N⁶,N⁶-dibenzoyl-2',3'-O-isopropylideneadenosine 5'-aldehyde | 119244-47-2

• 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: N⁶,N⁶-dibenzoyl-2',3'-O-isopropylideneadenosine 5'-aldehyde
• 英文别名: N-[9-[(3aR,4R,6S,6aS)-6-formyl-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]purin-6-yl]-N-benzoylbenzamide
• CAS: 119244-47-2
• 化学式: C₂₇H₂₃N₅O₆
• 分子量: 513.51
• InChiKey: LIXKHUDBWYSUMA-NWOYTWEOSA-N

物化性质

• 沸点：
  730.8±70.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  38.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  125.74
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N⁶,N⁶-dibenzoyl-2',3'-O-isopropylideneadenosine 5'-aldehyde 在 palladium on activated charcoal 氢气 、 sodium hexamethyldisilazane 、 甲基肼 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， 反应 19.0h， 生成 9-((3aR,4R,6R,6aR)-2,2-Dimethyl-6-phenethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-ylamine
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5'-moieties and are shown to have different k(cat)/K values compared with the natural MTAP substrate (MTA). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.107
• 作为产物：
  描述：

  N⁶,N⁶-di-benzoyl-2',3'-O-isopropylideneadenosine 在 二氯乙酸 、 二甲基亚砜 、 N,N'-二环己基碳二亚胺 作用下， 反应 1.5h， 生成 N⁶,N⁶-dibenzoyl-2',3'-O-isopropylideneadenosine 5'-aldehyde
  参考文献：
  名称：

  同工酶特异性抑制剂的方法。16.L-乙硫氨酸和β，γ-亚氨基-ATP的新型甲基-C5'共价加合物，其为大鼠甲硫氨酸腺苷转移酶的有效多底物抑制剂。

  摘要：

  通过一锅5'-O-三甲基甲硅烷基化，N6-苯甲酰基化和去甲硅烷基化容易地合成的N6，N6-二苯甲酰基-2'，3'-O-异丙基亚氨腺苷被转化为相应的5'-醛。将其用CH 2 ＝ CHMgBr处理，在脱苯甲酰化后，分别得到5′-C-乙烯基-2′，3′-O-异丙基亚氨腺苷的5′S和5′R差向异构体的1∶3混合物。通过对5'R差向异构体的单晶X射线衍射分析来确定构型。混合的差向异构5'-C-乙烯基核苷的5'-O-四氢吡喃基衍生物的氢硼化反应很容易提供5'（S，R）-C-（2-羟乙基）-2'，3'-O-异丙基亚丙基腺苷。用L-高半胱氨酸二钠处理该5'（S，R）-C-（2-O-甲苯磺酰基）衍生物可方便地引入L-乙硫氨酸系统。用较早的合成蛋氨酸-ATP加合物的方法，保护了α-氨基酸，在O5'处引入了β，γ-亚氨基三磷酰基，并去除了保护基，得到标题加合物它的两个5'差向异构体的2：3混合物。它是标题酶的M

  DOI：

  10.1021/jm00124a026

文献信息

• 4'-5'-Unsaturated 5'-halogenated nucleosides. Mechanism-based and competitive inhibitors of S-adenosyl-L-homocysteine hydrolase
  作者：Esa T. Jarvi、James R. McCarthy、Shujaath Mehdi、Donald P. Matthews、Michael L. Edwards、Nellikunja J. Prakash、Terry L. Bowlin、Prasad S. Sunkara、Philippe Bey

  DOI：10.1021/jm00106a028

  日期：1991.2

  an extra chlorine to the 5'-vinyl position (i.e. 51 and 52), modification of the 2'-hydroxyl group to the deoxy (34 and 35) and arabino (36 and 37) nucleosides provided competitive inhibitors of SAH hydrolase. Nucleosides 6 and 13, as well as 5'-deoxy-5',5'-difluoroadenosine (14) proved to be time-dependent inhibitors of SAH hydrolase. All three compounds are postulated to inhibit through the potent

  （E）-和（Z）-5'-氟-4'，5'-二氢-5'-脱氧腺苷（分别为6和13）的设计和合成，这是一类新的基于机理的S-抑制剂描述了腺苷-L-高半胱氨酸（SAH）水解酶。为了确定抑制该酶所必需的结构-活性关系，合成了许多6和13的类似物。用氯代替6（即44）中的氟，在5'-乙烯基位置（即51和52）添加额外的氯，将2'-羟基修饰为脱氧（34和35）和阿拉伯糖（ 36和37）核苷提供了SAH水解酶的竞争性抑制剂。核苷6和13以及5'-脱氧-5'，5'-二氟腺苷（14）被证明是SAH水解酶的时间依赖性抑制剂。假定所有这三种化合物都通过强力亲电试剂来抑制，该亲电试剂是由6或13的3'-羟基氧化成酮（即3和/或E-异构体）而形成的。与提出的通过6、13和14灭活SAH水解酶的机理一致的观察结果是，纯化的大鼠肝脏SAH水解酶与6孵育会释放1当量的氟离子（通过19F NMR），与14孵育会导致释放2当量
• 4',5'-Unsaturated-5'-fluoro adenosine nucleosides: potent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase
  作者：James R. McCarthy、Esa T. Jarvi、Donald P. Matthews、Michael L. Edwards、Nellikunja J. Prakash、Terry L. Bowlin、Shujaath Mehdi、Prasad S. Sunkara、Philippe Bey

  DOI：10.1021/ja00185a052

  日期：1989.2
• Exploration of a potential difluoromethyl-nucleoside substrate with the fluorinase enzyme
  作者：Stephen Thompson、Stephen A. McMahon、James H. Naismith、David O’Hagan

  DOI：10.1016/j.bioorg.2015.11.003

  日期：2016.2

  The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5',5'-Difluoro-5'-deoxyadenosine 7 (F(2)DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5'-fluoro-5'deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F(2)DA 7 was found, however, not to undergo the enzyme catalysed reaction with L-selenomethionine, unlike FDA 2, which undergoes reaction with L-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F(2)DA 7 and tartrate was solved to 1.8 angstrom, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed. (C) 2015 Elsevier Inc. All rights reserved.