萘普生葡糖苷酸 | 41945-43-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 萘普生葡糖苷酸
• 英文名称: (+)-Naproxen glucuronide
• 英文别名: 1-O-[(S)-2-(6-methoxy-2-naphthyl)propionyl]-β-D-glucopyranuronic acid；(S)-naproxen 1-β-O-acyl glucuronide；(S)-naproxen acyl β-D-glucuronide；S-naproxen β-1-O-acyl glucuronide；S-naproxen β-1-O-acyl-glucuronide；(S)-naproxen-β-D-glucuronide；Naproxen Glucuronide；(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(2S)-2-(6-methoxynaphthalen-2-yl)propanoyl]oxyoxane-2-carboxylic acid
• CAS: 41945-43-1
• 化学式: C₂₀H₂₂O₉
• 分子量: 406.389
• InChiKey: XRHIELLXTVJOKM-ODXKUVGNSA-N

物化性质

• 熔点：
  80-82°C
• 沸点：
  642.5±55.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  萘普生葡糖苷酸 在 potassium dihydrogen orthophosphate buffer 作用下， 反应 24.0h， 生成 S-naproxen α-1-O-acyl glucuronide 、 (2S,3S,4R,5R)-4,5,6-Trihydroxy-3-[(S)-2-(6-methoxy-naphthalen-2-yl)-propionyloxy]-tetrahydro-pyran-2-carboxylic acid 、 (2S,3S,4S,5R)-3,4,6-Trihydroxy-5-[(S)-2-(6-methoxy-naphthalen-2-yl)-propionyloxy]-tetrahydro-pyran-2-carboxylic acid 、 (2S,3S,4S,5R)-3,5,6-Trihydroxy-4-[(S)-2-(6-methoxy-naphthalen-2-yl)-propionyloxy]-tetrahydro-pyran-2-carboxylic acid
  参考文献：
  名称：

  HPLC / 1H NMR光谱研究在S-萘普生β-1-O-酰基葡糖醛酸苷的酰基迁移过程中形成的反应性α-1-O-酰基异构体。

  摘要：

  在药物代谢和药代动力学研究中广泛持有的观点是，药物酯葡糖醛酸苷的分子内酰基迁移中最初的1-异构体到2-异构体步骤是不可逆的，并且在生理条件下不会发生α-1-O-酰基异构体。我们使用直接连接质子核磁共振波谱（HPLC / 1H NMR）和质谱（LC / MS）的高效液相色谱法研究了这一假设，以探测S-萘普生β-1-O-酰基葡糖醛酸的迁移反应，在pH 7.4的磷酸盐缓冲液中，温度为37摄氏度。我们报告了通过直接的相应纯净氨基酸的轻松酰基迁移而在生物系统中形成的药物酯葡糖苷酸（S-萘普生）的α-1-O-酰基异构体的首次直接观察。 β-1-O-酰基葡糖醛酸苷。使用停止流一维HPLC / 1H NMR和二维1H-1H总相关光谱法（1H-1H TOCSY）可以明确鉴定反应产物。平行LC /离子阱质谱法得到了确认的葡糖醛酸化物质量。此外，“动态”停止流HPLC / 1H NMR实验表明，分离出的α-1-

  DOI：

  10.1021/tx010015q
• 作为产物：
  描述：

  萘普生 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 萘普生葡糖苷酸
  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

• Synthesis of 1-β-O-acyl glucuronides of diclofenac, mefenamic acid and (S)-naproxen by the chemo-selective enzymatic removal of protecting groups from the corresponding methyl acetyl derivatives
  作者：Akiko Baba、Tadao Yoshioka

  DOI：10.1039/b608755h

  日期：——

  three non-steroidal anti-inflammatory drugs, diclofenac (DF) 5, mefenamic acid (MF) 6 and (S)-naproxen (NP) 7, were prepared. Caesium salts of these carboxylic acid drugs reacted with commercially available methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-alpha-D-glucopyranuronate 4 to give exclusively the corresponding 1-beta-O-acyl glucuronides 8-10 in moderate yields. The protecting acetyl (for -OH group)

