5-amino-1-[2',3',5'-O-tris(tert-butyldimethylsilyl)-β-D-ribofuranosyl]imidazole-4-carboxamide | 300853-86-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 5-amino-1-[2',3',5'-O-tris(tert-butyldimethylsilyl)-β-D-ribofuranosyl]imidazole-4-carboxamide
• 英文别名: 5-amino-1-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]imidazole-4-carboxamide
• CAS: 300853-86-5
• 化学式: C₂₇H₅₆N₄O₅Si₃
• 分子量: 601.022
• InChiKey: BBYDIALHOPGHDU-UMCMBGNQSA-N

物化性质

• 沸点：
  604.2±55.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.26
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-amino-1-[2',3',5'-O-tris(tert-butyldimethylsilyl)-β-D-ribofuranosyl]imidazole-4-carboxamide 在 氟化铵 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 32.0h， 生成 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  仙女化学物质的咪唑类和核糖体咪唑-4-羧酰胺，作为其在水稻中的代谢物。

  摘要：

  咪唑-4-羧酰胺（ICA）在植物中的代谢是未知的。从ICA处理的大米中分离出两种代谢物（1和2），并通过光谱分析（包括单晶X射线衍射技术和合成方法）确定了它们的结构。还可以通过LC-MS / MS从处理过的水稻中合成并检测到ICA的核糖核苷酸（3），并对其进行了检测。这些结果表明大米可能会相互转化ICA，1和3，从而调节其生物活性。

  DOI：

  10.1021/acs.orglett.9b02833
• 作为产物：
  描述：

  2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine 在 potassium carbonate 、 乙二胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 5-amino-1-[2',3',5'-O-tris(tert-butyldimethylsilyl)-β-D-ribofuranosyl]imidazole-4-carboxamide
  参考文献：
  名称：

  Efficient Ribosomal Peptidyl Transfer Critically Relies on the Presence of the Ribose 2‘-OH at A2451 of 23S rRNA

  摘要：

  The ribosomal peptidyl transferase center is a ribozyme catalyzing peptide bond synthesis in all organisms. We applied a novel modified nucleoside interference approach to identify functional groups at 9 universally conserved active site residues. Owing to their immediate proximity to the chemical center, the 23S rRNA nucleosides A2451, U2506 and U2585 were of particular interest. Our study ruled out U2506 and U2585 as contributors of vital chemical groups for transpeptidation. In contrast the ribose 2'-OH of A2451 was identified as the prime ribosomal group with potential functional importance. This 2'-OH renders almost full catalytic power to the ribosome even when embedded into an active site of six neighboring 2'-deoxyribose nucleosides. These data highlight the unique functional role of the A2451 2'-OH for peptide bond synthesis among all other functional groups at the ribosomal peptidyl transferase active site.

  DOI：

  10.1021/ja0588454

文献信息

• Mechanistic studies in the synthesis of a series of thieno-expanded xanthosine and guanosine nucleosides
  作者：Zhibo Zhang、Orrette R. Wauchope、Katherine L. Seley-Radtke

  DOI：10.1016/j.tet.2008.09.011

  日期：2008.11

  During the synthetic pursuit of guanosine (triG) and xanthosine (triX) tricyclic nucleosides analogues, an interesting side product was discovered. In an effort to uncover the mechanistic factors leading to this result, a series of reaction conditions were investigated. It was found that by varying the conditions, the appearance of the side product could be controlled. In addition, the yield of the

  在鸟苷 (triG) 和黄苷 (triX) 三环核苷类似物的合成过程中，发现了一种有趣的副产物。为了揭示导致这一结果的机械因素，研究了一系列反应条件。发现通过改变条件，可以控制副产物的出现。此外，可以控制所需产物的产量，以提供 triG 和 triX 的 50:50 混合，或其中一种或另一种的大部分。为了证明该方法的广泛实用性，它还适用于从 5-氨基-1-β-D-呋喃核糖基-4-咪唑甲酰胺 (AICAR) 合成鸟苷和黄苷。本文报告了围绕合成工作的机制细节。
• Investigations into specificity of azepinomycin for inhibition of guanase: Discrimination between the natural heterocyclic inhibitor and its synthetic nucleoside analogues
  作者：Saibal Chakraborty、Niti H. Shah、James C. Fishbein、Ramachandra S. Hosmane

  DOI：10.1016/j.bmcl.2012.09.053

  日期：2012.12

  an important enzyme of purine salvage pathway of nucleic acid metabolism, it became necessary to investigate if the nucleoside analogues of the heterocycle azepinomycin, which are likely to be formed in vivo, would be more or less potent than the parent heterocycle. To this end, we have resynthesized both azepinomycin (1) and its two diastereomeric nucleoside analogues (2 and 3), employing a modified

