4-(1,3-dihydroxypropyl)benzoic acid methyl ester | 862187-65-3

• 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: 4-(1,3-dihydroxypropyl)benzoic acid methyl ester
• 英文别名: 1-(4-methoxycarbonylphenyl)-1,3-propanediol；Methyl 4-(1,3-dihydroxypropyl)benzoate
• CAS: 862187-65-3
• 化学式: C₁₁H₁₄O₄
• 分子量: 210.23
• InChiKey: MSTNSVUBJIOYNN-UHFFFAOYSA-N

物化性质

• 沸点：
  381.6±27.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1,3-dihydroxypropyl)benzoic acid methyl ester 在 叔丁基氯化镁 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 生成 5'-O-trans-[4-(4-methoxycarbonylphenyl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating > 19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and > 12-fold higher araCTP levels in the liver than in the bone marrow, representing a > 120-fold and > 28-fold improvement, respectively, over araC administration.

  DOI：

  10.1021/jm0607449
• 作为产物：
  描述：

  4-(3-甲氧基-3-氧代丙酰基)苯甲酸甲酯 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以95%的产率得到4-(1,3-dihydroxypropyl)benzoic acid methyl ester
  参考文献：
  名称：

  在室温下使用硼氢化钠/ MeOH还原芳香族和脂肪族酮酯

  摘要：

  还原酮酯是生产二醇的有价值的替代方法。在室温和短的反应时间下，硼氢化钠/ MeOH系统有效地还原了以α-酮酸酯为最具反应性的α，β，γ和δ-酮酸酯。由于存在以某种方式促进环中间体形成的氧代基团，有效地降低了酯的官能度。如预期的那样，化学选择性实验表明，使用该系统不会降低酯的官能度。这项研究提出了各种酮酯向其相应的二醇的简单，简便且良性的还原过程。

  DOI：

  10.1016/j.tet.2010.04.062

文献信息

• Novel 2'-C-methyl nucleoside derivatives
  申请人：Reddy Raja K.

  公开号：US20050182252A1

  公开（公告）日：2005-08-18

  Compounds of Formula I, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described:

  化合物I的配方、立体异构体以及其药用可接受的盐或前药，它们的制备以及它们用于治疗丙型肝炎病毒感染的用途被描述：
• [EN] NOVEL CYCLIC PHOSPHATE DIESTERS OF 1,3-PROPANE-1-ARYL DIOLS AND THEIR USE IN PREPARING PRODRUGS<br/>[FR] NOUVEAUX DIESTERS PHOSPHORIQUES CYCLIQUES DE DIOLS DE 1,3-PROPANE-1-ARYLIQUES ET LEUR UTILISATION POUR LA PREPARATION DE PROMEDICAMENTS
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2004041834A2

  公开（公告）日：2004-05-21

  Compounds of Formula (I), their preparation and synthetic intermediates, and their use in the synthesis of prodrugs; wherein: V and L are trans relative to one another; V is selected from group consisting of carbocyclic aryl, substituted carbocyclic aryl, heteroaryl, and substituted heteroaryl; and L is a leaving group selected from the group consisting of halogen, alkyl sulfonate, aryloxy optionally substituted with 1-2 substituents, N-containing heteroaryl, and N-hydroxy-nitrogen containing heteroaryl; and salts thereof.

  公式（I）的化合物，其制备和合成中间体，以及它们在前药合成中的应用；其中：V和L相对于彼此是反式的；V选自群体，包括环烷基芳基，取代环烷基芳基，杂环芳基和取代杂环芳基；L是离去基，选自群体，包括卤素，烷基磺酸盐，取代1-2个取代基的芳氧基，含N的杂环芳基和含N-羟基-氮的杂环芳基；以及其盐。
• Novel cyclic phosphate diesters of 1,3-propane-1-aryl diols and their use in preparing prodrugs
  申请人：——

  公开号：US20040192651A1

  公开（公告）日：2004-09-30

  Compounds of Formula I, their preparation and synthetic intermediates, and their use in the synthesis of prodrugs: 1 wherein: V and L are trans relative to one another; V is selected from group consisting of carbocyclic aryl, substituted carbocyclic aryl, heteroaryl, and substituted heteroaryl; and L is a leaving group selected from the group consisting of halogen, alkyl sulfonate, aryloxy optionally substituted with 1-2 substituents, N-containing heteroaryl, and N-hydroxy-nitrogen containing heteroaryl; and salts thereof.

  公式I的化合物，它们的制备和合成中间体，以及它们在前药合成中的应用： 其中： V和L是相对于彼此的反式； V选自群组，包括碳环芳基，取代的碳环芳基，杂环芳基和取代的杂环芳基； L是离去基，选自群组，包括卤素，烷基磺酸盐，取代1-2个取代基的芳氧基，含氮杂环和含N-羟基-氮杂环； 以及它们的盐。
• Electrochemical ring-opening 1,3-dihydroxylation of arylcyclopropanes with H₂O
  作者：Jianhua Cai、Yuxi Wen、Wei Sheng、Xuejin Huang、Ye Zheng、Chunlan Song、Jiakun Li

  DOI：10.1039/d3gc02283h

  日期：——

  dihydroxylation of alkenes is one of the most powerful synthetic tools for delivering two hydroxyl groups at vicinal positions. The direct formation of 1,3-diols remains a formidable challenge, yet dihydroxyl groups are broadly present in bioactive compounds, and are currently only available synthetically via multiple steps. The oxidative ring-opening of arylcyclopropanes has been demonstrated to access various

  传统的烯烃二羟基化是在邻位提供两个羟基的最强大的合成工具之一。直接形成 1,3-二醇仍然是一个艰巨的挑战，但二羟基广泛存在于生物活性化合物中，目前只能通过多个步骤合成。芳基环丙烷的氧化开环已被证明可以得到各种 1,3-双官能化化学物质，但由于 1,3-二醇本身很容易被进一步氧化，所以尚未直接合成 1,3-二醇。在此，我们报告了一种简便有效的 1,3-二醇策略，涉及用 H 2控制芳基环丙烷的电化学 C-C 键断裂O作为最终的绿色羟基源。此外，该方案以其高原子经济性、广泛的底物范围和优异的官能团耐受性而脱颖而出，因此适合复杂天然产物和药物衍生物的合成。
• NOVEL CYCLIC PHOSPHATE DIESTERS OF 1,3-PROPANE-1-ARYL DIOLS AND THEIR USE IN PREPARING PRODRUGS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP1556393B1

  公开（公告）日：2013-12-25