  使用简单的化学酶促程序，三种非甾体类抗炎药双氯芬酸（DF）5，甲芬那酸（MF）6和（S）-萘普生（NP）7的1-β-O-酰基葡萄糖醛酸苷分别为准备好了。这些羧酸药物的铯盐与市售的2,3,4-三-O-乙酰基-1-溴-1-脱氧-α-D-吡喃葡萄糖酸酯4反应，仅得到相应的1-β-O-酰基葡糖苷酸8-10的产量中等。容易除去每个糖部分的保护性乙酰基（对于-OH基而言）和甲酯基（对于-CO 2 H基而言），从而以高收率提供了相应的游离的1-β-O-酰基葡糖醛酸内酯1-3。通过使用脂肪酶AS Amano（LAS）对乙酰基进行有效的酶催化化学选择性水解，以及使用来自猪肝的酯酶（PLE）对甲酯基进行有效的酶催化化学选择性水解，可以实现脱保护。
• Synthesis of Urine Drug Metabolites: Glucuronosyl Esters of Carboxymefloquine, Indoprofen, (<i>S</i>)‐Naproxen, and Desmethyl (<i>S</i>)‐Naproxen
  作者：Martina Lahmann、Moa Andresen Bergström、Dominika Turek、Stefan Oscarson

  DOI：10.1081/car-120034003

  日期：2004.12.26

  A general procedure for the synthesis of 1-O-acyl-beta-D-glucuronic acids using the benzyl 1-O-trichloroacetimidoyl-2,3,4-tri-O-benzyl-D-glucopyranuronate 6 as donor is exemplified by the synthesis of the urine metabolites of (S)-naproxen, desmethyl (S)-naproxen, indoprofen, and carboxymefloquine. The key intermediate benzyl 2,3,4-tri-O-benzyl-D-glucopyranuronate 5 is easily accessible in four steps (29%) from the peracetylated beta-D-glucuronic acid 1.
• 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.
• HPLC/¹H NMR Spectroscopic Studies of the Reactive <i>α</i>-1-<i>O</i>-acyl Isomer Formed during Acyl Migration of S-Naproxen <i>β</i>-1-<i>O</i>-acyl Glucuronide
  作者：Olivia Corcoran、Rasmus W. Mortensen、Steen H. Hansen、Jeff Troke、Jeremy K. Nicholson

  DOI：10.1021/tx010015q

  日期：2001.10.1

  first direct observation of the alpha-1-O-acyl isomer of a drug ester glucuronide (S-naproxen) formed in a biosystem via the facile acyl migration of the corresponding pure beta-1-O-acyl glucuronide. The unequivocal identification of the reactive product was achieved using stopped-flow one-dimensional HPLC/1H NMR and two-dimensional 1H-1H total correlation spectroscopy (1H-1H TOCSY). Parallel LC/ion-trap

  在药物代谢和药代动力学研究中广泛持有的观点是，药物酯葡糖醛酸苷的分子内酰基迁移中最初的1-异构体到2-异构体步骤是不可逆的，并且在生理条件下不会发生α-1-O-酰基异构体。我们使用直接连接质子核磁共振波谱（HPLC / 1H NMR）和质谱（LC / MS）的高效液相色谱法研究了这一假设，以探测S-萘普生β-1-O-酰基葡糖醛酸的迁移反应，在pH 7.4的磷酸盐缓冲液中，温度为37摄氏度。我们报告了通过直接的相应纯净氨基酸的轻松酰基迁移而在生物系统中形成的药物酯葡糖苷酸（S-萘普生）的α-1-O-酰基异构体的首次直接观察。 β-1-O-酰基葡糖醛酸苷。使用停止流一维HPLC / 1H NMR和二维1H-1H总相关光谱法（1H-1H TOCSY）可以明确鉴定反应产物。平行LC /离子阱质谱法得到了确认的葡糖醛酸化物质量。此外，“动态”停止流HPLC / 1H NMR实验表明，分离出的α-1-