Multicomponent Reactions

Green Techniques for Organic Synthesis and Medicinal Chemistry

Volumn , Issue , 2012, Pages 497-522

  Huang, Yijun ^a   Yazbak, Ahmed ^a   Dömling, Alexander ^a  

^a UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Green chemistry, and sustainability; MCR "on water," as an "on water" reaction; MCR acceleration in water; MCR chemistry, as the prototypical green chemistry; MCR, closely approaching concept of "ideal synthesis"; MCR, materials reacting, incorporating atoms of the educts; MCRs, and advantages in drug discovery; MCRs, new approach to efficient synthesis of diverse compound libraries; SFC in pharmaceutical industry, and solvent saving; Solvent free organic, for clean, safe, easy to perform procedures

Indexed keywords

EID: 84867871621     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470711828.ch18     Document Type: Chapter

References (117)

1. Anastas, P. and Eghbali, N. (2010) Green chemistry: principles and practice. Chem. Soc. Rev., 39, 301-312.
2. Rosamilia, A.E., Strauss, C.R., and Scott, J.L. (2007) Distillable ionic liquids for a new multicomponent reaction. Pure Appl. Chem., 79, 1869-1877.
3. Sheldon, R.A. (1992) Organic synthesis -past, present and future. Chem. Ind., 903-906.
4. Constable, D.J.C., Dunn, P.J., Hayler, J.D. et al. (2007) Key green chemistry research areas -a perspective from pharmaceutical manufacturers. Green Chem., 9, 411-420.
5. D€omling, A. (2005) Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem. Rev., 106, 17-89.
6. Da Silva, E.N. (2007) Multicomponent reactions as a green approach. Res. J. Chem. Environ., 11, 90-91.
7. D€omling, A. and Ugi, I. (1993) The 7-component reaction. Angew. Chem. Int. Ed., 32, 563-564.
8. Hulme, C. and Gore, V. (2003) "Multi-component reactions: Emerging chemistry in drug discovery" 'from xylocain to crixivan'. Curr. Med. Chem., 10, 51-80.
9. Weber, L. (2002) The application of multi-component reactions in drug discovery. Curr. Med. Chem., 9, 2085-2093.
10. Wei, W., Keh, C.C.K., Li, C.-J., and Varma, R.S. (2004) Water as a reaction medium for clean chemical processes. Clean Technol. Environ. Policy, 6, 250-257.
11. Hailes, H.C. (2006) Reaction solvent selection: the potential of water as a solvent for organic transformations. Org. Process Res. Dev., 11, 114-120.
12. Liu, L. and Wang, D. (2010) On water" for green chemistry, in Handbook of Green Chemistry (ed P.T. Anastas), John Wiley & Sons, Ltd, Weinheim.
13. Chanda, A. and Fokin, V.V. (2009) Organic synthesis "On water". Chem. Rev., 109, 725-748.
14. Lindstrom, U.M. (2007) Organic Reactions in Water: Principles, Strategies and Applications, Blackwell, Oxford.
15. Engberts, J.B.F.N. (2007) Organic chemistry in water: green and fast, in Methods and Reagents for Green Chemistry (eds P. Tundo, A. Perosa, and F. Zecchini), John Wiley & Sons, Ltd, Hoboken.
16. Engberts, J.B.F.N. and Blandamer, M.J. (2001) Understanding organic reactions in water: from hydrophobic encounters to surfactant aggregates. Chem. Commun., 1701-1708.
17. Pirrung, M.C. (2006) Acceleration of organic reactions through aqueous solvent effects. Chem. Eur. J., 12, 1312-1317.
18. Kumaravel, K. and Vasuki, G. (2009) Multicomponent reactions in water. Curr. Org. Chem., 13, 1820-1841.
19. Pirrung, M.C. and Das Sarma, K. (2004) Multicomponent reactions are accelerated in water. J. Am. Chem. Soc., 126, 444-445.
20. Pirrung, M.C. and Das Sarma, K. (2005) Aqueous medium effects on multi-component reactions. Tetrahedron, 61, 11456-11472.
