(+/-)-2-hydroxymethyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione | 191216-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (+/-)-2-hydroxymethyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione
• 英文别名: 5-(Hydroxymethyl)-2-phenyl-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-1,3-dione
• CAS: 191216-18-9
• 化学式: C₁₃H₁₃N₃O₃
• 分子量: 259.265
• InChiKey: GWFNORONKAJXFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-2-hydroxymethyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione 在 四氧化锇 、 一水合肼 、 N-甲基吗啉氧化物 作用下， 以 丙酮 、 叔丁醇 为溶剂， 反应 140.0h， 生成 5-epi-1-azafagomine
  参考文献：
  名称：

  1-Azafagomine: A Hydroxyhexahydropyridazine That Potently Inhibits Enzymatic Glycoside Cleavage

  摘要：

  Abstract(3,4‐trans‐4,5‐trans)‐4,5‐dihydroxy‐3‐hydroxymethylhexahydropyrida‐zine (16) was synthesized in four steps from 2,4‐pentadienol (22) and 4‐phenyl‐triazolin‐3,5‐dione (18) in an overall yield of 32%. In the first step a Diels‐Alder reaction between 18 and 22 gave (π)‐2‐hydroxymethyl‐8‐phenyl‐1,6,8‐triazabicyclo[4.3.0]non‐3‐ene‐7,9‐dione (23c) in 88% yield. Epoxidation of 23c with trifluoromethyl(methyl)dioxirane, generated in situ, gave the trans epoxide 24c in 62% yield. Hydrolysis of the epoxide with perchloric acid gave stereoselectively (2,3‐trans‐3,4‐trans)‐3,4‐dihydroxy‐2‐hydroxy‐methyl‐8‐phenyl‐1,6,8‐triazabicyclo[4.3.0]‐nonane‐7,9‐dione (26) in 73% yield. In the fourth and final step, hydrazinolysis of 26 gave 16 in 84% yield. Pyridazine 16 was found to be a potent inhibitor of α‐and β‐glucosidase, isomaltase and glyco‐gen phosphorylase, while galactosidases and α‐mannosidase were not inhibited. The inhibition of β‐glucosidase is independent of pH, and was found to be due to unprotonated 16.

  DOI：

  10.1002/chem.19970030616
• 作为产物：
  描述：

  4-苯基脲唑 在 次氯酸叔丁酯 作用下， 以 乙酸乙酯 为溶剂， 反应 18.58h， 生成 (+/-)-2-hydroxymethyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione
  参考文献：
  名称：

  1-Azafagomine: A Hydroxyhexahydropyridazine That Potently Inhibits Enzymatic Glycoside Cleavage

  摘要：

  Abstract(3,4‐trans‐4,5‐trans)‐4,5‐dihydroxy‐3‐hydroxymethylhexahydropyrida‐zine (16) was synthesized in four steps from 2,4‐pentadienol (22) and 4‐phenyl‐triazolin‐3,5‐dione (18) in an overall yield of 32%. In the first step a Diels‐Alder reaction between 18 and 22 gave (π)‐2‐hydroxymethyl‐8‐phenyl‐1,6,8‐triazabicyclo[4.3.0]non‐3‐ene‐7,9‐dione (23c) in 88% yield. Epoxidation of 23c with trifluoromethyl(methyl)dioxirane, generated in situ, gave the trans epoxide 24c in 62% yield. Hydrolysis of the epoxide with perchloric acid gave stereoselectively (2,3‐trans‐3,4‐trans)‐3,4‐dihydroxy‐2‐hydroxy‐methyl‐8‐phenyl‐1,6,8‐triazabicyclo[4.3.0]‐nonane‐7,9‐dione (26) in 73% yield. In the fourth and final step, hydrazinolysis of 26 gave 16 in 84% yield. Pyridazine 16 was found to be a potent inhibitor of α‐and β‐glucosidase, isomaltase and glyco‐gen phosphorylase, while galactosidases and α‐mannosidase were not inhibited. The inhibition of β‐glucosidase is independent of pH, and was found to be due to unprotonated 16.

  DOI：

  10.1002/chem.19970030616

文献信息

• Enantiospecific Synthesis of 1-Azafagomine
  作者：Bettina V. Ernholt、Ib B. Thomsen、Anders Lohse、Igor W. Plesner、Kenneth B. Jensen、Rita G. Hazell、Xifu Liang、Astrid Jakobsen、Mikael Bols

  DOI：10.1002/(sici)1521-3765(20000117)6:2<278::aid-chem278>3.0.co;2-6

  日期：2000.1.17

  L-xylose was converted to (-)-1-azafagomine ((-)-1). Enzymatic and other routes to optically pure 1-azafagomine were also studied. Compound (-)-1 is a potent competitive glycosidase inhibitor, while (+)-1 has no biological activity. The inhibition of almond beta-glucosidase by (-)-1 was found to be slow owing to a slow binding step of inhibitor to enzyme, with no subsequent conformational rearrangement

  糖苷酶抑制剂1-azafagomine的两种对映体形式首次从D-和L-木糖开始合成。将D-木糖转化为2,3,5-三苄基呋喃糖，将其与氨基甲酸叔丁酯还原胺化后，可以高收率得到被保护的1-肼基-1-脱氧戊糖醇。N-乙酰化，4-OH的甲磺酸化，Boc基团的去除，环化和脱保护得到（+）-1-azafagomine（（+）-1）。通过类似的反应序列，L-木糖被转化为（-）-1-氮杂花胺（（-）-1）。还研究了通过酶促途径和其他途径获得光学纯的1-氮杂谷氨酰胺。化合物（-）-1是有效的竞争性糖苷酶抑制剂，而（+）-1没有生物活性。由于抑制剂与酶的结合步骤缓慢，因此发现（-）-1对杏仁β-葡萄糖苷酶的抑制作用较慢，没有随后的构象重排。发现结合和释放的速率常数分别为3.3 x 10（4）M（-1）s（-1）和0.011 s（-1），产生Ki = 0.33 microM。
• The First Tri- and Tetraalkoxysilanes with Four Different Substituents
  作者：Rasmus P. Clausen、Mikael Bols

  DOI：10.1021/jo970317q

  日期：1997.6.1

  Unsymmetrically substituted tri- and tetraalkoxysilanes were surprisingly found to be configurationally stable and easy to prepare. It was found that compounds of type MeSi(OR)(2)(OR'), MeSi(OR)(OR')(OR ''), Si(OR)(2)(OR')(2), Si(OR)(2)(OR')(OR ''), Si(OR)(3)(OR'), and even Si(OR)(OR')(OR '')(OR*) could be obtained by sequential addition of a variety of chiral and achiral alcohols to methyltrichlorosilane or tetrachlorosilane in the presence of pyridine. In the case of MeSi(OR)(OR')(OR '') and Si(OR)(OR')(OR '')(OR*), two types of compounds that have never been prepared before, were obtained in good yield.