6-O-甲基霉酚酸甲酯 | 60435-90-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 中文名称: 6-O-甲基霉酚酸甲酯
• 中文别名: 6-O-甲基麦考酚酸甲酯
• 英文名称: 5,7-dimethoxy-6-(5-methoxycarbonyl-3-methyl-2-pentenyl)-4-methylphthalide
• 英文别名: methyl 7-O-methyl mycophenolate；6-(4,6-dimethoxy-7-methyl-3-oxo-phthalan-5-yl)-4-methyl-hex-4-enoic acid methyl ester；6-(4,6-Dimethoxy-7-methyl-3-oxo-phthalan-5-yl)-4-methyl-hex-4-ensaeure-methylester；Methoxy-mycophenolsaeure-methylester；methyl O-methylmycophenolate；6-O-Methyl Mycophenolic Acid Methyl Ester；methyl (E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate
• CAS: 60435-90-7
• 化学式: C₁₉H₂₄O₆
• 分子量: 348.396
• InChiKey: RJVANKLHHLOSMS-IZZDOVSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-O-甲基霉酚酸甲酯 在 lithium hydroxide 、 三氯化硼 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 192.0h， 生成 霉酚酸
  参考文献：
  名称：

  麦考酚酸的全合成

  摘要：

  描述了以迈克尔加成-狄克曼环化为关键步骤，由2-香叶基-二甲基-1,3-丙酮二羧酸酯2和4-新戊酰氧基-2-丁炔醛完全收敛合成霉酚酸1的过程。

  DOI：

  10.1016/s0040-4039(98)00423-7
• 作为产物：
  描述：

  methyl (E)-3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4-dimethoxy-5-methyl-6-((pivaloyloxy)methyl)benzoate 在 jones reagent 、 potassium carbonate 、 臭氧 作用下， 以 甲醇 、 乙酸乙酯 、 丙酮 为溶剂， 反应 13.0h， 生成 6-O-甲基霉酚酸甲酯
  参考文献：
  名称：

  霉酚酸的全合成

  摘要：

  描述了天然化合物霉酚酸1的收敛的全合成。构建六取代芳族核的合成策略是基于环环化序列，其中包括迈克尔加成反应和分子内狄克曼缩合原位反应为关键步骤。取代基的随后转化提供了目标麦考酚酸1。

  DOI：

  10.1016/s0040-4020(03)00102-9

文献信息

• Convenient O-Methylation of Phenols with Dimethyl Carbonate
  作者：Youngmin Lee、Isao Shimizu

  DOI：10.1055/s-1998-1893

  日期：1998.10

  Reaction of phenols in dimethyl carbonate in the presence of cesium carbonate at 120-160 °C gave aryl methyl ethers in good yields, whereas the reaction of aliphatic alcohols gave the corresponding alkyl carbonates. This method provides a useful synthetic method for preparation of various aryl methyl ethers without using toxic methyl iodide or dimethyl sulfate. O-Methylation of the aromatic hydroxy group of estradiol was carried out in 2 steps without protection of the alcoholic hydroxy group in the same molecule.

  在碳酸铯存在下，苯酚在 120-160 °C 下与碳酸二甲酯反应，可以得到产率很高的芳基甲基醚，而脂肪醇反应则可以得到相应的碳酸烷基酯。这种方法为制备各种芳基甲基醚提供了一种有用的合成方法，而无需使用有毒的碘甲烷或硫酸二甲酯。雌二醇芳香族羟基的 O-甲基化分两步进行，无需保护同一分子中的醇羟基。
• Modular Difunctionalization of Unactivated Alkenes through Bio-Inspired Radical Ligand Transfer Catalysis
  作者：Kang-Jie Bian、David Nemoto、Shih-Chieh Kao、Yan He、Yan Li、Xi-Sheng Wang、Julian G. West

  DOI：10.1021/jacs.2c04188

  日期：2022.7.6

  iron-dependent oxygenases, we herein report the first modular, dual catalytic difunctionalization of unactivated alkenes via manganese-catalyzed radical ligand transfer (RLT). This RLT elementary step involves a coordinated nucleophile rebounding to a carbon-centered radical to form a new C–X bond in analogy to the radical rebound step in metalloenzymes. The protocol leverages the synergetic cooperation

