(2R,3R,4S)-3-acetamido-4-acetoxy-2-((1S,2R)-1,2,3-triacetoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid | 25875-96-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3R,4S)-3-acetamido-4-acetoxy-2-((1S,2R)-1,2,3-triacetoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid
• 英文别名: (2R,3R,4S)-3-acetamido-4-acetyloxy-2-[(1S,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
• CAS: 25875-96-1
• 化学式: C₁₉H₂₅NO₁₂
• 分子量: 459.407
• InChiKey: NGTSUGWLKFJIBY-CZIOMAOESA-N

物化性质

• 沸点：
  615.0±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  181
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S)-3-acetamido-4-acetoxy-2-((1S,2R)-1,2,3-triacetoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid 在 sodium tetrahydroborate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  New Potent Sialyltransferase Inhibitors—Synthesis of Donor and of Transition-State Analogues of Sialyl Donor CMP-Neu5Ac

  摘要：

  Enzymatic sialyl transfer with CMP-Neu5Ac as donor can be inhibited by CDP. Therefore phosphonates 1a,b, 2 and 3 were synthesized as substrate analogues. With alpha(2-6)-sialyltransferase from rat liver (EC2.4.99.1) only moderate inhibition was found for these compounds. In order to obtain transition-state analogues of CMP-Neu5Ac different linkages between 2,3-dehydro-N-acetylneuraminol and CMP were generated, yielding 4, (R)-5 and (R)-6. Compound (R)-6, in which the CMP residue is attached to C-1 of 2,3-dehydro-N-acetylneuramin-1-yl phosphonate, exhibited excellent alpha(2-6)-sialyltransferase inhibition in the nanomolar range (K-i=350 nM), resulting in a 130-fold higher affinity for the enzyme than CMP-Neu5Ac (K-M = 46 mu M).

  DOI：

  10.1002/(sici)1521-3765(19980615)4:6<1106::aid-chem1106>3.0.co;2-7
• 作为产物：
  描述：

  (2S,4S,5R,6R)-benzyl 5-acetamido-2,4-dihydroxy-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-1-carboxylate 在 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 palladium 10% on activated carbon 、 氢气 作用下， 以 吡啶 、 乙醇 、 乙腈 为溶剂， 反应 26.67h， 生成 (2R,3R,4S)-3-acetamido-4-acetoxy-2-((1S,2R)-1,2,3-triacetoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors

  摘要：

  In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC50 value of 0.013, 0.001, and 0.09 mu M against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC50 = 0.0014 mu M, H5N1 IC50 = 0.012 mu M, H1N1 IC50 = 0.001 mu M). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t(1/2)) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.

  DOI：

  10.1021/jm3009713

文献信息

• ２−デオキシ−２，３−ジデヒドロシアル酸誘導体およびその製造法
  申请人：国立大学法人富山大学

  公开号：JP2015117233A

  公开（公告）日：2015-06-25

  【課題】Ｃ−１位に構造多様性を持たせたシアル酸誘導体及びクリック反応によるその製造方法。【解決手段】式［１］で表される２−デオキシ２，３−デヒドロシアル酸誘導体（Ｒ１はチオカルボキシル基、チオアミド基、アシルスルホンアミド基又はスルホニルアミジン基）【選択図】図２

  将其翻译成中文，直接给您结果。【问题】具有C-1位结构多样性的唾液酸衍生物及其制备方法通过点击反应。【解决方案】表示为式[1]的2-去氧-2,3-脱氢唾液酸衍生物（R1为硫代羧基、硫代酰胺基、酰基磺酰胺基或磺酰胺基）【选择图】图2
• A glycal-based photoaffinity probe that enriches sialic acid binding proteins
  作者：Peter S. Thuy-Boun、Dennis W. Wolan

  DOI：10.1016/j.bmcl.2019.07.054

  日期：2019.9

  identify sialic acid binding proteins from complex proteomes, three photocrosslinking affinity-based probes were constructed using Neu5Ac (5 and 6) and Neu5Ac2en (7) scaffolds. Kinetic inhibition assays and Western blotting revealed the Neu5Ac2en-based 7 to be an effective probe for the labeling of a purified gut microbial sialidase (BDI_2946) and a purified human sialic acid binding protein (hCD33)

  为了从复杂的蛋白质组中鉴定唾液酸结合蛋白，使用Neu5Ac（5和6）和Neu5Ac2en（7）支架构建了三个基于光交联亲和力的探针。动力学抑制分析和蛋白质印迹表明，基于Neu5Ac2en的7是标记纯化的肠道微生物唾液酸酶（BDI_2946）和纯化的人类唾液酸结合蛋白（hCD33）的有效探针。此外，基于LC-MS / MS亲和力的蛋白质谱分析证实了7能够从人血清中富集低丰度唾液酸结合蛋白（补体因子H）的能力，从而在复杂的情况下验证了该探针的实用性。
• Furuhata, Kimio; Anazawa, Katsuko; Itoh, Masayoshi, Chemical and pharmaceutical bulletin, 1986, vol. 34, # 7, p. 2725 - 2731
  作者：Furuhata, Kimio、Anazawa, Katsuko、Itoh, Masayoshi、Shitori, Yoshiyasu、Ogura, Haruo

  DOI：——

  日期：——