5'-amino-5'-deoxy-2',3'-bis-O-(tert-butyldimethylsilyl)-uridine | 251296-60-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-amino-5'-deoxy-2',3'-bis-O-(tert-butyldimethylsilyl)-uridine
• 英文别名: TBDMS(-2)[TBDMS(-3)]Ribf5N(b)-uracil-1-yl；1-[(2R,3R,4R,5R)-5-(aminomethyl)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 251296-60-3
• 化学式: C₂₁H₄₁N₃O₅Si₂
• 分子量: 471.745
• InChiKey: RFCNJNDUVJWQCA-VDHUWJSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5'-amino-5'-deoxy-2',3'-bis-O-(tert-butyldimethylsilyl)-uridine 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 1-((2R,3R,4S,5R)-5-(((4-(3,4-dihydroxyphenyl)thiazol-2-yl)amino)methyl)-3,4-dihydroxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Inhibition studies on Mycobacterium tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase (GlmU)

  摘要：

  肽聚糖是细菌细胞壁的重要组成部分，包括结核分枝杆菌，它为细胞提供结构强度和刚性，以抵御内部渗透压。肽聚糖生物合成中的第一个关键步骤是尿苷二磷酸-N-乙酰氨基葡萄糖（UDP-GlcNAc）从尿苷三磷酸（UTP）和GlcNAc-1-磷酸形成。此反应由N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶（GlmU）催化，GlmU是一种双功能酶，具有两个独立的活性位点，分别具备乙酰转移酶和尿苷转移酶活性。在此，我们报告了针对结核分枝杆菌GlmU的尿苷转移酶活性的首次抑制研究。最初准备了一些潜在抑制剂，导致发现了活性氨基喹唑啉类化合物。在这一系列中，最有效的抑制剂对GlmU尿苷转移酶活性的IC50为74μM，是发现更高效抑制剂的良好起点。

  DOI：

  10.1039/c3ob41896k
• 作为产物：
  描述：

  5'-azido-5'-deoxyuridine 在 吡啶 、 咪唑 、 1,3-丙二硫醇 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 异丙醇 为溶剂， 生成 5'-amino-5'-deoxy-2',3'-bis-O-(tert-butyldimethylsilyl)-uridine
  参考文献：
  名称：

  甲壳素合酶抑制剂杂芳基-核苷衍生物的设计，合成和生物学评估。

  摘要：

  我们在这里报告了几丁质合酶糖类似物新模型的设计，合成和生物学评估。这些UDP-GlcNAc模拟物将模仿糖的杂芳基和尿苷结合在一起，并与不同的焦磷酸盐生物等排体相连。该化合物对几丁质合酶显示出弱的抑制活性，并且已经针对多种病原真菌对它们的抗真菌效力进行了测定。

  DOI：

  10.1016/s0960-894x(03)00239-7

文献信息

• New monomeric and dimeric uridinyl derivatives as inhibitors of chitin synthase
  作者：Katarzyna Kral、Tadeusz Bieg、Urszula Nawrot、Katarzyna Włodarczyk、Anna Lalik、Przemysław Hahn、Ilona Wandzik

  DOI：10.1016/j.bioorg.2015.05.007

  日期：2015.8

  study described the synthesis and in vitro evaluation of eight new derivatives of uridine as antifungal agents and inhibitors of chitin synthase. Dimeric uridinyl derivatives synthesized by us did not exhibit significant activity. One of the studied monomeric derivative, 5′-(N-succinyl)-5′-amino-5′-deoxyuridine methyl ester (compound 7) showed activities against several fungal strains (MIC range 0.06–1

  这项研究描述了八种新型尿苷衍生物（作为抗真菌剂和几丁质合酶抑制剂）的合成和体外评估。我们合成的二聚尿嘧啶衍生物没有表现出明显的活性。研究的一种单体衍生物5'-（N-琥珀酰基）-5'-氨基-5'-脱氧尿苷甲酯（化合物7）显示出对几种真菌菌株（MIC范围为0.06-1.00 mg / mL）的活性并抑制了几丁质来自酿酒酵母的合酶（IC 50  = 0.8 mM）。此外，化合物7显示出与卡泊芬净对白色念珠菌的协同相互作用（FIC指数＝ 0.28）。
• Design of Glycosyltransferase Inhibitors: Serine Analogues as Pyrophosphate Surrogates?
  作者：Shuai Wang、Jose A. Cuesta-Seijo、Alexander Striebeck、Dominique Lafont、Monica M. Palcic、Sébastien Vidal

