麦可酚酸-酰基-Β-D-葡糖苷酸 | 99043-04-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 麦可酚酸-酰基-Β-D-葡糖苷酸
• 中文别名: -D-葡糖苷酸；麦可酚酸-酰基-Β；麦可酚酸-酰基-&Beta-D-葡糖苷酸；麦可酚酸-酰基-Β-D -葡糖苷酸
• 英文名称: Mycophenolic acid acyl glucuronide
• 英文别名: mycophenolic acid-O-acyl-β-D-glucopyranuronoside；mycophenolic acid acylglucuronide；(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoyl]oxyoxane-2-carboxylic acid
• CAS: 99043-04-6
• 化学式: C₂₃H₂₈O₁₂
• 分子量: 496.468
• InChiKey: QBMSTEZXAMABFF-UEARNRKISA-N

物化性质

• 熔点：
  94-96°C
• 沸点：
  805.0±65.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  少许溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  189
• 氢给体数：
  5
• 氢受体数：
  12

安全信息

• 储存条件：
  -20°C，干燥，充氩

反应信息

• 作为产物：
  描述：

  霉酚酸 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 麦可酚酸-酰基-Β-D-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

文献信息

• Convenient syntheses of the in vivo carbohydrate metabolites of mycophenolic acid: reactivity of the acyl glucuronide
  作者：Amy E. Jones、Helen K. Wilson、Paul Meath、Xiaoli Meng、David W. Holt、Atholl Johnston、Michael Oellerich、Victor W. Armstrong、Andrew V. Stachulski

  DOI：10.1016/j.tetlet.2009.06.060

  日期：2009.9

  Following in vivo use of mycophenolic acid, the O-aryl and O-acyl glucuronides, as well as the recently discovered O-aryl glucoside (Scheme 1), are all found as metabolites. We describe convenient preparations of all three derivatives. The phenolic glycosides are obtained by phase-transfer-catalysed alkylation of methyl mycophenolate in very high yield, as an excellent alternative to the Königs-Knorr

  在体内使用麦考酚酸后，O-芳基和O-酰基葡糖醛酸苷以及最近发现的O-芳基葡糖苷（方案1）均被发现是代谢产物。我们描述了所有三种衍生物的方便制备方法。酚类糖苷是通过相转移催化的麦考酚酸甲酯烷基化获得的，产率很高，可作为柯尼希斯-克诺尔反应的绝佳替代品。我们仔细优化了早期的酰基葡糖醛酸苷合成方法，从而以更高的收率获得了高纯度的产品。最后，我们描述了合成酰基葡糖醛酸苷在证明其对已知靶蛋白的反应性方面具有对天然获得的物质的优异响应的价值。
• Preparative Enzymatic Synthesis of the Acylglucuronide of Mycophenolic Acid
  作者：Matthias Kittelmann、Urs Rheinegger、Aude Espigat、Lukas Oberer、Reiner Aichholz、Eric Francotte、Oreste Ghisalba

  DOI：10.1002/adsc.200303044

  日期：2003.6

  (3) of mycophenolic acid (1) was enzymatically synthesised on a preparative scale (450 mg substrate) under optimised reaction conditions with 51% conversion. By screening 9 liver homogenates from 8 vertebrate species, it was shown that only with liver homogenate from horse as the catalyst were the acyl- (3) and the O-glucuronide (2) were formed in a ca. 1 : 1 ratio. With homogenates from other sources

  在优化的反应条件下以51％的转化率在制备规模（450 mg底物）上酶促合成了霉酚酸（1）的酰基葡萄糖醛酸（3）。通过筛选8种脊椎动物的9种肝匀浆，发现只有以马的肝匀浆为催化剂，才能在大约3倍的溶液中形成酰基-（3）和O-葡糖醛酸苷（2）。1：1的比例。与其他来源的匀浆一起，产生了过量的O-葡萄糖醛酸（2）。通过优化共底物UDP-葡糖醛酸的浓度和反应温度，可以转化为酰基葡糖醛酸（3）从最初的34％增加到55％，酰基-（3）与O-葡萄糖醛酸苷（2）的比例从1.5：1增加到3.9：1。该反应也可以在酶膜反应器中连续进行，但是转化率较低收率较高，因此消耗的UDP-葡萄糖醛酸比重较高。
• Effective Synthesis of 1β-Acyl Glucuronides by Selective Acylation
  作者：Jennifer A. Perrie、John R. Harding、David W. Holt、Atholl Johnston、Paul Meath、Andrew V. Stachulski

  DOI：10.1021/ol0507165

  日期：2005.6.1

  Acyl glucuronides are vital metabolites for many carboxylic acid containing drugs. We report an efficient new method for the chemical synthesis of these molecules by selective 1 beta-acylation of allyl glucuronate with carboxylic acids catalyzed by HATU and then mild deprotection through treatment with Pd(PPh3)(4) and morpholine. The method is effective for a range of aryl and alkyl carboxylic acids, including important drugs.
• Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate
  作者：Elizabeth R. Bowkett、John R. Harding、James L. Maggs、B. Kevin Park、Jennifer A. Perrie、Andrew V. Stachulski

  DOI：10.1016/j.tet.2007.05.050

  日期：2007.8

  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.