1-((1S,2S,3R,4R,5S)-2,3-dihydroxy-4-(hydroxymethyl)bicyclo[3.1.0]hexan-1-yl)pyramidine-2,4(1H,3H)-dione | 1186507-14-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 1-((1S,2S,3R,4R,5S)-2,3-dihydroxy-4-(hydroxymethyl)bicyclo[3.1.0]hexan-1-yl)pyramidine-2,4(1H,3H)-dione
• 英文别名: 1-[(1S,2S,5S,3R,4R)-2,3-dihydroxy-4-(hydroxymethyl)bicyclo[3.1.0]hexyl]-1,3-dihydropyrimidine-2,4-dione；(S)-methanocarbauridine
• CAS: 1186507-14-1
• 化学式: C₁₁H₁₄N₂O₅
• 分子量: 254.243
• InChiKey: NPGQNFMTZVWTKW-UVWAWMSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  115.55
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-((1S,2S,3R,4R,5S)-2,3-dihydroxy-4-(hydroxymethyl)bicyclo[3.1.0]hexan-1-yl)pyramidine-2,4(1H,3H)-dione 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 、 tri-n-butylamine pyrophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.34h， 生成 (S)-methanocarba-UTP
  参考文献：
  名称：

  Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y₆ Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications

  摘要：

  The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes.

  DOI：

  10.1021/jm100287t
• 作为产物：
  描述：

  在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以72 %的产率得到1-((1S,2S,3R,4R,5S)-2,3-dihydroxy-4-(hydroxymethyl)bicyclo[3.1.0]hexan-1-yl)pyramidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  锁在南构象中的对映体纯嘧啶核糖核苷的合成

  摘要：

  核苷中央五元环的构象在酶识别中起着重要作用。双环 [3.1.0] 己烷，也称为甲烷碳 (MC)，作为模板可以模拟两种独特构象的锁定形式，即南北构象。虽然已积极研究锁定在北方构象中的修饰核苷，但南方对应物在很大程度上仍未开发，因为它难以合成。在此，我们报告了一条简明的合成路线，该路线可以提供以 100% 立体选择性方式合成 ( S )-MC 核糖核苷所必需的关键氨基糖中间体。此外，通过提出的合成方法，我们报告了对映体纯 ( S )-MC 胞苷的首次合成1 . 我们相信我们的发现将极大地促进核苷化学领域，并为发现新的核苷提供机会。

  DOI：

  10.1021/acs.orglett.2c03853