(5-Methoxy-2-nitro-phenoxy)-acetic acid methyl ester | 131761-75-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5-Methoxy-2-nitro-phenoxy)-acetic acid methyl ester
• 英文别名: Methyl 2-(5-methoxy-2-nitrophenoxy)acetate
• CAS: 131761-75-6
• 化学式: C₁₀H₁₁NO₆
• 分子量: 241.2
• InChiKey: DGLFGVRQHIGEMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5-Methoxy-2-nitro-phenoxy)-acetic acid methyl ester 在 palladium on activated charcoal sodium tetrahydroborate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以64%的产率得到4-羟基-7-甲氧基-1,4-苯并恶嗪-3-酮
  参考文献：
  名称：

  Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol

  摘要：

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.

  DOI：

  10.1021/jo00005a025
• 作为产物：
  描述：

  3-甲氧基苯酚 在 硝酸 、 potassium carbonate 作用下， 以 溶剂黄146 、 丙酮 为溶剂， 生成 (5-Methoxy-2-nitro-phenoxy)-acetic acid methyl ester
  参考文献：
  名称：

  Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol

  摘要：

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.

  DOI：

  10.1021/jo00005a025

文献信息

• Synthesis and biological evaluation of prodrugs for nitroreductase based 4-β-amino-4′-Demethylepipodophyllotoxin as potential anticancer agents
  作者：Zheng-Rong Wu、Wei Deng、Dian He

  DOI：10.1007/s00044-022-02847-5

  日期：2022.7

  A series of prodrugs for nitroreductase (NTR) based 4-β-amino-4′- Demethylepipodophyllotoxin as potential anticancer agents were synthesized, and their antiproliferative activities in vitro showed compounds 2b (IC50 = 0.77, 0.83 and 1.19 μM) and 2d (IC50 = 0.98, 0.91 and 1.58 μM) were greatly selectively toxic to tumor cells A-549, HeLa and HepG2, respectively, and lower damage to normal WI-38 cells

  合成了一系列基于硝基还原酶 (NTR) 的 4-β-氨基-4'-去甲基表鬼臼毒素作为潜在抗癌剂的前药，其体外抗增殖活性显示化合物2b (IC 50  = 0.77, 0.83 和 1.19 μM) 和2d ( IC 50  = 0.98, 0.91 和 1.58 μM) 分别对肿瘤细胞 A-549、HeLa 和 HepG2 具有极大的选择性毒性，与阳性药物依托泊苷和去甲基表鬼臼毒素相比，对正常 WI-38 细胞的损伤更低，并诱导细胞周期停滞在 G2/M 期，HeLa 细胞中 G1 期的数量随之减少，并伴有细胞凋亡。此外，分子对接模型表明化合物2b和2d似乎与 NTR 1DS7 形成稳定的键。总之，这些缀合物有可能被开发为抗肿瘤药物。
• ATKINSON, JEFFREY;MORAND, PETER;ARNASON, JOHN T.;NIEMEYER, HERMANN M.;BRA+, J. ORG. CHEM., 56,(1991) N, C. 1788-1800
  作者：ATKINSON, JEFFREY、MORAND, PETER、ARNASON, JOHN T.、NIEMEYER, HERMANN M.、BRA+

  DOI：——

  日期：——
• Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol
  作者：Jeffrey Atkinson、Peter Morand、John T. Arnason、Hermann M. Niemeyer、Hector R. Bravo

  DOI：10.1021/jo00005a025

  日期：1991.3

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.