3,5-取代-1,2,4-恶二唑是一类重要的杂环化合物,作为脂键、酰胺键等常见化学键的生物电子等排体在药物化学领域有着重要应用价值,因此其合成方法也受到广泛关注。本文归纳总结了3,5-取代-1,2,4-恶二唑类化合物的合成研究进展,主要介绍了以氰基、酮醛、酰胺肟、酮肟、炔烃等为起始原料合成3,5-取代-1,2,4-恶二唑类化合物的研究进展及其反应机理。最后对该类化合物的合成研究进展进行了总结和展望。
3,5-Substituted-1,2,4-oxadiazole is an important class of heterocyclic compounds. As the bio-isostere of common chemical bonds such as lipid bonds and amide bonds, it has important ap-plication value in the field of medicinal chemistry. Synthetic methods have also received wide-spread attention. This article summarizes the progress in the synthesis of 3,5-substituted-1,2,4-oxadiazole compounds, and mainly introduces the synthesis of starting mate-rials with cyano groups, ketone aldehydes, amide oximes, ketoximes, alkynes, etc. research pro-gress and reaction mechanism of 3,5-substituted-1,2,4-oxadiazole compounds. Finally, the research progress of the synthesis of these compounds is summarized and prospected.
Research Progress of 3,5-Substituted-1,2,4-Oxadiazole Compounds
Xiangdong Meng, Rajendran Satheeshkumar, Wenlong Wang
School of Pharmacy, Jiangnan University, Wuxi Jiangsu
Received: Mar. 16th, 2021; accepted: May 21st, 2021; published: May 28th, 2021
ABSTRACT
3,5-Substituted-1,2,4-oxadiazole is an important class of heterocyclic compounds. As the bio-isostere of common chemical bonds such as lipid bonds and amide bonds, it has important application value in the field of medicinal chemistry. Synthetic methods have also received widespread attention. This article summarizes the progress in the synthesis of 3,5-substituted-1,2,4-oxadiazole compounds, and mainly introduces the synthesis of starting materials with cyano groups, ketone aldehydes, amide oximes, ketoximes, alkynes, etc. research progress and reaction mechanism of 3,5-substituted-1,2,4-oxadiazole compounds. Finally, the research progress of the synthesis of these compounds is summarized and prospected.
参考文献ReferencesTiemann, F. and Krüger, P. (1884) Ueber Amidoxime und Azoxime. European Journal of Inorganic Chemistry, 17, 1685-1698. <br>https://doi.org/10.1002/cber.18840170230Diana, G.D., Volkots, D.L., Nitz, T.J., et al. (1994) Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity. Journal of Medicinal Chemistry, 37, 2421-2436.
<br>https://doi.org/10.1021/jm00041a022Borg, S., Vollinga, R.C., Labarre, M., et al. (1999) Design, Synthesis, and Evaluation of Phe-Gly Mimetics: Heterocyclic Building Blocks for Pseudopeptides. Journal of Medicinal Chemistry, 42, 4331-4342.
<br>https://doi.org/10.1021/jm990197+Orlek, B.S., Blaney, F.E., Brown, F., et al. (1991) Comparison of Azabi-cyclic Esters and Oxadiazoles as Ligands for the Muscarinic Receptor. Journal of Medicinal Chemistry, 34, 2726-2735. <br>https://doi.org/10.1021/jm00113a009Watjen, F., Baker, R., Engelstoff, M., et al.(1989) Novel Benzodiazepine Receptor Partial Agonists: Oxadiazolylimidazobenzodiazepines. Journal of Medicinal Chemistry, 32, 2282-2291. <br>https://doi.org/10.1021/jm00130a010Carroll, F.I., Gray, J.L., Abraham, P., et al. (1993) 3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane Analogs of Cocaine: Affinities at the Cocaine Binding Site at the Dopamine, Serotonin, and Norepinephrine Transporters. Journal of Medicinal Chemistry, 36, 2886-2890. <br>https://doi.org/10.1021/jm00072a007Ankersen, M., Peschke, B., Hansen, B.S. and Hansen, T.K. (1997) In-vestigation of Bioisosters of the Growth Hormone Secretagogue l-692,429. Bioorganic & Medicinal Chemistry Letters, 7, 1293-1298.
<br>https://doi.org/10.1016/S0960-894X(97)00216-3Chen, C., Senanayake, C.H., Bill, T.J., Larsen, R.D., et al. (1994) Improved Fischer Indole Reaction for the Preparation of N,N-Dimethyltryptamines: Synthesis of L-695,894, a Potent 5-HT1D Receptor Agonist. The Journal of Organic Chemistry, 59, 3738-3741. <br>https://doi.org/10.1021/jo00092a046Robert, J.M., Anna, M.B., Mari, R.C., et al. (1999) Potent, Selective Human β3 Adrenergic Receptor Agonists Containing a Substituted Indoline-5-Sulfonamide Pharmacophore. Bioorganic & Medicinal Chemistry Letters, 9, 1869-1874.