  近年来，卤代烷在不饱和烃上的可见光介导原子转移自由基加成技术发展迅速。然而，由于其自​​由基链增长机制，除了烷基卤源上预先存在的（假）卤化物之外的多种功能不能以一步经济的方式结合到目标分子中。受细胞色素 P450 羟化酶和非血红素铁依赖性加氧酶所显示的突出反应性的启发，我们在此报告了通过锰催化自由基配体转移 (RLT) 对未活化烯烃进行的第一个模块化、双重催化双功能化。该 RLT 基本步骤涉及配位的亲核试剂反弹至碳中心自由基以形成新的 C-X 键，类似于金属酶中的自由基反弹步骤。该协议利用光催化剂和富含地球的锰复合物的协同合作，将两种自由基物质连续输送到最小功能化的烯烃，从而通过能够输送各种外部亲核试剂的高价锰物质实现自由基中间体的模块化多样化。对各种底物和氟烷基片段显示了广泛的范围（97 个示例，包括药物/天然产物基序）、温和的条件和出色的化学选择性。机理和动力学研究提供了对双重催化转化
• Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C
  作者：Xu-cheng Gan、Simona Kotesova、Alberto Castanedo、Samantha A. Green、Søren Lau Borcher Møller、Ryan A. Shenvi

  DOI：10.1021/jacs.3c05428

  日期：2023.7.26

  catalysis to merge the two cycles. Here, we report an iron-only cross-coupling via putative MHAT/SH2 steps that solves a key stereochemical problem in the synthesis of meroterpenoid eugenial C and obviates the need for nickel. The concise synthesis benefits from a conformationally locked o,o′-disubstituted benzyl bromide and a locally sourced chiral pool terpene coupling partner.

  金属氢化物氢原子转移（MHAT）已成为通过氢官能化从烯烃形成季碳的有用工具。迄今为止，烯烃与 sp 3伴侣的交叉偶联方法依赖于异双金属催化来合并两个循环。在这里，我们通过假定的 MHAT/S H 2 步骤报告了仅铁的交叉偶联，该步骤解决了类萜 eugenial C 合成中的关键立体化学问题，并且消除了对镍的需要。简洁的合成得益于构象锁定的o,o'-二取代苄基溴和本地来源的手性池萜烯偶联伴侣。
• Dual Inhibitors of Inosine Monophosphate Dehydrogenase and Histone Deacetylases for Cancer Treatment
  作者：Liqiang Chen、Daniel Wilson、Hiremagalur N. Jayaram、Krzysztof W. Pankiewicz

  DOI：10.1021/jm070864w

  日期：2007.12.27

  Mycophenolic acid (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used worldwide in transplantation. Recently, numerous studies showed its importance in cancer treatment. Consequently, MPA entered clinical trials in advanced multiple myeloma patients. Suberoylanilide hydroxamic acid (SAHA), a potent differentiation agent acting through inhibition of histone deacetylases (HDACs), was recently approved for treatment of cutaneous T cell lymphoma. We report herein the synthesis of dual inhibitors of IMPDH and HDACs. We found that mycophenolic hydroxamic acid (9, MAHA) inhibits both IMPDH (K-i = 30 nM) and HDAC (IC50 = 5.0 mu M). A modification of SAHA with groups known to interact with IMPDH afforded a SAHA analogue 14, which inhibits IMPDH (K-i = 1.7 mu M) and HDAC (IC50 = 0.06 mu M). Both MAHA (IC50 = 4.8 mu M) and SAHA analogue 14 (IC50 = 7.7 mu M) were more potent than parent compounds as antiproliferation agents. They were also significantly more potent as differentiation inducers.
• Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid
  作者：Peter H. Nelson、Elsie Eugui、Ching C. Wang、Anthony C. Allison

  DOI：10.1021/jm00164a057

  日期：1990.2

  The syntheses and immunosuppressive bioassays of 12 side-chain variants of mycophenolic acid are described. The compounds were made either from mycophenolic acid itself or from 5-(chloromethyl)-1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisoben zofuran, a versatile intermediate for the synthesis of diverse side-chain variants. Replacement of the methylated E double bond of the natural product with a triple bond, a Z double bond, a saturated bond, or a sulfur atom, with overall chain lengths equal to or greater than that of mycophenolic acid, produced compounds devoid of significant activity. Replacement of the side-chain double bond with difluoro, dibromo, or unsubstituted cyclopropane rings also removed most activity. Replacement of the double bond with an allenic linkage yielded a compound with about one-fifth of the immunosuppressive activity of mycophenolic acid. Some possible causes for the unusual specificity of structure and activity are discussed.