ethyl C-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)formimidate | 1430730-28-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl C-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)formimidate
• 英文别名: [(2R,3R,4S,5R,6R)-3,4,5-tribenzoyloxy-6-(C-ethoxycarbonimidoyl)oxan-2-yl]methyl benzoate
• CAS: 1430730-28-1
• 化学式: C₃₇H₃₃NO₁₀
• 分子量: 651.67
• InChiKey: GEWLDPFHPUDBBU-HXBJCGEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  48
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  ethyl C-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)formimidate 在 吡啶 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 72.0h， 生成 3-(acetoxymethyl)-5-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-1,2,4-triazole
  参考文献：
  名称：

  C-Glucopyranosyl-1,2,4-triazoles As New Potent Inhibitors of Glycogen Phosphorylase

  摘要：

  Glycogen phosphorylase inhibitors are considered as potential antidiabetic agents. 3-(beta-D-Glucopyranosyl)-5-substituted-1,2,4-triazoles were prepared by acylation of O-perbenzoylated N-1-tosyl-C-beta-D-glucopyranosyl formamidrazone and subsequent removal of the protecting groups. The best inhibitor was 3-(beta-D-glucopyranosyl)-5-(2-naphthyl)-1,2,4-triazole (K-i = 0.41 mu M against rabbit muscle glycogen phosphorylase b).

  DOI：

  10.1021/ml4001529
• 作为产物：
  描述：

  (2R,3R,4R,5S,6S)-2-[(苯甲酰氧基)甲基]-6-氰基四氢-2H-吡喃-3,4,5-三基三苯甲酸酯 在 氢溴酸 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 ethyl C-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)formimidate
  参考文献：
  名称：

  Synthesis of substituted 2-(β-d-glucopyranosyl)-benzimidazoles and their evaluation as inhibitors of glycogen phosphorylase

  摘要：

  Microwave assisted condensation of O-perbenzoylated C-(beta-D-glucopyranosyl) formic acid with 1,2-diaminobenzenes in the presence of triphenylphosphite gave the corresponding O-protected 2-(beta-D-glucopyranosyl)-benzimidazoles in moderate yields. O-Perbenzoylated C-(beta-D-glucopyranosyl) formamide and -thioformamide were transformed into the corresponding ethyl C-(beta-D-glucopyranosyl) formimidate and -thioformimidate, respectively, by Et3O center dot BF4. Treatment of the formimidate with 1,2-diaminobenzenes afforded O-protected 2-(beta-D-glucopyranosyl)-benzimidazoles in good to excellent yields. Similar reaction of the thioformimidate gave these compounds in lower yields. The O-benzoyl protecting groups were removed by the Zemplen protocol. These test compounds were assayed against rabbit muscle glycogen phosphorylase (GP) b, the prototype of liver GP, the rate limiting enzyme of glycogen degradation. The best inhibitors were 2-(beta-D-glucopyranosyl)-4-methyl-benzimidazole (K-i = 2.8 mu M) and 2-(beta-D-glucopyranosyl)- naphtho[2,3-d] imidazole (K-i = 2.1 mu M) exhibiting a similar to 3-4 times stronger binding than the unsubstituted parent compound. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2013.01.011

文献信息

• Synthetic, enzyme kinetic, and protein crystallographic studies of C -β- d -glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase
  作者：Anastassia L. Kantsadi、Éva Bokor、Sándor Kun、George A. Stravodimos、Demetra S.M. Chatzileontiadou、Demetres D. Leonidas、Éva Juhász-Tóth、Andrea Szakács、Gyula Batta、Tibor Docsa、Pál Gergely、László Somsák

  DOI：10.1016/j.ejmech.2016.06.049

  日期：2016.11

  followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors

  Ç -β- d吡喃葡萄糖基吡咯在吡咯，2-的反应制备衍生物，和-吡咯-3-芳ö -peracetylatedβ- d吡喃葡萄糖基三氯乙酰亚胺酯，而2-（β- d得到吡喃葡萄糖基）吲哚通过使O-全苄基化的β- d-吡喃葡萄糖基乙炔与N-甲苯磺酰基-2-碘苯胺交叉偶联，然后自发闭环。通过使C反应，可以得到O-过苯甲酰化的2-（β- d-吡喃葡萄糖基）咪唑的改进合成方法-吡喃葡萄糖基甲酸酯与α-氨基酮。用糖原磷酸化酶（GP）的同工型分析去保护的化合物，以显示吡咯对兔肌肉GPb无活性。咪唑不仅是肌肉酶（a和b），而且是与药理相关的人肝GPa（ 4（5）-苯基的K i分别为156和26 nM，以及- （2-萘基）衍生物）。rmGPb-咪唑配合物的X射线晶体学研究揭示了强结合的结构特征，也可以解释对吡咯衍生物没有抑制作用。
• C-Glucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase
  作者：Éva Bokor、Zsolt Széles、Tibor Docsa、Pál Gergely、László Somsák

  DOI：10.1016/j.carres.2015.12.005

  日期：2016.6

  Various C-glucopyranosyl-1,2,4-triazolones were designed as potential inhibitors of glycogen phosphorylase. Syntheses of these compounds were performed with O-perbenzoylated glucose derivatives as precursors. High temperature ring closure of N(1)-carbamoyl-C-β-D-glucopyranosyl formamidrazone gave 3-β-D-glucopyranosyl-1,2,4-triazol-5-one. Reaction of N(1)-tosyl-C-β-D-glucopyranosyl formamidrazone with

