8,9,10-三羟基-7-(羟基甲基)-2-硫代-6-氧杂-1,3-二氮杂螺[4.5]癸烷-4-酮 | 227458-60-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 8,9,10-三羟基-7-(羟基甲基)-2-硫代-6-氧杂-1,3-二氮杂螺[4.5]癸烷-4-酮
• 英文名称: (2R,3S,4S,5R,6S)-3,4,5-trihydroxy-2-hydroxymethyl-7,9-diaza-1-oxa-spiro[4,5]decane-10-one-8-thione
• 英文别名: glucopyranosylidene-spiro-thiohydantoin；glucopyranosylidene spirothiohydantoin；8,9,10-Trihydroxy-7-hydroxymethyl-2-thioxo-6-oxa-1,3-diaza-spiro[4.5]decan-4-one；(5S,7R,8S,9S,10R)-8,9,10-trihydroxy-7-(hydroxymethyl)-2-sulfanylidene-6-oxa-1,3-diazaspiro[4.5]decan-4-one
• CAS: 227458-60-8
• 化学式: C₈H₁₂N₂O₆S
• 分子量: 264.259
• InChiKey: OEWLGQKSTDZKFN-WWHASAIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  163
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  acarbose 、 8,9,10-三羟基-7-(羟基甲基)-2-硫代-6-氧杂-1,3-二氮杂螺[4.5]癸烷-4-酮 在 Bacillus stearothemophilus maltogenic amylase (EC 3.2.1.133) 、 sodium citrate 作用下， 以 水 为溶剂， 反应 48.0h， 以20%的产率得到α-acarviosinyl-(1->4)-α-D-glucopyranosylidene-spiro-thiohydantoin
  参考文献：
  名称：

  Enzymatic synthesis of a new inhibitor of α-amylases: acarviosinyl-isomaltosyl-spiro-thiohydantoin

  摘要：

  Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%, has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA is capable of transferring the acarviosine-glucose residue from an acarbose donor onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC and MALDI-TOF MS. (1H and 13C NMR studies revealed that the enzyme reserved its stereoselectivity. Glycosylation took place mainly at C-6 resulting in a-acarviosinyl-(14)-a-D-glucopyranosyl-(16)-D-glucopyranosylidene-spiro-thiohydantoin. This compound was found to be a much more efficient salivary amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic constants of K)(EI) (= 0.19 mM and K)(ESI) = 0.24 mM. 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2005.03.003
• 作为产物：
  描述：

  (2R,3R,4S,5R,6R)-2-[(苯甲酰氧基)甲基]-6-氨基甲酰四氢-2H-吡喃-3,4,5-三基三苯甲酸酯 在 甲醇 、 溴 、 sodium methylate 、 sulfur 、 barium carbonate 作用下， 以 四氯化碳 、 硝基甲烷 为溶剂， 反应 11.0h， 生成 8,9,10-三羟基-7-(羟基甲基)-2-硫代-6-氧杂-1,3-二氮杂螺[4.5]癸烷-4-酮
  参考文献：
  名称：

  一种新的可扩展制备的吡喃葡萄糖亚基-螺硫代乙内酰脲：糖原磷酸化酶的最佳抑制剂之一

  摘要：

  在硝基甲烷中，氰化汞（II）将苯溴-葡萄糖转化为过邻苯甲酰化的β-d-吡喃葡萄糖基氰化物。用溴化氢在乙酸中腈的部分水解得到过-O-苯甲酰化的C-（β-d-吡喃葡萄糖基）甲酰胺。使用溴在四氯化碳，氯仿或二氯甲烷中进行光溴化，得到相应的过-O-苯甲酰化的1-溴-1-脱氧-β-d-吡喃葡萄糖基氰化物和C-（1-溴-1-脱氧-β-d-吡喃葡萄糖基）甲酰胺 后者与硫氰酸铵在硝基甲烷中的反应得到过-O-苯甲酰化的C- 6S构型的吡喃吡喃基亚烷基-螺-硫代乙内酰脲，以及少量的O-苯甲酰化的C-（1-羟基-β-d-吡喃葡萄糖基）甲酰胺。在甲醇中用甲醇钠对螺硫代乙内酰脲进行脱苯甲酰化，得到克量的标题抑制剂。所描述的序列应适合于按比例放大，并且可以从d-葡萄糖开始以约30％的总收率制备目标化合物。

  DOI：

  10.1016/s0957-4166(00)00107-5

文献信息

• Gram-scale synthesis of a glucopyranosylidene-spiro-thiohydantoin and its effect on hepatic glycogen metabolism studied in vitro and in vivo
  作者：László Somsák、Veronika Nagy、Tibor Docsa、Béla Tóth、Pál Gergely

  DOI：10.1016/s0957-4166(99)00486-3

  日期：2000.2

  A high yielding, simple synthesis is described starting from D-glucose to produce gram quantities of a glucopyranosylidene-spiro-thiohydantoin. This compound efficiently inhibited the activity of rat liver glycogen phosphorylase a; moreover, it also activated phosphorylase phosphatase which, in turn, decreased the amount of glycogen phosphorylase a. Both effects result in the inhibition of glycogen mobilization and the formation of glucose from glycogen. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis of and a Comparative Study on the Inhibition of Muscle and Liver Glycogen Phosphorylases by Epimeric Pairs of <scp>d</scp>-Gluco- and <scp>d</scp>-Xylopyranosylidene-spiro-(thio)hydantoins and <i>N</i>-(<scp>d</scp>-Glucopyranosyl) Amides
  作者：László Somsák、László Kovács、Marietta Tóth、Erzsébet Ősz、László Szilágyi、Zoltán Györgydeák、Zoltán Dinya、Tibor Docsa、Béla Tóth、Pál Gergely

