benzyl D-glucuronate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl D-glucuronate
• 英文别名: D-glucuronic acid benzyl ester；benzyl (2S,3S,4S,5R)-3,4,5,6-tetrahydroxyoxane-2-carboxylate
• 化学式: C₁₃H₁₆O₇
• 分子量: 284.266
• InChiKey: MYEUFSLWFIOAGY-IHDQXYMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl D-glucuronate 在 palladium on activated charcoal N-甲基吗啉 、 1,4-环己二烯 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 异丙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 (S)-布洛芬葡糖苷酸
  参考文献：
  名称：

  Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate

  摘要：

  Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent beta-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.05.050
• 作为产物：
  描述：

  N,N-二甲基甲酰胺二苄基缩醛 在 盐酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 26.0h， 生成 benzyl D-glucuronate
  参考文献：
  名称：

  由D-葡萄糖醛酸的4-甲氧基苄叉衍生物制备一些苄基D-葡萄糖醛酸酯

  摘要：

   由于在通过酸水解和/或氢解去除亚苄基期间，苄基1,2：3,5-二-O-亚苄基-α - D- 呋喃呋喃糖酸酯中苄基酯键的稳定性低 ，因此4-甲氧基亚苄基用于保护 D- 葡萄糖醛酸的游离羟基 。制备了几种 D- 葡萄糖醛酸的苄基酯 ，并通过反应混合物的液相色谱分离和随后的二极管阵列检测，确定了其酸催化水解的相对速率。

  DOI：

  10.1007/s007060070028

文献信息

• Cyclization of the Acyl Glucuronide Metabolite of a Neutral Endopeptidase Inhibitor to an Electrophilic Glutarimide:  Synthesis, Reactivity, and Mechanistic Analysis
  作者：Xiaoli Meng、James L. Maggs、David C. Pryde、Simon Planken、Rosalind E. Jenkins、Torren M. Peakman、Kevin Beaumont、Christopher Kohl、B. Kevin Park、Andrew V. Stachulski

  DOI：10.1021/jm0706766

  日期：2007.11.1

  unstable thioesters. Imide 4 acylated eight lysine Nepsilon-amino groups of human serum albumin. Rapid cyclization of 3 was attributed to attack on the ester linkage by an unusually nucleophilic glutaramide NH (pKa in 2 = 9.76). N-propyl 3 was refractory to acyl migration and cyclization. This suggested a synthetic strategy for preparing analogues of 2 that form chemically stable acyl glucuronides.

  中性内肽酶抑制剂 (2R)-2-[(1-[(5-ethyl-1,3,4-thiadiazol-2-yl)amino]carbonyl}cyclopentyl)methyl]pen tanoic acid 2 代谢为酰基葡萄糖醛酸3. 前所未有的是，在 pH 7.4 时，3 不经历酰基葡萄糖醛酸苷的 O-酰基迁移特征，而是快速、消除环化（37 摄氏度下的 t1/2，10.2 分钟）为戊二酰亚胺 4。葡萄糖醛酸苷 3 是通过酰化有效合成的带有 N-苄氧基甲基保护的苄基葡萄糖醛酸 2. 葡萄糖醛酸和酰亚胺在 pH 7.4 的水溶液中与氨基酸和谷胱甘肽快速反应，形成稳定的酰胺和不稳定的硫酯。酰亚胺 4 酰化人血清白蛋白的八个赖氨酸 Nepsilon-氨基。3 的快速环化归因于异常亲核的戊二酰胺 NH（2 中的 pKa = 9.76）对酯键的攻击。N-丙基 3 不易发生酰基迁移和环化。这提出了一种用于制备
• Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients
  作者：Thomas G. Hammond、Xiaoli Meng、Rosalind E. Jenkins、James L. Maggs、Anahi Santoyo Castelazo、Sophie L. Regan、Stuart N. L. Bennett、Caroline J. Earnshaw、Guruprasad P. Aithal、Ira Pande、J. Gerry Kenna、Andrew V. Stachulski、B. Kevin Park、Dominic P. Williams

  DOI：10.1124/jpet.114.215079

  日期：2014.8

  Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug - derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug - related hypersensitivities had either a single drug - derived adduct or one of five combinations of 2–8 adducts from among seven diclofenac N- acylations and three AG glycations on seven of the protein’s 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug’s AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association.

