5'-azido-N²-isobutyryl-2',3'-O-isopropylidene-5'-deoxyguanosine | 1611476-57-3

• 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: 5'-azido-N²-isobutyryl-2',3'-O-isopropylidene-5'-deoxyguanosine
• 英文别名: N-[9-[(3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 1611476-57-3
• 化学式: C₁₇H₂₂N₈O₅
• 分子量: 418.412
• InChiKey: TYNHWUIDIGXMGR-ORXWAGORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-azido-N²-isobutyryl-2',3'-O-isopropylidene-5'-deoxyguanosine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以82%的产率得到N²-isobutyryl-5'-azidoguanosine
  参考文献：
  名称：

  5'-四氯邻苯二甲酰亚胺和5'-叠氮基5'-脱氧核糖核苷的合成及抗菌活性

  摘要：

  摘要 报道了腺苷和尿苷基 5'-四氯邻苯二甲酰亚胺-5'-脱氧核糖核苷和鸟苷酰 5'-叠氮基-5'-脱氧核糖核苷的有效合成，可用于固相合成氨基磷酸酯和核糖核胍寡核苷酸。通过腺苷和尿苷的光信反应，用四氯邻苯二甲酰亚胺基团取代 5'-羟基。另一种方法用于鸟苷，用叠氮基取代 5'-羟基。将所得化合物转化为 5'-氨基-5'-脱氧核糖核苷用于寡核苷酸合成。合成中间体被测试为针对六种细菌菌株的抗微生物剂。所有含有 2',3'-O-异丙基保护基团的类似物均显示出对脑膜炎奈瑟菌的抗菌活性，

  DOI：

  10.1080/15257770.2016.1250906
• 作为产物：
  描述：

  2',3'-O-异丙亚基鸟苷 在 吡啶 、 三甲基氯硅烷 、 叠氮磷酸二苯酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 生成 5'-azido-N²-isobutyryl-2',3'-O-isopropylidene-5'-deoxyguanosine
  参考文献：
  名称：

  Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with Diguanylate Cyclase

  摘要：

  Cyclic di-GMP (c-di-GMP) is a widespread second messenger that plays a key role in bacterial biofilm formation. The compound's ability to assume multiple conformations allows it to interact with a diverse set of target macromolecules. Here, we analyzed the binding mode of c-di-GMP to the allosteric inhibitory site (I-site) of diguanylate cyclases (DGCs) and compared it to the conformation adopted in the catalytic site of the EAL phosphodiesterases (PDEs). An array of novel molecules has been designed and synthesized by simplifying the native c-di-GMP structure and replacing the charged phosphodiester backbone with an isosteric nonhydrolyzable 1,2,3-triazole moiety. We developed the first neutral small molecule able to selectively target DGCs discriminating between the I-site of DGCs and the active site of PDEs; this molecule represents a novel tool for mechanistic studies, particularly on those proteins bearing both DGC and PDE modules, and for future optimization studies to target DGCs in vivo.

  DOI：

  10.1021/acs.jmedchem.5b01184

文献信息

• A Tractable and Efficient One-Pot Synthesis of 5'-Azido-5'-deoxyribonucleosides
  作者：Theodore Peterson、Tobin Streamland、Ahmed Awad

  DOI：10.3390/molecules19022434

  日期：——

  Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine, guanosine, and uridine, resulting in a widely applicable one-pot methodology for the synthesis of these and related compounds. The target compounds are appropriate as precursors in a variety of purposive syntheses, as the synthetic and therapeutic relevance of azido- and amino-modified nucleosides is expansive. Furthermore

  报道了腺苷、胞苷、鸟苷和尿苷的 5'-叠氮核糖核苷的合成路线，从而为合成这些和相关化合物提供了一种广泛适用的一锅法。目标化合物适合作为各种有目的的合成中的前体，因为叠氮基和氨基修饰的核苷的合成和治疗相关性是广泛的。此外，在将醇转化为叠氮化物的过程中，这些方法为 Mitsunobu 和其他更困难的反应提供了一种易于处理的替代方法。
• Oligonucleotide Analogues with Integrated Bases and Backbone. Part 32
  作者：Martina Schulze-Adams、Bruno Bernet、David Touboul、Daniel Egli、Lorenz Herdeis、Andrea Vasella

  DOI：10.1002/hlca.201400175

  日期：2014.9

  G‐quadruplexes. The quadruplex formation of 7 and 16 was established by 1H‐NMR spectroscopy (only of 16), vapour pressure osmometry, mass spectrometry, and CD spectroscopy. The C(6(I))‐hydroxymethylated analogue 9 in CDCl3 and the fully deprotected dinucleosides 10 and 11 in H2O form only weakly ππ stacked associates, but no G‐quadruplexes, as evidenced by CD spectroscopy.

