolysis of several ProTides showed a predictive correlation with their

  β-2'-C-甲基嘌呤（1，2）是已知的丙型肝炎病毒（HCV）的抑制剂。我们在此报告了其5'-磷酸氨基甲酸酯ProTides的合成，生物学和酶学评估。本文描述了七个具有氨基酸酯变化的1-丙氨酸氨基磷酸酯衍生物。含苄基酯（20）的β-2'-甲基鸟苷的1-萘基氨基磷酸酯活性最高，为0.12μM，与亲本核苷（2）相比，活性增加了84倍，而细胞毒性没有增加。羧肽酶介导的几种ProTide的水解显示其与复制子中HCV的活性之间的预测相关性。
• [EN] SYNTHESIS OF FLUORINATED NUCLEOTIDES<br/>[FR] SYNTHÈSE DE NUCLÉOTIDES FLUORÉS
  申请人：MERCK SHARP & DOHME

  公开号：WO2022035917A1

  公开（公告）日：2022-02-17

  The present invention relates to efficient processes useful in the preparation of fluorinated nucleosides, such as (O-[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl}O,O-dihydrogen phosphorothioate, also known as 2'-(S)-fluoro-thio-adenosine monophosphate or 2'-F-thio-AMP. Such fluorinated nucleosides may be useful as a biologically active compound and or as an intermediate for the synthesis of more complex biologically active compounds. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

  本发明涉及有效的过程，用于制备氟代核苷，例如（O-[(2R,3R,4S,5R)-5-(6-氨基-9H-嘌呤-9-基)-4-氟-3-羟基氧杂环己烷-2-基]甲基}O，O-二氢磷酸硫酯，也称为2'-(S)-氟硫腺苷酸单磷酸酯或2'-F-硫-AMP。这种氟代核苷可以用作生物活性化合物，或用作更复杂生物活性化合物的合成中间体。本发明还涵盖了在所披露的合成过程中有用的中间体及其制备方法。
• Diverse Catalytic Reactions for the Stereoselective Synthesis of Cyclic Dinucleotide MK-1454
  作者：Tamas Benkovics、Feng Peng、Eric M. Phillips、Chihui An、Rachel S. Bade、Cheol K. Chung、Zachary E. X. Dance、Patrick S. Fier、Jacob H. Forstater、Zhijian Liu、Zhuqing Liu、Peter E. Maligres、Nicholas M. Marshall、Nastaran Salehi Marzijarani、John A. McIntosh、Steven P. Miller、Jeffrey C. Moore、Andrew J. Neel、Jennifer V. Obligacion、Weilan Pan、Michael T. Pirnot、Marc Poirier、Mikhail Reibarkh、Benjamin D. Sherry、Zhiguo Jake Song、Lushi Tan、Ben W. H. Turnbull、Deeptak Verma、Jacob H. Waldman、Lu Wang、Tao Wang、Matthew S. Winston、Feng Xu

  DOI：10.1021/jacs.1c12106

  日期：2022.4.6

  environmental impact. Enzyme-catalyzed reactions have become an impressive and necessary tool that offers benefits such as increased selectivity and waste limitation. These benefits are amplified when enzymatic processes are conducted in a cascade in combination with novel bond-forming strategies. In this article, we report a highly diastereoselective synthesis of MK-1454, a potent agonist of the stimulator

  随着有机化学从业者努力提供最复杂的天然产物和候选药物的有效合成，需要进一步创新合成策略以促进其有效构建。这些雄心勃勃的突破往往伴随着成本和环境影响的大幅降低。酶催化反应已成为一种令人印象深刻且必要的工具，它提供了诸如提高选择性和限制废物等好处。当酶促过程结合新的键形成策略以级联方式进行时，这些好处会被放大。在本文中，我们报告了 MK-1454 的高度非对映选择性合成，MK-1454 是干扰素基因 (STING) 信号通路刺激剂的有效激动剂。合成从两个含氟脱氧核苷酸的不对称构建开始。这些路线旨在实现最大的收敛性和选择性，依赖于相同的良性亲电氟化试剂。从这些复杂的亚基中，四种酶被用于在高度选择性、高产的级联过程中构建两个桥接硫代磷酸盐。该反应成功的关键是彻底了解过渡金属在键形成中的作用。
• [EN] NOVEL FORMS OF CYCLIC DINUCLEOTIDE COMPOUNDS<br/>[FR] NOUVELLES FORMES DE COMPOSÉS DINUCLÉOTIDIQUES CYCLIQUES
  申请人：MERCK SHARP & DOHME LLC

  公开号：WO2022216577A1

  公开（公告）日：2022-10-13

  Novel forms of 2-amino-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5,8-methanofuro[3,2-l][1,3,6,9,11,2,10]pentaoxa-diphosphacyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, which include crystalline salts and hydrates of 2-amino-9-[(2R,5R,7R,8S,10R,12aR, 14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfido-octahydro-12H-5,8-methanofuro[3,2-l][1,3,6,9,11,2,10]pentaoxa-diphosphacyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, may be useful as inductors of type I interferon production, specifically as STING active agents.

  2-氨基-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-氨基-9H-嘌呤-9-基)-15,16-二氟-2,10-二羟基-2,10-二硫酸酯-八氢-12H-5,8-甲氧基呋喃[3,2-l][1,3,6,9,11,2,10]戊二磷环四十二烷-7-基]-1,9-二氢-6H-嘌呤-6-酮的新型形式，包括2-氨基-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-氨基-9H-嘌呤-9-基)-15,16-二氟-2,10-二羟基-2,10-二硫酸酯-八氢-12H-5,8-甲氧基呋喃[3,2-l][1,3,6,9,11,2,10]戊二磷环四十二烷-7-基]-1,9-二氢-6H-嘌呤-6-酮的晶体盐和水合物，可用作I型干扰素产生的诱导剂，特别是作为STING活性剂。