3,4-dihydroxy-5-fluorobenzoic acid | 87932-48-7

• 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: 3,4-dihydroxy-5-fluorobenzoic acid
• 英文别名: 5-Fluoro-protocatechuic acid；3-fluoro-4,5-dihydroxybenzoic acid
• CAS: 87932-48-7
• 化学式: C₇H₅FO₄
• 分子量: 172.113
• InChiKey: RTYDIWLGIZQTKB-UHFFFAOYSA-N

物化性质

• 沸点：
  389.7±42.0 °C(Predicted)
• 密度：
  1.670±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-dihydroxy-5-fluorobenzoic acid 在 氯化亚砜 、 硫酸 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 4.33h， 生成 (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-1-carboxy-1-methyl-ethoxyimino]-acetylamino}-3-{[(3,4-diacetoxy-5-fluoro-benzoyl)-ethyl-amino]-methyl}-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model

  摘要：

  Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta-half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2, = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pK(a) values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pK(a) was sufficiently acidic.

  DOI：

  10.1021/jm00092a015
• 作为产物：
  描述：

  3-氟邻苯二酚 、 potassium hydrogencarbonate 在 3,4-dihydroxybenzoic acid decarboxylasesfrom Enterobacter cloacae 作用下， 以 aq. phosphate buffer 为溶剂， 反应 41.0h， 以10.8%的产率得到3,4-dihydroxy-5-fluorobenzoic acid
  参考文献：
  名称：

  使用异戊二烯化黄素依赖性脱羧酶对儿茶酚进行区域选择性对位羧化。

  摘要：

  利用二氧化碳作为有机合成的碳源满足了化学品生产更加可持续性的迫切需求。在此，我们报告了酶催化儿茶酚的对位羧化，使用属于 UbiD 酶家族的 3,4-二羟基苯甲酸脱羧酶 (AroY)。晶体结构和随附的溶液数据证实，AroY 利用最近发现的异戊二烯化 FMN (prFMN) 辅因子，并且需要氧化成熟才能形成具有催化能力的 prFMNiminium 物质。本研究报告了 prFMN 依赖性酶的体外重建和激活，该酶能够在环境条件下直接羧化芳香族儿茶酚底物。提出了一种涉及醌型加合物和辅因子之间具有单共价键的中间体的可逆脱羧反应机制，该机制不同于相关酶中与 prFMN 相关的 1,3-偶极环加成机制。

  DOI：

  10.1002/anie.201708091

文献信息

• CEPHEM COMPOUND HAVING CATECHOL GROUP
  申请人：Hisakawa Shinya

  公开号：US20130102583A1

  公开（公告）日：2013-04-25

  A compound of the formula: wherein X is —N═, —CH═, or the like; W is —CH 2 — or the like; U is —S— or the like; R 1 and R 2 are each independently hydrogen, halogen, optionally substituted lower alkyl, or the like; R 3 is hydrogen or the like; each R 4 is independently hydrogen, halogen, or the like; m is an integer from 0 to 2; Q is a single bond, or the like; G is —C(═O)—, or the like; D is a single bond, —NH—, or the like; and E is a cyclic quaternary ammonium group, or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.
• US5017569A
  申请人：——

  公开号：US5017569A

  公开（公告）日：1991-05-21
• Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model
  作者：T. G. C. Bird、J. C. Arnould、A. Bertrandie、F. H. Jung

  DOI：10.1021/jm00092a015

  日期：1992.7

  Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta-half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2, = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pK(a) values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pK(a) was sufficiently acidic.
• Regioselective<i>para</i>-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase
  作者：Stefan E. Payer、Stephen A. Marshall、Natalie Bärland、Xiang Sheng、Tamara Reiter、Andela Dordic、Georg Steinkellner、Christiane Wuensch、Susann Kaltwasser、Karl Fisher、Stephen E. J. Rigby、Peter Macheroux、Janet Vonck、Karl Gruber、Kurt Faber、Fahmi Himo、David Leys、Tea Pavkov-Keller、Silvia M. Glueck

  DOI：10.1002/anie.201708091

  日期：2017.10.23

  prFMN-dependent enzyme that is capable of directly carboxylating aromatic catechol substrates under ambient conditions. A reaction mechanism for the reversible decarboxylation involving an intermediate with a single covalent bond between a quinoid adduct and cofactor is proposed, which is distinct from the mechanism of prFMN-associated 1,3-dipolar cycloadditions in related enzymes.

  利用二氧化碳作为有机合成的碳源满足了化学品生产更加可持续性的迫切需求。在此，我们报告了酶催化儿茶酚的对位羧化，使用属于 UbiD 酶家族的 3,4-二羟基苯甲酸脱羧酶 (AroY)。晶体结构和随附的溶液数据证实，AroY 利用最近发现的异戊二烯化 FMN (prFMN) 辅因子，并且需要氧化成熟才能形成具有催化能力的 prFMNiminium 物质。本研究报告了 prFMN 依赖性酶的体外重建和激活，该酶能够在环境条件下直接羧化芳香族儿茶酚底物。提出了一种涉及醌型加合物和辅因子之间具有单共价键的中间体的可逆脱羧反应机制，该机制不同于相关酶中与 prFMN 相关的 1,3-偶极环加成机制。