  DOI：10.1002/cplu.201500282

  日期：2015.10

  provided modest glycosyltransferase inhibitors. The synthetic strategy employed a combination of glycosylation, amide bond formation and azide-alkyne "click" chemistry. Inhibition constants (Ki ) in the high micromolar range were obtained with a selection of five galactosyltransferases. Cocrystals of three inhibitors bound at the active site of a blood group A/B synthesizing glycosyltransferase were

  用丝氨酸类似物模拟核苷酸二磷酸糖的二磷酸部分提供了适度的糖基转移酶抑制剂。合成策略采用了糖基化，酰胺键形成和叠氮化物-炔烃“点击”化学的组合。通过选择五种半乳糖基转移酶，可获得高微摩尔范围内的抑制常数（Ki）。分析了在合成糖基转移酶的A / B血型的活性位点结合的三种抑制剂的共晶体。类似物的结构和抑制模式证明了酶的灵活性，这使糖基转移酶抑制剂的合理设计复杂化。
• Synthesis of ribonucleic guanidine: replacement of the negative phosphodiester linkages of RNA with positive guanidinium linkages
  作者：Naoshi Kojima、Istvan E Szabo、Thomas C Bruice

  DOI：10.1016/s0040-4020(01)01185-1

  日期：2002.1

  Replacement of the negatively charged phosphodiester linkages of RNA with positively charged guanidinium linkages provides the polycationic ribonucleic guanidine (RNG). RNG is designed to bind strongly to target DNA/RNA through the specific interactions of nucleobases and the attractive electrostatic interactions of backbones, thus RNG is a putative antisense/antigene agent. Preparation of uridine

  用带正电的胍盐键代替RNA的带负电的磷酸二酯键，可提供聚阳离子核糖核酸胍（RNG）。RNG被设计为通过核碱基的特异性相互作用和主链的有吸引力的静电相互作用与目标DNA / RNA牢固结合，因此RNG是推定的反义/抗原试剂。报道了用于RNG合成的尿苷和腺嘌呤结构单元的制备以及低聚RNG的逐步合成。已合成了五聚体同型尿嘧啶基，腺苷酸和五聚体混合碱基序列。该方法还应用于方便的RNG固相合成。
• Synthesis and biological evaluation of 5′-glycyl derivatives of uridine as inhibitors of 1,4-β-galactosyltransferase
  作者：Jadwiga Paszkowska、Katarzyna Kral、Tadeusz Bieg、Karolina Żaba、Katarzyna Węgrzyk、Natalia Jaśkowiak、Antonio Molinaro、Alba Silipo、Ilona Wandzik

  DOI：10.1016/j.bioorg.2014.11.001

  日期：2015.2

  New 5'-glycyl derivatives of uridine containing fragments of varying lipophilicity were synthesized as analogues of natural peptidyl antibiotics. One of the studied compounds, 5'-O-(N-succinylglycyl)-2',3'-O-isopropylideneuridine (A4), showed moderate inhibition against 1,4-beta-galactosyltransferase. However, additional studies showed that the observed inhibitory effect was due to binding to bovine serum albumin, which was used in assays as a stabilizer. (C) 2014 Elsevier Inc. All rights reserved.
• Synthesis and activity of 5′-Uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin A
  作者：Nigel I Howard、Timothy D.H Bugg

  DOI：10.1016/s0968-0896(03)00270-0

  日期：2003.7

  A series of 5'-uridinyl dipeptides were synthesised which mimic the amino terminal chain of nucleoside antibiotic mureido omycin A. Aminoacyl-beta-alanyl- and aminoacyl-N-methyl-beta-alanyl- dipeptides were attached either via an ester linkage to the 5'-hydroxyl of uridine. or via an amide linkage to 5-amino-5-deoxyuridine. The most active inhibitor of Escherichia coli phosphoMurNAc-pentapeptide translocase (MraY) was 5'-O-((L)-Ala-N-methyl-beta-alanyl)-uridine (131), which also showed 97% enzyme inhibition at 2.35mM concentration, and showed antibacterial activity at 100 mug/mL concentration against Pseudomonas putida. Both the central N-methyl amide linkage and a 5' uridine ester linkage were required for highest biological activity. Enzyme inhibition was shown to be competitive with Mg2+. It is proposed that the primary amino terminus of the inhibitor binds in place of the Mg2+. cofactor at the MraY active site, positioned via a cis-N-methyl amide linkage. (C) 2003 Elsevier Science Ltd. All rights reserved.