21. Pirrung, M.C., Sarma, K.D., and Wang, J.M. (2008) Hydrophobicity and mixing effects on select heterogeneous, water-accelerated synthetic reactions. J. Org. Chem., 73, 8723-8730.
22. Pirrung, M.C. and Wang, J.M. (2009) Multicomponent reactions of cyclobutanones. J. Org. Chem., 74, 2958-2963.
23. Mironov, M.A., Ivantsova, M.N., Tokareva, M.I., and Mokrushin, V.S. (2005) Acceleration of the Passerini reaction in the presence of nucleophilic additives. Tetrahedron Lett., 46, 3957-3960.
24. Candeias, N.R., Cal, P., Andre, V. et al. (2010)Water as the reaction medium for multicomponent reactions based on boronic acids. Tetrahedron, 66, 2736-2745.
25. Tomasi, J., Mennucci, B., and Cammi, R. (2005) Quantum mechanical continuum solvation models. Chem. Rev., 105, 2999-3094.
26. Narayan, S., Muldoon, J., Finn, M.G. et al. (2005) "On water": unique reactivity of organic compounds in aqueous suspension. Angew. Chem. Int. Ed., 44, 3275-3279.
27. Klijn, J.E. and Engberts, J. (2005) Organic chemistry -fast reactions 'on water'. Nature, 435, 746-747.
28. Shapiro, N. and Vigalok, A. (2008) Highly efficient organic reactions "on water", "in water", and both. Angew. Chem. Int. Ed., 47, 2849-2852.
29. Lin, Q., O'neill, J.C., and Blackwell, H.E. (2005) Small molecule macroarray construction via Ugi four-component reactions. Org. Lett., 7, 4455-4458.
30. Cruz-Acosta, F., De Armas, P., and Garcia-Tellado, F. (2010) A metal-free, three-component manifold for the C2-functionalization of 1-substituted imidazoles operating "on water". Synlett, 2421-2424.
31. Trofimov, B.A., Andriyankova, L.V., Belyaeva, K.V. et al. (2010) C2-functionalization of 1-substituted imidazoles with aldehydes and electron-deficient acetylenes: a novel three-component reaction. Eur. J. Org. Chem., 1772-1777.
32. Cruz-Acosta, F., Santos-Exposito, A., De Armas, P., and Garcia-Tellado, F. (2009) Lewis base-catalyzed three-component strecker reaction on water. An efficient manifold for the direct a-cyanoamination of ketones and aldehydes. Chem. Commun., 6839-6841.
33. McKay, C.S., Kennedy, D.C., and Pezacki, J.P. (2009) Studies of multicomponent Kinugasa reactions in aqueous media. Tetrahedron Lett., 50, 1893-1896.
34. Pal, R., Ghosh, S.C., Chandra, K., and Basak, A. (2007) Synthesis of beta-lactams using the Kinugasa reaction. Synlett, 2321-2330.
35. Halimehjani, A.Z., Marjani, K., and Ashouri, A. (2010) Synthesis of dithiocarbamate by Markovnikov addition reaction in aqueous medium. Green Chem., 12, 1306-1310.
36. Chen, H. and Shi, D. (2010) Efficient one-pot synthesis of novel spirooxindole derivatives via three-component reaction in aqueous medium. J. Comb. Chem., 12, 571-576.
37. Loupy, A. (1999) Solvent-free reactions, in Modern Solvents in Organic Synthesis, Topics in Current Chemistry Series 206 (ed. P. Knochel), Springer-Verlag, Berlin.
38. Cave, G.W.V., Raston, C.L., and Scott, J.L. (2001) Recent advances in solventless organic reactions: towards benign synthesis with remarkable versatility. Chem. Commun., 2159-2169.
39. Shearouse, W.C., Waddell, D.C., and Mack, J. (2009) Alternative solvent-free methodologies in the synthesis of pharmaceutical drugs. Curr. Opin. Drug Discov. Devel., 12, 772-783.
