3,4',5-tri-[N-(2,3-dihydroxypropyl)-carbamoyl]-resveratrol

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3,4',5-tri-[N-(2,3-dihydroxypropyl)-carbamoyl]-resveratrol
• 英文别名: Resv(MDHP-C)3；[4-[(E)-2-[3,5-bis(2,3-dihydroxypropylcarbamoyloxy)phenyl]ethenyl]phenyl] N-(2,3-dihydroxypropyl)carbamate
• 化学式: C₂₆H₃₃N₃O₁₂
• 分子量: 579.561
• InChiKey: UBVPGIKTPYAUAQ-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  236
• 氢给体数：
  9
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3,4',5-tri-[N-(2,3-dihydroxypropyl)-carbamoyl]-resveratrol 在 盐酸 、 水 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 生成 白藜芦醇
  参考文献：
  名称：

  Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol

  摘要：

  Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted carbamate ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted carbamate moiety is suitable for use in prodrugs of polyphenols.

  DOI：

  10.1021/acs.molpharmaceut.5b00464
• 作为产物：
  描述：

  3,4',5-tri-[N-(2,2-dimethyl-1,3-dioxolane-4-methan)-carbamoyl]-resveratrol 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.5h， 以63%的产率得到3,4',5-tri-[N-(2,3-dihydroxypropyl)-carbamoyl]-resveratrol
  参考文献：
  名称：

  New derivatives of resveratrol

  摘要：

  提供了一类新的白藜芦醇衍生物，与白藜芦醇本身相比，具有有利的理化性质。其特征在于存在三个碳酸酯功能，其中白藜芦醇是氧连接的基团，而氮原子带有赋予分子所需特性的取代基。这些新化合物特别适合作为前药和载体用于作为饮食添加剂或药物组合物中使用的白藜芦醇制剂：它们对氧化降解稳定，允许长的保质期，并在生理条件下具有适当的反应性以再生和输送白藜芦醇。

  公开号：

  EP2774915A1

文献信息

• New derivatives of resveratrol
  申请人：Mattarei, Andrea

  公开号：EP2774915A1

  公开（公告）日：2014-09-10

  A novel class of derivatives of resveratrol is provided which have favourable physico-chemical properties when compared with resveratrol itself. It is characterized by the presence of three carbamate functions, in which resveratrol is the oxygen-linked moiety, while the nitrogen atom carries a substituent conferring desirable characteristics to the molecule. These new compounds are especially suitable as precursors (prodrugs) and vehicles of resveratrol in preparations used as dietary integrators or in pharmaceutical compositions: they are stable towards oxidative degradation allowing for long shelf lifetimes and have suitable reactivity to regenerate and deliver resveratrol under physiological conditions.

  提供了一类新的白藜芦醇衍生物，与白藜芦醇本身相比，具有有利的理化性质。其特征在于存在三个碳酸酯功能，其中白藜芦醇是氧连接的基团，而氮原子带有赋予分子所需特性的取代基。这些新化合物特别适合作为前药和载体用于作为饮食添加剂或药物组合物中使用的白藜芦醇制剂：它们对氧化降解稳定，允许长的保质期，并在生理条件下具有适当的反应性以再生和输送白藜芦醇。
• Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol
  作者：Michele Azzolini、Andrea Mattarei、Martina La Spina、Ester Marotta、Mario Zoratti、Cristina Paradisi、Lucia Biasutto

  DOI：10.1021/acs.molpharmaceut.5b00464

  日期：2015.9.8

  Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted carbamate ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted carbamate moiety is suitable for use in prodrugs of polyphenols.