2-(4-((tert-butyldimethylsilyl)oxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehyde | 138768-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 2-(4-((tert-butyldimethylsilyl)oxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehyde
• 英文别名: 2-(4-tert-butyldimethylsilyloxy-1,3-dihydro-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)acetaldehyde；2-(4-Tert-butyldimethylsilyloxy-1,3-dihydro-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) acetaldehyde；2-[4-[tert-butyl(dimethyl)silyl]oxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl]acetaldehyde
• CAS: 138768-41-9
• 化学式: C₁₈H₂₆O₅Si
• 分子量: 350.487
• InChiKey: IMKYNIUGLIEQKC-UHFFFAOYSA-N

物化性质

• 沸点：
  477.5±45.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-((tert-butyldimethylsilyl)oxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehyde 在 lithium hydroxide 、 四丁基氟化铵 、 丙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 4.75h， 生成 霉酚酸
  参考文献：
  名称：

  The orthoester Claisen rearrangement in the synthesis of mycophenolic acid

  摘要：

  原酸酯克莱森重排被用作将乙醛部分立体定向地轻松转化为麦考酚酸的 (E)-4-甲基己-4-烯酸侧链的关键反应。

  DOI：

  10.1039/c39910001579
• 作为产物：
  描述：

  霉酚酸 在 咪唑 、 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 13.5h， 生成 2-(4-((tert-butyldimethylsilyl)oxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehyde
  参考文献：
  名称：

  Mycophenolic anilides as broad specificity inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors

  摘要：

  Inosine-5'-monophosphate dehydrogenase (IMPDH) is a potential target for microorganisms. However, identifying inhibitor design determinants for IMPDH orthologs continues to evolve. Herein, a series of mycophenolic anilide inhibitors of Cryptosporidium parvum and human IMPDHs are reported. Furthermore, molecular docking of 12 (e.g. SH-19; CpIMPDH Ki,app = 0.042 ± 0.015 µM, HsIMPDH2 Ki,app = 0.13 ± 0.05 µM) supports different binding modes with the two enzymes. For CpIMPDH the inhibitor extends into a pocket in an adjacent subunit. In contrast, docking suggests the inhibitor interacts with Ser276 in the NAD binding site in HsIMPDH2, as well as an adjacent pocket within the same subunit. These results provide further guidance for generating IMPDH inhibitors for enzymes found in an array of pathogenic microorganisms, including Mycobacterium tuberculosis.

  DOI：

  10.1016/j.bmcl.2020.127543

文献信息

• 5-substituted derivatives of mycophenolic acid
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05493030A1

  公开（公告）日：1996-02-20

  The disclosed hexenoic acid side-chain derivatives of mycophenolic acid are therapeutic agents advantageous in the treatment of disease states indicated for mycophenolic acid and/or mycophenolate mofetil, including immune, inflammatory, tumor, proliferative, viral or psoriatic disorders.

  揭示的己烯酸侧链衍生物是治疗代理，有利于治疗与己烯酸和/或麦考酚酯有关的疾病状态，包括免疫、炎症、肿瘤、增殖、病毒或银屑病等疾病。
• Total synthesis of mycophenolic acid
  作者：Ricardo A. de la Cruz、Francisco X. Talamás、Alfredo Vázquez、Joseph M. Muchowski

  DOI：10.1139/v97-078

  日期：1997.6.1

  A total synthesis of mycophenolic acid is reported. Diels–Alder reaction of [5-methoxy-3-(1-methoxypropenyl)-4,5-dihydrofuran-2-yloxy]-trimethylsilane with 3-benzenesulfinyl-5H-furan-2-one afforded...

  报道了霉酚酸的全合成。[5-甲氧基-3-(1-甲氧基丙烯基)-4,5-二氢呋喃-2-基氧基]-三甲基硅烷与3-苯亚磺酰基-5H-呋喃-2-酮的Diels-Alder反应得到...
• The synthesis of mycophenolic acid
  作者：John W. Patterson

  DOI：10.1016/s0040-4020(01)80398-7

  日期：1993.5

  A new synthesis of mycophenolic acid 1, has been accomplished using silyloxy-1,3-cyclohexadiene 9 which undergoes cycloaddition to dimethyl acetylenedicarboxylate and subsequent elimination of ethylene (Alder-Rickert reaction) to give the trisubstituted dimethyl phthalate 11. After conversion of 11 to phthalide 16, the (E)-4-methyl-4-hexenoic acid side-chain was constructed via an orthoester Claisen

  使用甲硅烷氧基-1,3-环己二烯9完成了霉酚酸1的新合成，该甲硅烷氧基-1,3-环己二烯9经过环加成反应生成二甲基乙炔二羧酸酯，然后消除乙烯（Alder-Rickert反应），得到邻苯二甲酸三取代二甲酯11。在将11转化为邻苯二甲酸酯16后，使用烯丙醇19和原乙酸三乙酯通过原酸酯克莱森重排构建（E）-4-甲基-4-己酸侧链。
• Asymmetric Synthesis and Stereochemical Assignment of RS-97613, a Potent Immunosuppressive and Antiinflammatory Agent
  作者：David B. Smith、Ann Marie Waltos、David G. Loughhead、Robert J. Weikert、David J. Morgans、John C. Rohloff、John O. Link、Rong-rong Zhu

  DOI：10.1021/jo951883t

  日期：1996.1.1
• Mycophenolic anilides as broad specificity inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors
  作者：Seungheon Lee、Angela F. Ku、Mohana Rao Vippila、Yong Wang、Minjia Zhang、Xingyou Wang、Lizbeth Hedstrom、Gregory D. Cuny

  DOI：10.1016/j.bmcl.2020.127543

  日期：2020.12

  Inosine-5'-monophosphate dehydrogenase (IMPDH) is a potential target for microorganisms. However, identifying inhibitor design determinants for IMPDH orthologs continues to evolve. Herein, a series of mycophenolic anilide inhibitors of Cryptosporidium parvum and human IMPDHs are reported. Furthermore, molecular docking of 12 (e.g. SH-19; CpIMPDH Ki,app = 0.042 ± 0.015 µM, HsIMPDH2 Ki,app = 0.13 ± 0.05 µM) supports different binding modes with the two enzymes. For CpIMPDH the inhibitor extends into a pocket in an adjacent subunit. In contrast, docking suggests the inhibitor interacts with Ser276 in the NAD binding site in HsIMPDH2, as well as an adjacent pocket within the same subunit. These results provide further guidance for generating IMPDH inhibitors for enzymes found in an array of pathogenic microorganisms, including Mycobacterium tuberculosis.