40. Kumar, R., Raghuvanshi, K., Verma, R.K., and Singh, M.S. (2012) Application of cyclic-1,3-diketones in domino and multicomponent reactions: facile route to highly functionalized chromeno[2,3-d]pyrimidinones and diazabenzo[ b]fluorenones under solvent-free conditions. Tetrahedron Lett., 51, 5933-5936.
41. Elinson, M.N., Ilovaisky, A.I., Merkulova, V.M. et al. (2010) Solvent-free cascade reaction: direct multicomponent assembling of 2-amino-4H-chromene scaffold from salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes. Tetrahedron, 66, 4043-4048.
42. Naimi-Jamal, M.R., Mashkouri, S., and Sharifi, A. (2010) An efficient, multicomponent approach for solvent-free synthesis of 2-amino-4H-chromene scaffold. Mol. Divers., 14, 473-477.
43. Dabiri, M., Delbari, A.S., and Bazgir, A. (2007) A novel three-component, one-pot synthesis of 1,2-dihydro-1-arylnaphtho [1,2-e][1,3]oxazine-3-one derivatives under microwave-assisted and thermal solvent-free conditions. Synlett, 821-823.
44. Wang, G.W. and Miao, C.B. (2006) Environmentally benign one-pot multi-component approaches to the synthesis of novel unsymmetrical 4-arylacridinediones. Green Chem., 8, 1080-1085.
45. Liu, N.J., Cao, S., Wu, J.J. et al. (2008) Solvent-free Ugi four-component condensation: application to synthesis of philanthotoxins-12 analogues. Tetrahedron, 64, 3966-3974.
46. Jida, M., Malaquin, S., Deprez-Poulain, R. et al. (2010) Synthesis of five-and six-membered lactams via solventfree microwave Ugi reaction. Tetrahedron Lett., 51, 5109-5111.
47. Srihari, P., Singh, V.K., Bhunia, D.C., and Yadav, J.S. (2009) One-pot three-component coupling reaction: solvent-free synthesis of novel 3-substituted indoles catalyzed by PMA-SiO2. Tetrahedron Lett., 50, 3763-3766.
48. Koszelewski, D., Szymanski, W., Krysiak, J., and Ostaszewski, R. (2008) Solvent-free Passerini reactions. Syn. Commun., 38, 1120-1127.
49. Nun, P., Martinez, J., and Lamaty, F. (2010) Microwave-assisted neat procedure for the Petasis reaction. Synthesis, 2063-2068.
50. Kalinski, C., Umkehrer, M., Weber, L. et al. (2010) On the industrial applications of MCRs: molecular diversity in drug discovery and generic drug synthesis. Mol. Divers., 14, 513-522;
51. Malaquin, S., Jida, M., Gesquiere, J.C. et al. (2010) Ugi reaction for the synthesis of 4-aminopiperidine-4-carboxylic acid derivatives. Application to the synthesis of carfentanil and remifentanil. Tetrahedron Lett., 51, 2983-2985;
52. Kalinski, C., Lemoine, H., Schmidt, J. et al. (2008) Multicomponent reactions as a powerful tool for generic drug synthesis. Synthesis, 4007-4011.
53. Weber, L. (2002) Multi-component reactions and evolutionary chemistry. Drug Discov. Today, 7, 143-147.
54. Akritopoulou-Zanze, I. (2008) Isocyanide-based multicomponent reactions in drug discovery. Curr. Opin. Chem. Bio., 12, 324-331.
55. Doenhoff, M.J., Cioli, D., and Utzinger, J. (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr. Opin. Infect. Dis., 21, 659-667.
56. Caffrey, C.R. (2007) Chemotherapy of schistosomiasis: present and future. Curr. Opin. Chem. Biol., 11, 433-439.
57. Hotez, P.J., Fenwick, A., and Kjetland, E.F. (2009) Africa's 32 cents solution for HIV/AIDS. Plos Negl. Trop. Dis., 3, e430.
58. Seubert, J., Pohlke, R., and Loebich, F. (1977) Synthesis and properties of praziquantel, a novel broad-spectrum anthelmintic with excellent activity against schistosomes and cestodes. Experientia, 33, 1036-1037.