  在我们探索天然产物 azepinomycin 及其类似物抑制胍酶（核酸代谢的嘌呤补救途径的重要酶）的构效关系的长期而广泛的计划中，有必要研究杂环 azepinomycin 的核苷类似物是否可能在体内形成，比母体杂环或多或少有效。为此，我们重新合成了 azepinomycin ( 1 ) 及其两个非对映体核苷类似物 ( 2和3))，采用改进的、更有效的程序，并针对哺乳动物鸟苷酸酶对所有三种化合物进行了生化筛选。我们的结果表明，与核苷类似物相比，天然产物抑制胍酶的效力至少是其核苷类似物的 200 倍，观察到的阿西平霉素 ( 1 ) 对兔肝胍酶的K i = 2.5 (±0.6) × 10 -6 M，而化合物2的K i  = 1.19 (±0.02) × 10 -4 M和化合物3的K i =  1.29 (±0.03) × 10 -4 M。还需要注意的是，虽然 IC 50   Azepinomycin
• GMP Synthetase: Synthesis and Biological Evaluation of a Stable Analog of the Proposed AMP-XMP Reaction Intermediate
  作者：Edward J. Salaski、Hans Maag

  DOI：10.1055/s-1999-3104

  日期：——

  The enzyme guanosine monophosphate synthetase is part of the de novo purine synthesis pathway and is responsible for the conversion of xanthosine monophosphate to guanosine monophosphate. The phosphate-linked adenyl-XMP 1 has been proposed as the intermediate in a stepwise mechanism for this conversion. Direct observation of 1; either as produced in the enzymatic reaction, or as a potential synthetic target is not readily feasible due to the high lability of the phosphate linkage. We therefore undertook the synthesis of the phosphonate 2 as a stable analog of this proposed intermediate. The successful synthetic strategy involved the coupling under Mitsunobu conditions of a 2-phosphorylmethyl inosine with an adenosine derivative. This gave 2 after deprotection and 5′ monophosphate formation of the initial coupling product. Compound 2 inhibited GMP synthetase with a Ki of 0.56 μM.

  酶鸟苷酸合成酶是新生嘌呤合成途径的一部分，负责将黄苷酸单磷酸转化为鸟苷酸单磷酸。已提出磷酸链接的腺苷-XMP 1是这一转化过程的中间体。然而，由于磷酸链接的高不稳定性，直接观察1（无论是在酶反应中产生的或作为潜在合成目标）并不容易。因此，我们进行了磷酸酯2的合成，作为这一提议中间体的稳定类似物。成功的合成策略涉及将2-磷酸甲基肌苷与腺苷衍生物在Mitsunobu反应条件下偶联。经过去保护和初始偶联产物的5′单磷酸形成后得到了化合物2。化合物2以0.56 μM的Ki值抑制了GMP合成酶。
• <i>S</i>-Adenosylhomocysteine Analogue of a Fairy Chemical, Imidazole-4-carboxamide, as its Metabolite in Rice and Yeast and Synthetic Investigations of Related Compounds
  作者：Hitoshi Ouchi、Takuya Namiki、Kenji Iwamoto、Nobuo Matsuzaki、Makoto Inai、Mihaya Kotajima、Jing Wu、Jae-Hoon Choi、Yoko Kimura、Hirofumi Hirai、Xiaonan Xie、Hirokazu Kawagishi、Toshiyuki Kan

  DOI：10.1021/acs.jnatprod.0c01269

  日期：2021.2.26

  S-ICAr-H (8a), as a metabolite of imidazole-4-carboxamide (ICA) in rice and yeast (Saccharomyces cerevisiae). In order to determine its absolute configuration, an efficient synthetic method of 8a was developed. This synthetic strategy was applicable to the preparation of analogues of 8a that might be biologically very important, such as S-ICAr-M (9), S-AICAr-H (10), and S-AICAr-M (11).

  在我们对神奇化学品 (FC) 的研究过程中，我们发现了S -ICAr-H ( 8a )，它是水稻和酵母 ( Saccharomyces cerevisiae )中咪唑-4-甲酰胺 (ICA) 的代谢物。为了确定其绝对构型，开发了一种有效的8a合成方法。这种合成策略适用于制备可能在生物学上非常重要的8a类似物，例如S -ICAr-M ( 9 )、S -AICAr-H ( 10 ) 和S -AICAr-M ( 11 )。
• Synthesis of a Cyclic Dinucleotide Analogue with Ambiguous Bases, 5-Aminoimidazole-4-carboxamide
  作者：Noriko S. Tarashima、Yusuke Kumanomido、Katsuyuki Nakashima、Yoshiyuki Tanaka、Noriaki Minakawa

  DOI：10.1021/acs.joc.1c01706

  日期：2021.11.5

  Cyclic dinucleotides (CDNs) are second messengers composed of two purine nucleotides. In recent years, the structural diversity of CDNs and their functionality in biological processes are being intensely studied. Herein we report the chemical synthesis of cyclic di-5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl monophosphate (c-di-ZMP) (1), which consists of two 5-amino-4-imidazolecarboxamide ribonucleotides

  环状二核苷酸 (CDN) 是由两个嘌呤核苷酸组成的第二信使。近年来，CDN的结构多样性及其在生物过程中的功能正在被深入研究。在此，我们报道了环状二-5-氨基咪唑-4-甲酰胺-1-β- d-呋喃核糖基单磷酸盐 (c-di-ZMP) ( 1 ) 的化学合成，它由两个 5-氨基-4-咪唑甲酰胺核糖核苷酸 ( Z-核糖核苷酸）通过两个磷酸二酯键连接。通过亚磷酰胺化学构建具有N 1 -二硝基苯基次黄嘌呤碱基 (Hxa DNP -base) 的 CDN 骨架，随后 Hxa DNP -base 的开环反应成功地产生了所需的1.