  电亲核酰基葡萄糖醛酸（AG）代谢物对蛋白质的共价修饰被假设为某些羧酸药物相关的超敏反应的原因。这些药物AG的复杂重排和反应性已经被详细定义，并且在实验动物和人类的肝脏和血浆中发现了如双氟氯噻吨（diclofenac）等羧酸药物的蛋白质加合物。然而，在缺乏明确的分子特征表征，特别是对保留葡萄糖醛酸和羧基残基的特征糖基化共轭物的鉴定的情况下，无法假定这些加合物的来源唯一或部分来自AG代谢物。因此，我们针对从双氟氯噻吨患者中分离的人血清白蛋白（HSA）进行了靶向质谱分析，以表征药物衍生的结构，从而首次明确解构了药物AG及其异构体重排产物在体内加合物形成的路径。这些分析基于对HSA与双氟氯噻吨AG在体外反应的深入理解。来自六名没有药物相关超敏反应的患者的HSA中，发现了单一的药物衍生加合物或由七种双氟氯噻吨N-酰化和三种AG糖基化中的2-8种加合物的五种组合。其中，只有酰化物在每位患者身上都被发现。我们提供证据表明，双氟氯噻吨在体内对HSA的修饰是复杂多变的，至少部分这些修饰源于该药物的AG代谢物，并且白蛋白加合并不必然导致对羧酸药物的超敏反应，也不是偶然的关联。
• Synthesis, transacylation kinetics and computational chemistry of a set of arylacetic acid 1β-O-acyl glucuronides
  作者：Neil G. Berry、Lisa Iddon、Mazhar Iqbal、Xiaoli Meng、Prabha Jayapal、Caroline H. Johnson、Jeremy K. Nicholson、John C. Lindon、John R. Harding、Ian D. Wilson、Andrew V. Stachulski

  DOI：10.1039/b822777b

  日期：——

  chemistry and modelling study was performed on both the ground states of the AGs and the transition states for acyl migration to search for correlations with the kinetic data and to probe the mechanistic detail of the acyl transfer. An excellent degree of correlation was found between the calculated activation energies and the rates of transacylation. Especially, transition state analysis provided for

  许多广泛使用的非甾体抗炎药（NSAID），例如 布洛芬它们的酰基葡萄糖苷酸（AGs）被广泛代谢，这些AGs的反应性引起了有关药物安全性和毒性的重要问题。为了更好地理解这些代谢物的结构反应性，我们对一组具有不同α取代度的苯乙酸酰基葡糖醛酸苷（AG）进行了合成，结构分析和计算的酰化反应性的详细研究。选择性酰化步骤来制备所有的所需的1-（苯基）乙酰基β-d葡吡喃糖醛酸9，12，13和15为以良好的收率单1β端基异构体。用1测量它们的反应性pH 7.4缓冲液中的1 H NMR光谱：在该系统中，转酰化作用相对于水解作用占优势，同时还测定了AG的1β异构体的半衰期。半衰期从化合物9的20分钟到15小时的23小时不等。缺乏对反应性的任何显着浓度依赖性表明，其主要机理是分子内的。对AG的基态和过渡态进行了新的计算化学和建模研究。酰基迁移以寻找与动力学数据的相关性并探查酰基转移的机理细节。在计算的活化能和转
• A Chemoenzymatic Route to a Class of Sucrose Esters
  作者：Christian Possiel、Alexandra Bäuerle、Jürgen Seibel

  DOI：10.1002/ejoc.201701313

  日期：2017.11.16

  Sucrose esters are the most developed carbohydrate esters and applied in food, cosmetic and pharmaceutical industries. Here we introduce a novel chemoenzymatic pathway for the synthesis of β-D-fructofuranosyl-(2,1)-α-D-uronic acid derivatives, a new class of sucrose esters.

  蔗糖酯是最发达的碳水化合物酯，应用于食品、化妆品和制药行业。在这里，我们介绍了一种新的化学酶促途径，用于合成 β-D-呋喃果糖基-(2,1)-α-D-糖醛酸衍生物，一类新的蔗糖酯。
• [EN] A NEW CLASS OF SUCROSE ESTERS AND A METHOD FOR THEIR PREPARATION<br/>[FR] NOUVELLE CLASSE D'ESTERS DE SACCHAROSE ET PROCÉDÉ DE PRÉPARATION CORRESPONDANT
  申请人：UNIV WUERZBURG J MAXIMILIANS

  公开号：WO2019043069A1

  公开（公告）日：2019-03-07

  The present invention relates to a new class of sucrose esters and a method for their preparation.

  本发明涉及一种新型蔗糖酯类化合物及其制备方法。