59. D€omling, A. and Khoury, K. (2010) Praziquantel and schistosomiasis. Chem. Med. Chem., 5, 1420-1434.
60. Cao, H., Liu, H., and D€omling, A. (2010) Efficient multicomponent reaction synthesis of the schistosomiasis drug praziquantel. Chem. Eur. J., 16, 12296-12298.
61. Liu, H. and D€omling, A. (2009) Efficient and diverse synthesis of indole derivatives. J. Org. Chem., 74, 6895-6898.
62. Liu, H., William, S., Herdtweck, E., Botros, S., and Dömling, A. (2012) MCR synthesis of praziquantel derivatives. Chem. Biol. Drug Des., in press. DOI: 10.1111/j.1747-0285.2011.01288.x
63. Wang, W., Herdtweck, E., and D€omling, A. (2010) Polycyclic indole alkaloid-type compounds by MCR. Chem. Commun., 46, 770-772.
64. Wang, W., Ollio, S., Herdtweck, E., and D€omling, A. (2011) Polycyclic compounds by Ugi-Pictet-Spengler sequence. J. Org. Chem., 76, 637-644.
65. Meltzer, H.Y. and Fibiger, H.C. (1996) Olanzapine: a new atypical antipsychotic drug. Neuropsychopharmacology, 14, 83-85.
66. Bymaster, F.P., Rasmussen, K., Calligaro, D.O. et al. (1997) In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug. J. Clin. Psychiatry, 58, 28-36.
67. Kasper, S., Hale, A., Azorin, J.M., and Moller, H.J. (1999) Benefit-risk evaluation of olanzapine, risperidone and sertindole in the treatment of schizophrenia. Eur. Arch. Psych. Clin. Neurosci., 249, 2-14.
68. Chakrabarti, J.K., Hotten, T.M., and Tupper, D.E. (2012) Preparation of 2-methylthienobenzodiazepine as central nervous system agent. Application: US 5627178.
69. Huang, Y. and D€omling, A. (2011) The Gewald multicomponent reaction. Mol. Divers., 15, 3-33.
70. Shimada, O. and Yasuda, H. (1986) Hydroxyl radical scavenging action of tinoridine. Agents and Actions, 19, 208-214.
71. Walburger, A., Koul, A., Ferrari, G. et al. (2004) Protein kinase g from pathogenic mycobacteria promotes survival within macrophages. Science, 304, 1800-1804.
72. Mudumbi, R.V., Montamat, S.C., Bruns, R.F., and Vestal, R.E. (1993) Cardiac functional-responses to adenosine by pd-81723, an allosteric enhancer of the adenosine-a1-receptor. Am. J. Physiol., 264, H1017-1022.
73. Li, X.H., Conklin, D., Pan, H.L., and Eisenach, J.C. (2003) Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism. J. Pharmacol. Exp. Therap., 305, 950-955.
74. Wang, K., Kim, D.B., and D€omling, A. (2010) Cyanoacetamide MCR (III): three-component gewald reactions revisited. J. Comb. Chem., 12, 111-118.
75. Liddle, J., Allen, M.J., Borthwick, A.D. et al. (2008). The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg. Med. Chem. Lett., 18, 90-94.
76. Upreti, V.V., Soergel, D.G., and Fossler, M.J. (2007). Development, evaluation and application of a population pharmacokinetic (PPK) model for intravenously (iv) administered GSK221149A in healthy female subjects. J. Clin. Pharmacol., 47, 54.
77. Borthwick, A.D. (2010) Oral oxytocin antagonists. J. Med. Chem., 53, 6525-6538.
78. Goodwin, T.M., Valenzuela, G., Silver, H. et al. (1996) Treatment of preterm labor with the oxytocin antagonist atosiban. Am. J. Perinatol., 13, 143-146.
79. Wyatt, P.G., Allen, M.J., Borthwick, A.D. et al. (2005) 2,5-Diketopiperazines as potent and selective oxytocin antagonists. 1. Identification, stereochemistry and initial SAR. Bioorg. Med. Chem. Lett., 15, 2579-2582.
