methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate | 1357156-40-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate
• CAS: 1357156-40-1
• 化学式: C₂₀H₂₁F₂NO₁₂
• 分子量: 505.383
• InChiKey: XLCORMPWXPPKKE-RXBWTVHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  35.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166.8
• 氢给体数：
  0.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate 在 甲醇 、 palladium 10% on activated carbon 、 potassium trimethylsilonate 、 氢气 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.08h， 生成
  参考文献：
  名称：

  An Activity-Based Near-Infrared Glucuronide Trapping Probe for Imaging β-Glucuronidase Expression in Deep Tissues

  摘要：

  beta-glucuronidase is an attractive reporter and prodrug-converting enzyme. The development of near-IR (NIR) probes for imaging of beta-glucuronidase activity would be ideal to allow estimation of reporter expression and for personalized glucuronide prodrug cancer therapy in preclinical studies. However, NIR glucuronide probes are not yet available. In this work, we developed two fluorescent probes for detection of beta-glucuronidase activity, one for the NIR range (containing IR-820 dye) and the other for the visible range [containing fluorescein isothiocyanate (FITC)], by utilizing a difluoromethylphenol-glucuronide moiety (TrapG) to trap the fluorochromes in the vicinity of the active enzyme. beta-glucuronidase-mediated hydrolysis of the glucuronyl bond of TrapG generates a highly reactive alkylating group that facilitates the attachment of the fluorochrome to nucleophilic moieties located near beta-glucuronidase-expressing sites. FITC-TrapG was selectively trapped on purified beta-glucuronidase or beta-glucuronidase-expressing CT26 cells (CT26/m beta G) but not on bovine serum albumin or non-beta-glucuronidase-expressing CT26 cells used as controls. beta-glucuronidase-activated FITC-TrapG did not interfere with beta-glucuronidase activity and could label bystander proteins near beta-glucuronidase. Both FITC-TrapG and NIR-TrapG specifically imaged subcutaneous CT26/m beta G tumors, but only NIR-TrapG could image CT26/m beta G tumors transplanted deep in the liver. Thus NIR-TrapG may provide a valuable tool for visualizing beta-glucuronidase activity in vivo.

  DOI：

  10.1021/ja209335z
• 作为产物：
  描述：

  5-硝基水杨醛 在 二乙胺基三氟化硫 、 silver(l) oxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 12.0h， 生成 methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate
  参考文献：
  名称：

  Development of a Gd(III)-Based Receptor-Induced Magnetization Enhancement (RIME) Contrast Agent for β-Glucuronidase Activity Profiling

  摘要：

  beta-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor induced magnetization enhancement (pro RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FP beta Gu)]) for molecular imaging of beta-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a beta-glucuronidase substrate (beta-D-glucopyranuronic acid). The binding association constant (K-A) of [Gd(DOTA-FP beta Gu)] is 7.42 X 10(2), which is significantly lower than that of a commercially available MS-325 (K-A = 3.0 x 10(4)) RIME contrast agent. The low K-A value of [Gd(DOTA-FP beta Gu)] is due to the pendant beta-D-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FP beta Gu)] can be used for detection of beta-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FP beta Gu)] was elucidated by LC-MS. The kinetics of beta-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FP beta Gu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with K-m = 1.38 mM, K-cat = 3.76 x 10(3), and k(cat)/K-m = 2.72 x 10(3) M-1 s(-1). The low K-m value indicates high affinity of beta-glucuronidase for [Gd(DOTA-FP beta Gu)] FP beta Gu) at physiological pH. Relaxometric studies revealed that T-1 relaxivity of [Gd(DOTA-FP beta Gu)] changes in response to the concentration of beta-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FP beta Gu)] showed significant change in MR image signal in the presence of beta-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of beta-glucuronidase.[GRAPHICS].

  DOI：

  10.1021/ic301827p