  DOI：10.1021/jm010892t

  日期：2001.8.1

  D-Gluco- and D-xylopyranosylidene-spiro-hydantoins and -thiohydantoins were prepared from the parent sugars in a six-step, highly chemo-, regio-, and stereoselective procedure. In the key step of the syntheses C-(1-bromo-1-deoxy-beta -D-glycopyranosyl)formamides were reacted with cyanate ion to give spiro-hydantoins with a retained configuration at the anomeric center as the major products. On the other hand, thiocyanate ions gave spiro-thiohydantoins with an inverted anomeric carbon as the only products. On the basis of radical inhibition studies, a mechanistic rationale was proposed to explain this unique stereoselectivity and the formation of C-(1-hydroxy-beta -D-glycopyranosyl)formamides as byproducts. Enzyme assays with a and b forms of muscle and liver glycogen phosphorylases showed spiro-hydantoin 12 and spiro-thiohydantoin 14 to be the best and equipotent inhibitors with K-i values in the low micromolar range. The study of epimeric pairs of D-gluco and D-Xylo configurated spiro-hydantoins and N-(D-glucopyranosyl)amides corroborated the role of specific hydrogen bridges in binding the inhibitors to the enzyme.
• Efficient inhibition of muscle and liver glycogen phosphorylases by a new glucopyranosylidene-spiro-thiohydantoin
  作者：Erzsébet Ősz、László Somsák、László Szilágyi、László Kovács、Tibor Docsa、Béla Tóth、Pál Gergely

  DOI：10.1016/s0960-894x(99)00192-4

  日期：1999.5

  Reaction of C-(1-bromo-1-deoxy-beta-D-glucopyranosyl)forma 2 with thiocyanate ions was the key step of a short synthesis of D-glucopyranosylidene-spiro-thiohydantoin 7 which proved to be a potent inhibitor of muscle and liver glycogen phosphorylases. (C) 1999 Elsevier Science Ltd. All rights reserved.
• A new, scalable preparation of a glucopyranosylidene-spiro-thiohydantoin: one of the best inhibitors of glycogen phosphorylases
  作者：László Somsák、Veronika Nagy

  DOI：10.1016/s0957-4166(00)00107-5

  日期：2000.5

  per-O-benzoylated β-d-glucopyranosyl cyanide by mercury(II) cyanide in nitromethane. Partial hydrolysis of the nitrile with hydrogen bromide in acetic acid gave per-O-benzoylated C-(β-d-glucopyranosyl)formamide. Photobromination using bromine in carbon tetrachloride, chloroform, or dichloromethane gave the corresponding per-O-benzoylated 1-bromo-1-deoxy-β-d-glucopyranosyl cyanide and C-(1-bromo-1-deoxy-β-d-

  在硝基甲烷中，氰化汞（II）将苯溴-葡萄糖转化为过邻苯甲酰化的β-d-吡喃葡萄糖基氰化物。用溴化氢在乙酸中腈的部分水解得到过-O-苯甲酰化的C-（β-d-吡喃葡萄糖基）甲酰胺。使用溴在四氯化碳，氯仿或二氯甲烷中进行光溴化，得到相应的过-O-苯甲酰化的1-溴-1-脱氧-β-d-吡喃葡萄糖基氰化物和C-（1-溴-1-脱氧-β-d-吡喃葡萄糖基）甲酰胺 后者与硫氰酸铵在硝基甲烷中的反应得到过-O-苯甲酰化的C- 6S构型的吡喃吡喃基亚烷基-螺-硫代乙内酰脲，以及少量的O-苯甲酰化的C-（1-羟基-β-d-吡喃葡萄糖基）甲酰胺。在甲醇中用甲醇钠对螺硫代乙内酰脲进行脱苯甲酰化，得到克量的标题抑制剂。所描述的序列应适合于按比例放大，并且可以从d-葡萄糖开始以约30％的总收率制备目标化合物。
• Enzymatic synthesis of a new inhibitor of α-amylases: acarviosinyl-isomaltosyl-spiro-thiohydantoin
  作者：Lili Kandra、Judit Remenyik、Gyula Batta、László Somsák、Gyöngyi Gyémánt、Kwan Hwa Park

  DOI：10.1016/j.carres.2005.03.003

  日期：2005.5

  Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%, has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA is capable of transferring the acarviosine-glucose residue from an acarbose donor onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC and MALDI-TOF MS. (1H and 13C NMR studies revealed that the enzyme reserved its stereoselectivity. Glycosylation took place mainly at C-6 resulting in a-acarviosinyl-(14)-a-D-glucopyranosyl-(16)-D-glucopyranosylidene-spiro-thiohydantoin. This compound was found to be a much more efficient salivary amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic constants of K)(EI) (= 0.19 mM and K)(ESI) = 0.24 mM. 2005 Elsevier Ltd. All rights reserved.