  G [ s ] G二核苷6和G [ s ] G *二核苷8是通过分别从2和5衍生的鸟苷硫醇的烷基化（由从醇3获得的C（8）-氯甲基化的鸟苷4 ）制备的。。将二核苷6和8分别去酰基化为7和9，并完全脱保护为10和11。G [ n ] G二核苷16通过醛的还原胺化获得13带有膦亚胺从叠氮化物衍生的14和所得到的二聚体脱保护15。在的固态6，并在溶液6和8在CDCl 3，H  N（1 / I）和H  N（1 / II）从事分子内氢键来的所述CO异丁保护基团，和异丁酰基单元的HN我形成interresidue，分子内氢键，以N（7 / II），从而导致顺式核碱基的取向在单元I，到TG硫烷基部分的方向，以及与核碱基的正交方向，以防止任何碱基配对。甲硅烷基化和异亚丙基化的二核苷7和9以溶剂化的单重形式存在于DMSO溶液中。CHCl 3溶液中核苷7和16的1 H-NMR宽信号证明平衡了G-四链体。通过1
• Oligonucleotide Analogues with Integrated Bases and Backbone (ONIB). Part 31
  作者：Martina Schulze-Adams、David Touboul、Bruno Bernet、Andrea Vasella

  DOI：10.1002/hlca.201400156

  日期：2014.8

  The self‐complementary guanosine‐ and cytidine‐derived aminomethylene‐linked C*[n]G dinucleoside 9 was synthesized by reductive amination of aldehyde 3 with an iminophosphorane derived from azide 7. Deacylation of 9 gave the isopropylidene‐protected dinucleoside 10. The sequence‐isomeric G*[n]C dinucleoside 11 was similarly prepared from aldehyde 8 and azide 5, and deacylated to 12. The association

  自互补鸟嘌呤和胞苷衍生的氨基亚甲基连接的C * [ n ] G二核苷9是通过用叠氮化物7衍生的亚氨基磷烷对醛3进行还原胺化而合成的。9的脱酰得到异丙基保护的二核苷10。类似地，由醛8和叠氮化物5制备了序列异构的G * [ n ] C二核苷11，并脱酰为12。CHCl 3或CHCl 3中10和12的缔合/ DMSO混合物和缔合物的结构通过1 H-NMR，ESI-MS，CD和蒸气压渗透压（VPO）进行了研究。宽1二核苷的H-NMR的信号10和12证据双链体和四链之间的平衡（Hoogsteen碱基基地之间配对沃森克里克碱基配对的双链体）。在-50°和室温之间，G * [ n ] C二核苷12的四链体占主导地位。序列异构体C * [ n ] G 10在CDCl 3和CDCl 3 /（D 6中，大部分仅形成环状双链体。DMSO 9：1。
• Synthesis and antibacterial activity of 5′-tetrachlorophthalimido and 5′-azido 5′-deoxyribonucleosides
  作者：Robert Van Ostrand、Casey Jacobsen、Alicia Delahunty、Carley Stringer、Ryan Noorbehesht、Haidi Ahmed、Ahmed M. Awad

  DOI：10.1080/15257770.2016.1250906

  日期：2017.3.4

  ABSTRACT Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative

  摘要 报道了腺苷和尿苷基 5'-四氯邻苯二甲酰亚胺-5'-脱氧核糖核苷和鸟苷酰 5'-叠氮基-5'-脱氧核糖核苷的有效合成，可用于固相合成氨基磷酸酯和核糖核胍寡核苷酸。通过腺苷和尿苷的光信反应，用四氯邻苯二甲酰亚胺基团取代 5'-羟基。另一种方法用于鸟苷，用叠氮基取代 5'-羟基。将所得化合物转化为 5'-氨基-5'-脱氧核糖核苷用于寡核苷酸合成。合成中间体被测试为针对六种细菌菌株的抗微生物剂。所有含有 2',3'-O-异丙基保护基团的类似物均显示出对脑膜炎奈瑟菌的抗菌活性，
• Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with Diguanylate Cyclase
  作者：Silvia Fernicola、Ilaria Torquati、Alessandro Paiardini、Giorgio Giardina、Giordano Rampioni、Marco Messina、Livia Leoni、Fabio Del Bello、Riccardo Petrelli、Serena Rinaldo、Loredana Cappellacci、Francesca Cutruzzolà

  DOI：10.1021/acs.jmedchem.5b01184

  日期：2015.10.22

  Cyclic di-GMP (c-di-GMP) is a widespread second messenger that plays a key role in bacterial biofilm formation. The compound's ability to assume multiple conformations allows it to interact with a diverse set of target macromolecules. Here, we analyzed the binding mode of c-di-GMP to the allosteric inhibitory site (I-site) of diguanylate cyclases (DGCs) and compared it to the conformation adopted in the catalytic site of the EAL phosphodiesterases (PDEs). An array of novel molecules has been designed and synthesized by simplifying the native c-di-GMP structure and replacing the charged phosphodiester backbone with an isosteric nonhydrolyzable 1,2,3-triazole moiety. We developed the first neutral small molecule able to selectively target DGCs discriminating between the I-site of DGCs and the active site of PDEs; this molecule represents a novel tool for mechanistic studies, particularly on those proteins bearing both DGC and PDE modules, and for future optimization studies to target DGCs in vivo.