  设计了各种C-吡喃葡萄糖基-1，2，4-三唑酮作为糖原磷酸化酶的潜在抑制剂。这些化合物的合成以邻-过苯甲酰化的葡萄糖衍生物为前体进行。N（1）-氨基甲酰基-C-β-D-吡喃葡萄糖基甲酰胺ami的高温闭环得到3-β-D-吡喃葡萄糖基-1,2,4-三唑-5-酮。N（1）-甲苯磺酰基-C-β-D-吡喃葡萄糖基甲酰胺zone与ClCOOEt的反应提供了3-β-D-吡喃葡萄糖基-1-甲苯磺酰基1,2,4-三唑-5-酮。PhNHNHBoc将原位制备的β-D-吡喃葡萄糖基羰基异氰酸酯转化为3-β-D-吡喃葡萄糖基-1-苯基-1,2,4-三唑-5-酮，而类似的1-（2-萘基）衍生物为萘-2-硼酸在Cu（II）催化的N-芳基化反应中从未取代的三唑酮制得。通过Zemplén脱酰作用制备测试化合物。
• C-(β-d-Glucopyranosyl)formamidrazones, formic acid hydrazides and their transformations into 3-(β-d-glucopyranosyl)-5-substituted-1,2,4-triazoles: a synthetic and computational study
  作者：Éva Bokor、Attila Fekete、Gergely Varga、Béla Szőcs、Katalin Czifrák、István Komáromi、László Somsák

  DOI：10.1016/j.tet.2013.09.099

  日期：2013.12

  Synthesis of O-perbenzoylated 3-(beta-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, precursors of potent inhibitors of glycogen phosphorylase, was studied by ring closures of N-1-acyl-carboxamidrazone type intermediates. Reactions of C-(beta-D-glucopyranosyl)formimidate or C-(beta-D-glucopyranosyl)formamidine with acid hydrazides as well as acylation of C-(beta-D-glucopyranosyl)formamidrazone by acid chlorides unexpectedly gave the corresponding 1,3,4-oxadiazoles instead of 1,2,4-triazoles. The desired triazoles were obtained in reactions of C-(beta-D-glucopyranosyl)formamidine or C-(beta-D-glucopyranosyl) formyl chloride with arenecarboxamidrazones, and also in acylations of N-1-tosyl-C-(beta-D-glucopyranosyl)formamidrazone with acid chlorides. Theoretical calculations (B3LYP and M06-2X OFT with the standard 6-31G(d,p) basis set) on simple model compounds with methyl and phenyl substituents to understand the bifurcation of the ring closure of N-1-acyl-carboxamidrazones indicated that in general the reaction led to 1,2,4-triazoles. However, the probability of the 1,3,4-oxadiazole forming pathway was shown to be significantly higher with N-1-benzoyl-acetamidrazones, which were closest analogues of the intermediates resulting in C-glucosyl-1,3,4-oxadiazoles. It was thereby demonstrated that the substitution pattern of the N-1-acyl-carboxamidrazones played a fundamental role in determining the direction of the ring closing reaction. (C) 2013 Elsevier Ltd. All rights reserved.
• [EN] GLYCOGEN PHOSPHORYLASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHORYLASE DE GLYCOGÈNE
  申请人：DEBRECENI EGYETEM

  公开号：WO2013061105A8

  公开（公告）日：2013-09-19
• Synthesis of substituted 2-(β-d-glucopyranosyl)-benzimidazoles and their evaluation as inhibitors of glycogen phosphorylase
  作者：Éva Bokor、Enikő Szilágyi、Tibor Docsa、Pál Gergely、László Somsák

  DOI：10.1016/j.carres.2013.01.011

  日期：2013.11

  Microwave assisted condensation of O-perbenzoylated C-(beta-D-glucopyranosyl) formic acid with 1,2-diaminobenzenes in the presence of triphenylphosphite gave the corresponding O-protected 2-(beta-D-glucopyranosyl)-benzimidazoles in moderate yields. O-Perbenzoylated C-(beta-D-glucopyranosyl) formamide and -thioformamide were transformed into the corresponding ethyl C-(beta-D-glucopyranosyl) formimidate and -thioformimidate, respectively, by Et3O center dot BF4. Treatment of the formimidate with 1,2-diaminobenzenes afforded O-protected 2-(beta-D-glucopyranosyl)-benzimidazoles in good to excellent yields. Similar reaction of the thioformimidate gave these compounds in lower yields. The O-benzoyl protecting groups were removed by the Zemplen protocol. These test compounds were assayed against rabbit muscle glycogen phosphorylase (GP) b, the prototype of liver GP, the rate limiting enzyme of glycogen degradation. The best inhibitors were 2-(beta-D-glucopyranosyl)-4-methyl-benzimidazole (K-i = 2.8 mu M) and 2-(beta-D-glucopyranosyl)- naphtho[2,3-d] imidazole (K-i = 2.1 mu M) exhibiting a similar to 3-4 times stronger binding than the unsubstituted parent compound. (C) 2013 Elsevier Ltd. All rights reserved.