<br>https://doi.org/10.1016/S0960-894X(99)00277-2Li, Z., Chen, W., Hale, J.J., Lynch, C.L., et al. (2005) Dis-covery of Potent 3,5-Diphenyl-1,2,4-Oxadiazole Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists with Exceptional Selectivity against S1P2 and S1P3. Journal of Medicinal Chemistry, 48, 6169-6173. <br>https://doi.org/10.1021/jm0503244Roppe, J., Smith, N.D., Huang, D., et al. (2004) Discovery of Novel Het-eroarylazoles That Are Metabotropic Glutamate Subtype 5 Receptor Antagonists with Anxiolytic Activity. Journal of Medicinal Chemistry, 47, 4645-4648.
<br>https://doi.org/10.1021/jm049828cFrizon, T.E., Rampon, D.S., Gallardo, H., et al. (2012) Selenides and Diselenides Containing Oxadiazoles: A New Class of Functionalised Materials. Liquid Crystals, 39, 769-777. <br>https://doi.org/10.1080/02678292.2012.680505Pace, A., Pibiri, I., Piccionello, A.P., et al. (2006) Synthesis and Characterization of a Series of Alkyloxadiazolylpyridinium Salts as Perspective Ionic Liquids. Heterocycles, 68, 2653-2661. <br>https://doi.org/10.3987/COM-06-10895Pibiri, I., Piccionello, A.P., Calabrese, A., et al. (2010) Fluorescent Hg2+ Sensors: Synthesis and Evaluation of a Tren-Based Starburst Molecule Containing Fluorinated 1,2,4-Oxadiazoles. European Journal of Organic Chemistry, 2010, 4549-4553. <br>https://doi.org/10.1002/ejoc.201000763Li, Q., Cui, L., Zhong, C., et al. (2014) Synthesis of New Bipolar Host Materials Based on 1,2,4-Oxadiazole for Blue Phosphorescent OLEDs. Dyes and Pigments, 101, 142-149. <br>https://doi.org/10.1016/j.dyepig.2013.09.029Fu, Z., He, C. and Chen, F. (2012) Synthesis and Characteristics of a Novel, High-Nitrogen, Heat-Resistant, Insensitive Material (NOG2Tz). Journal of Materials Chemistry, 22, 60-63. <br>https://doi.org/10.1039/C1JM14232AKo, D., Patel, H.A. and Yavuz, C.T. (2015) Synthesis of Nanoporous 1,2,4-Oxadiazole Networks with High CO2 Capture Capacity. Chemical Communications, 51, 2915-2917. <br>https://doi.org/10.1039/C4CC08649JPorcheddu, A., Cadoni, R. and De Luca, L. (2011) A Fast and Efficient One-Pot Microwave Assisted Synthesis of Variously Disubstituted 1,2,4-Oxadiazoles. Organic & Biomolecular Chem-istry, 9, 7539-7546.
<br>https://doi.org/10.1039/c1ob06055dRamu, T., Prasanthi, S., Mangarao, N., et al. (2013) A Simple and Straightforward Protocol to 3,5-Disubstituted 1,2,4-Oxadiazoles from Carboxylic Acids. Chemistry Letters, 42, 722-724. <br>https://doi.org/10.1246/cl.130187Laetitia, D., Jean, C.L., Daniel, C., et al. (2010) Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles Using Ionic Liquid-Phase Organic Synthesis (IoLiPOS) Methodology. Tetrahedron, 66, 986-994.
<br>https://doi.org/10.1016/j.tet.2009.11.079Nowrouzi, N., Khalili, D. and Irajzadeh, M. (2015) One-Pot Synthe-sis of 1,2,4-Oxadiazoles from Carboxylic Acids Using 4-(dimethylamino)pyridinium Acetate as Efficient, Regenerable, and Green Catalyst with Ionic Liquid Character. Journal of the Iranian Chemical Society, 12, 801-806. <br>https://doi.org/10.1007/s13738-014-0542-3Babak, K. and Fariba, S. (2007) Magnesia-Supported Hydroxyl-amine Hydrochloride in the Presence of Sodium Carbonate as an Efficient Reagent for the Synthesis of 1,2,4-Oxadiazoles from Nitriles. Tetrahedron Letters, 48, 2829-2832.
