(S)-2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione | 252268-48-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并哒嗪类
• 英文名称: (S)-2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione
• 英文别名: 5-Hydroxymethyl-2-methyl-5,8-dihydro-[1,2,4]triazolo[1,2-A]pyridazine-1,3-dione；(5S)-5-(hydroxymethyl)-2-methyl-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-1,3-dione
• CAS: 252268-48-7
• 化学式: C₈H₁₁N₃O₃
• 分子量: 197.194
• InChiKey: YXLVIORYJGPOCZ-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (S)-2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione 在 Oxone 、 高氯酸 、 1,1,1-三氟丙酮 、 碳酸氢钠 、 一水合肼 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Enantiopure 1-Azafagomine

  摘要：

  A new chemoenzymatic synthesis of both enantiomeric forms of the glycosidase inhibitor 1-azafagomine (1) is reported. The synthesis starts from the achiral starting materials pentadienol and methylurazol with the key steps being a hetero-Diels-Alder reaction followed by a lipase R/Novozym 435-catalyzed enantioselective esterification of the Diels-Alder adduct.

  DOI：

  10.1021/jo9907989
• 作为产物：
  描述：

  (S)-2-acetoxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以76%的产率得到(S)-2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Enantiopure 1-Azafagomine

  摘要：

  A new chemoenzymatic synthesis of both enantiomeric forms of the glycosidase inhibitor 1-azafagomine (1) is reported. The synthesis starts from the achiral starting materials pentadienol and methylurazol with the key steps being a hetero-Diels-Alder reaction followed by a lipase R/Novozym 435-catalyzed enantioselective esterification of the Diels-Alder adduct.

  DOI：

  10.1021/jo9907989

文献信息

• Synthesis of 1-azagalactofagomine, a potent galactosidase inhibitor
  作者：Henrik Helligsø Jensen、Mikael Bols

  DOI：10.1039/b007973l

  日期：——

  1-Azagalactofagomine [(+)-(3R,4S,5R)-4,5-Dihydroxy-3-(hydroxymethyl)hexahydropyridazine, 2] was synthesised from achiral starting materials in a chemoenzymic synthesis. The racemic Diels–Alder adduct (2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione, 5) from addition of pentadienol to 4-methyl-1,2,4-triazoline-3,5-dione was resolved using lipase R-catalysed acetylation. The acetate [(S)-2-acetoxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione, 6] was saponified and treated with MCPBA to give a majority of the syn epoxide [(2R,3S,4R)-3,4-epoxy-2-hydroxymethyl-8-methyl-1,6,8-triazabicyclo[4.3.0]nonane-7,9-dione, 7]. This isomer was subjected to epoxide opening with HI followed by a Woodward reaction-like displacement of the iodide with water and peracetylation to give an all-syn triacetate [(2R,3S,4R)-3,4-diacetoxy-2-acetoxymethyl-1,6,8-triazabicyclo[4.3.0]nonane-7,9-dione, 11]. Finally deacetylation and hydrazinolysis gave 2. The pKa of 2 was determined to be 5.7. 1-Azagalactofagomine was found to be a potent competitive galactosidase inhibitor. The inhibition constants, Ki, were 40, 300 and 7800 nM versus β-galactosidase from Aspergillusoryzae, Eschinchia coli and Saccharomyces fragilis, respectively, and 280 nM vs. α-galactosidase from green coffee beans.

  1-氮杂半乳糖胺[(+)-(3R,4S,5R)-4,5-二羟基-3-(羟甲基)六氢哒嗪,2]是通过化学酶合成由非手性起始原料合成的。戊二烯醇加成至 4-甲基- 外消旋狄尔斯-阿尔德加合物 (2-羟甲基-8-甲基-1,6,8-三氮杂双环[4.3.0]non-3-烯-7,9-二酮, 5)使用脂肪酶 R 催化的乙酰化拆分 1,2,4-三唑啉-3,5-二酮。将乙酸酯[(S)-2-乙酰氧基甲基-8-甲基-1,6,8-三氮杂双环[4.3.0]壬-3-烯-7,9-二酮, 6]皂化并用MCPBA处理，得到大部分顺式环氧化物 [(2R,3S,4R)-3,4-环氧-2-羟甲基-8-甲基-1,6,8-三氮杂双环[4.3.0]壬烷-7,9-二酮, 7] 。该异构体用 HI 进行环氧化物开环，然后用水进行类似伍德沃德反应的碘化物置换，并进行全乙酰化，得到全顺式三乙酸酯 [(2R,3S,4R)-3,4-二乙酰氧基-2-乙酰氧基甲基- 1,6,8-三氮杂双环[4.3.0]壬烷-7,9-二酮，11]。最后脱乙酰基和肼解得到2。2的pKa测定为5.7。 1-Azagalactofagomine 被发现是一种有效的竞争性半乳糖苷酶抑制剂。抑制常数 Ki 分别为 40、300 和 7800 nM 分别来自米曲霉、大肠杆菌和脆弱酵母的 β-半乳糖苷酶，以及 280 nM 与来自绿咖啡豆的 α-半乳糖苷酶。
• Chemoenzymatic Synthesis of Enantiopure 1-Azafagomine
  作者：Xifu Liang、Mikael Bols

  DOI：10.1021/jo9907989

  日期：1999.11.1

  A new chemoenzymatic synthesis of both enantiomeric forms of the glycosidase inhibitor 1-azafagomine (1) is reported. The synthesis starts from the achiral starting materials pentadienol and methylurazol with the key steps being a hetero-Diels-Alder reaction followed by a lipase R/Novozym 435-catalyzed enantioselective esterification of the Diels-Alder adduct.