(2E)-1-[2-acetoxy-4,6-dibenzyloxy-3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)]phenyl-3-(4-benzyloxyphenyl)prop-2-en-1-one | 898550-57-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (2E)-1-[2-acetoxy-4,6-dibenzyloxy-3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)]phenyl-3-(4-benzyloxyphenyl)prop-2-en-1-one
• 英文别名: 2'-acetoxy-4,4',6'-tri(benzyloxy)-3'-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)chalcone；[3,5-bis(phenylmethoxy)-2-[(E)-3-(4-phenylmethoxyphenyl)prop-2-enoyl]-6-[(2S,3S,4R,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]phenyl] acetate
• CAS: 898550-57-7
• 化学式: C₇₂H₆₆O₁₁
• 分子量: 1107.31
• InChiKey: RCSPBKQHMBLYLO-MWGRKPGVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.9
• 重原子数：
  83
• 可旋转键数：
  28
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2E)-1-[2-acetoxy-4,6-dibenzyloxy-3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)]phenyl-3-(4-benzyloxyphenyl)prop-2-en-1-one 在 thallium(III) nitrate 、 原甲酸三甲酯 、 sodium hydroxide 作用下， 以 甲醇 、 四氢呋喃 、 水 为溶剂， 反应 28.0h， 以63%的产率得到4′,5,7-tri-O-benzyl-8-(2,3,4,6-tetra-O-benzyl-β-D-glucocopyranosyl)genistein
  参考文献：
  名称：

  Exploiting the Therapeutic Potential of 8-β-d-Glucopyranosylgenistein: Synthesis, Antidiabetic Activity, and Molecular Interaction with Islet Amyloid Polypeptide and Amyloid β-Peptide (1–42)

  摘要：

  8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell sensitivity, insulin secretion, and circulating insulin within 7 days at a dose of 4 (mg/kg bw)/day. Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by thioflavin T fluorescence and atomic force microscopy. Molecular recognition studies with IAPP and Aβ1-42 employing saturation transfer difference (STD) confirmed the same binding mode for both amyloid peptides as suggested by their deduced epitope. Insights into the preferred conformation in the bound state and conformers' geometry resulting from interaction with Aβ1-42 were also given by STD, trNOESY, and MM calculations. These studies strongly support 8-β-d-glucopyranosylgenistein as a promising molecular entity for intervention in amyloid events of both diabetes and the frequently associated Alzheimer's disease.

  DOI：

  10.1021/jm501069h
• 作为产物：
  描述：

  2-乙酰基-3,5-双(苄氧基)苯酚 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 1,4-二氧六环 、 水 、 1,2-二氯乙烷 为溶剂， 反应 30.0h， 生成 (2E)-1-[2-acetoxy-4,6-dibenzyloxy-3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)]phenyl-3-(4-benzyloxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Exploiting the Therapeutic Potential of 8-β-d-Glucopyranosylgenistein: Synthesis, Antidiabetic Activity, and Molecular Interaction with Islet Amyloid Polypeptide and Amyloid β-Peptide (1–42)

  摘要：

  8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell sensitivity, insulin secretion, and circulating insulin within 7 days at a dose of 4 (mg/kg bw)/day. Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by thioflavin T fluorescence and atomic force microscopy. Molecular recognition studies with IAPP and Aβ1-42 employing saturation transfer difference (STD) confirmed the same binding mode for both amyloid peptides as suggested by their deduced epitope. Insights into the preferred conformation in the bound state and conformers' geometry resulting from interaction with Aβ1-42 were also given by STD, trNOESY, and MM calculations. These studies strongly support 8-β-d-glucopyranosylgenistein as a promising molecular entity for intervention in amyloid events of both diabetes and the frequently associated Alzheimer's disease.

  DOI：

  10.1021/jm501069h

文献信息

• NEW C-GLYCOSYLPOLYPHENOL ANTIDIABETIC AGENTS, EFFECT ON GLUCOSE TOLERANCE AND INTERACTION WITH BETA-AMYLOID. THERAPEUTIC APPLICATIONS OF THE SYNTHESIZED AGENT(S) AND OF GENISTA TENERA ETHYL ACETATE EXTRACTS CONTAINING SOME OF THOSE AGENTS
  申请人：UNIVERSIDADE DE LISBOA

  公开号：US20150031639A1

  公开（公告）日：2015-01-29

  The present invention concerns the antidiabetic-activity of compounds type A, namely of 8-β-D-glucosylgenistein, which is not toxic to eukaryotic cells and has demonstrated to produce complete normalization of fasting hyperglycaemia, to reduce excessive postprandial glucose excursion, to increase glucose-induced insulin secretion and insulin sensitivity. An alternative synthesis for this molecular entity and its binding ability to β-amyloid oligomers is also included in the present invention, which also comprises Genista tenera ethyl acetate extract for use as antihyperglycaemic, agent i.e. for lowering blood glucose levels in mammals that are pre-diabetic or have type 2 or type 1 diabetes. The inhibitory activity of α-glucosidase by Genista tenera ethyl acetate and butanol extracts and that of glucose-6-phosphatase by these two extracts and the diethyl ether plant extract is also part of the present invention.

  本发明涉及A型化合物的抗糖尿病活性，即8-β-D-葡萄糖基异黄酮的抗糖尿病活性。该化合物对真核细胞无毒，并已证明能完全正常化空腹高血糖，减少过度餐后血糖波动，增加葡萄糖诱导的胰岛素分泌和胰岛素敏感性。本发明还包括该分子实体的另一种合成方法以及其与β-淀粉样寡聚体的结合能力，同时还包括Genista tenera乙酸乙酯提取物用作抗高血糖剂，即用于降低处于糖尿病前期或已患2型或1型糖尿病的哺乳动物的血糖水平。本发明还包括Genista tenera乙酸乙酯和丁醇提取物的α-葡萄糖苷酶抑制活性以及这两种提取物和乙醚植物提取物的葡萄糖-6-磷酸酶抑制活性。
• Total synthesis of two isoflavone C-glycosides: genistein and orobol 8-C-β-d-glucopyranosides
  作者：Shingo Sato、Kaoru Hiroe、Toshihiro Kumazawa、Onodera Jun-ichi

  DOI：10.1016/j.carres.2006.03.038

  日期：2006.7

  Genistein and orobol 8-C-beta-D-glucopyranosides (1 and 3) were firstly synthesized in overall yields of 39% and 41% from 2,4-di-O-benzylphloroacetophenone (4), as follows: (1) the formation of the chalcone (6, 7) by aldol condensation of the benzyl-protected C-glycosylphloroacetophenone (5), a key intermediate of the total synthesis of I and 3 and synthesized by a C-glycosylation method involving the O -> C glycoside rearrangement of 4 in 96% yield; (2) the formation of isoflavones (10, 11 and 12, 13) by the formation of acetals by oxidative rearrangement of the protected chalcones (8 and 9) using TI(NO3)(3), followed by acid-catalyzed cyclization: (3) a final debenzylation by hydrogenolysis. (c) 2006 Elsevier Ltd. All rights reserved.
• US9775856B2
  申请人：——

  公开号：US9775856B2

  公开（公告）日：2017-10-03