<br>https://doi.org/10.1016/j.tetlet.2007.02.105Rostamizadeh, S., Ghaieni, H.R., Aryan, R. and Amani, A.M. (2010) Clean One-Pot Synthesis of 1,2,4-Oxadiazoles under Solvent-Free Conditions Using Microwave Irradiation and Potassium Fluoride as Catalyst and Solid Support. Tetrahedron, 66, 494-497. <br>https://doi.org/10.1016/j.tet.2009.11.063Kaboudin, B. and Malekzadeh, L. (2011) Organic Reactions in Water: An Efficient Method for the Synthesis of 1,2,4-Oxadiazoles in Water. Tetrahedron Letters, 52, 6424-6426. <br>https://doi.org/10.1016/j.tetlet.2011.09.081Baykov, S., Sharonova, T., Shetnev, A., Rozhkov, S., et al. (2017) The First One-Pot Ambient-Temperature Synthesis of 1,2,4-Oxadiazoles from Amidoximes and Carboxylic Acid Esters. Tetrahedron, 73, 945-951.
<br>https://doi.org/10.1016/j.tet.2017.01.007Suresh, D., Kanagaraj, K. and Pitchumani, K. (2014) Microwave Promoted One-Pot Synthesis of 2-Aryl Substituted 1,3,4-Oxadiazoles and 1,2,4-Oxadiazole Derivatives Using Al3+-K10 Clay as a Heterogeneous Catalyst. Tetrahedron Letters, 55, 3678-3682. <br>https://doi.org/10.1016/j.tetlet.2014.05.004Yoshimura, A., Nguyen, K.C., Klasen, S.C., et al. (2015) Prepara-tion, Structure, and Versatile Reactivity of Pseudocyclic Benziodoxole Triflate, New Hypervalent Iodine Reagent. Chem-ical Communications, 51, 7835-7838.
<br>https://doi.org/10.1039/C5CC02009CYoshimura, A., Nguyen, K.C., Klasen, S.C., Postnikov, P.S., et al. (2016) Hypervalent Iodine-Catalyzed Synthesis of 1,2,4-Oxadiazoles from Aldoximes and Nitriles. Asian Journal of Organic Chemistry, 5, 1128-1133.
<br>https://doi.org/10.1002/ajoc.201600247Nikodemiak, P. and Koert, U. (2017) Metal-Catalyzed Synthesis of Functionalized 1,2,4-Oxadiazoles from Silyl Nitronates and Nitriles. Advanced Synthesis & Catalysis, 359, 1708-1716. <br>https://doi.org/10.1002/adsc.201601378Vale, J.A., Faustino, W.M., Zampieri, D.S., et al. (2012) Lanthanide Nitrates as Lewis Acids in the One-Pot Synthesis of 1,2,4-Oxadiazole Derivatives. Journal of the Brazilian Chemical Society, 23, 1437-1440.
<br>https://doi.org/10.1590/S0103-50532012005000002Tka, N. and Hassine, B.B. (2010) One-Pot Synthesis of New, Biologically Active 3,5-Disubstituted-1,2,4-Oxadiazoles. Synthetic Communications, 40, 3168-3176. <br>https://doi.org/10.1080/00397910903370717Wang, W., Xu, H., Xu, Y., et al. (2016) Base-Mediated One-Pot Synthesis of 1,2,4-Oxadiazoles from Nitriles, Aldehydes and Hydroxylamine Hydrochloride without Addition of Extra Oxidant. Organic and Biomolecular Chemistry, 14, 9814-9822. <br>https://doi.org/10.1039/C6OB01794KZhang, F.-L., Wang, Y.-F. and Chiba, S. (2013) Orthogonal Aerobic Conversion of N-Benzyl Amidoximes to 1,2,4-Oxadiazoles or Quinazolinones. Organic & Biomolecular Chemistry, 11, 6003-6006.
<br>https://doi.org/10.1039/c3ob41393dParker, P.D. and Pierce, J.G. (2016) Synthesis of 1,2,4-Oxadiazoles via DDQ-Mediated Oxidative Cyclization of Amidoximes. Synthesis, 48, 1902-1909. <br>https://doi.org/10.1055/s-0035-1561597Lade, J.J., Patil, B.N., Vadagaonkar, K.S. and Chaskar, A.C. (2017) Oxidative Cyclization of Amidoximes and Thiohydroximic Acids: A Facile and Efficient Strategy for Accessing 3,5-Disubstituted 1,2,4-Oxadiazoles and 1,4,2-Oxathiazoles. Tetrahedron Letters, 58, 2103-2108. <br>https://doi.org/10.1016/j.tetlet.2017.04.045Kivrak, A. and Zora, M. (2014) A Novel Synthesis of 1,2,4-Oxadiazoles and Isoxazoles. Tetrahedron, 70, 817-831.
<br>https://doi.org/10.1016/j.tet.2013.12.043Bian, Q., Wu, C., Yuan, J., et al. (2020) Iron Nitrate-Mediated Selec-tive Synthesis of 3-Acyl-1,2,4-Oxadiazoles from Alkynes and Nitriles: The Dual Roles of Iron Nitrate. The Journal of Organic Chemistry, 85, 4058-4066.
<br>https://doi.org/10.1021/acs.joc.9b03070