80. Borthwick, A.D., Davies, D.E., Exall, A.M. et al. (2006). 2,5-Diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 3. Synthesis, pharmacokinetics, and in vivo potency. J. Med. Chem., 49, 4159-4170.
81. Borthwick, A.D., Davies, D.E., Exall, A.M. et al. (2005) 2,5-Diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 2. Synthesis, chirality, and pharmacokinetics. J. Med. Chem., 48, 6956-6969.
82. D€omling, A. and Huang, Y. (2010) Piperazine scaffolds via isocyanide-based multicomponent reactions. Synthesis, 2859-2883.
83. Huang, Y., Khoury, K., and D€omling, A. (2010) The piperazine space in isocyanide-based mcr chemistry. Top. Heterocycl. Chem., 23, 85-127.
84. D€omling, A. (1998) Isocyanide based multi component reactions in combinatorial chemistry. Comb. Chem. High Throughput Screen., 1, 1-22.
85. Neubauer, D.N. (2010) Almorexant a dual orexin receptor antagonist for the treatment of insomnia. Curr. Opin. Investig. Drugs, 11, 101-110.
86. Aissaoui, H., Cappi, M., Clozel, M. et al. (2001) Preparation of 1,2,3,4-tetrahydroisoquinolines as orexin receptor antagonists. Application: WO 2001 068-609.
87. Stout, D.M. and Meyers, A.I. (1982) Recent advances in the chemistry of dihydropyridines. Chem. Rev., 82, 223-243.
88. Triggle, D.J. (2003) 1,4-Dihydropyridines as calcium channel ligands and privileged structures. Cell. Mol. Neurobiol., 23, 293-303.
89. Lin, J.H., Ostovic, D., and Vacca, J.P. (1998) The integration of medicinal chemistry, drug metabolism, and pharmaceutical research and development in drug discovery and development. The story of crixivan, an HIV protease inhibitor. Pharm. Biotechnol., 11, 233-255.
90. Rossen, K., Pye, P.J., Dimichele, L.M. et al. (1998) An efficient asymmetric hydrogenation approach to the synthesis of the crixivan Piperazine intermediate. Tetrahedron Lett., 39, 6823-6826.
91. Demarest, J.F., Sparks, S.S., Schell, K. et al. (2008) In vitro and clinical investigation of the relationship between ccr5 receptor occupancy and anti-HIV activity of aplaviroc. J. Clin. Pharmacol., 48, 1179-1188.
92. Nishizawa, R., Nishiyama, T., Hisaichi, K. et al. (2007). Spirodiketopiperazine-based ccr5 antagonists: lead optimization from biologically active metabolite. Bioorg. Med. Chem. Lett., 17, 727-731.
93. Mironov, M.A. (2006) Design of multi-component reactions: from libraries of compounds to libraries of reactions. QSAR Comb. Sci., 25, 423-431.
94. Ugi, I., Demharter, A., Horl, W., and Schmid, T. (1996) Ugi reactions with trifunctional [alpha]-amino acids, aldehydes, isocyanides and alcohols. Tetrahedron, 52, 11657-11664.
95. Constabel, F. and Ugi, I. (2001) Repetitive Ugi reactions. Tetrahedron, 57, 5785-5789.
96. Elders, N., Van Der Born, D., Hendrickx, L.J.D. et al. (2009) The efficient one-pot reaction of up to eight components by the union of multicomponent reactions. Angew. Chem. Int. Ed., 48, 5856-5859.
97. Al-Tel, T.H., Al-Qawasmeh, R.A., and Voelter, W. (2010) Rapid assembly of polyfunctional structures using a one-pot five-and six-component sequential Groebke-Blackburn/Ugi/Passerini process. Eur. J. Org. Chem., 29, 5586-5593.
98. Brauch, S., Gabriel, L., and Westermann, B. (2010) Seven-component reactions by sequential chemoselective Ugi-Mumm/Ugi-Smiles reactions. Chem. Commun., 46, 3387-3389.
99. Portlock, D.E., Naskar, D., West, L. et al. (2003) Solid-phase synthesis of five-dimensional libraries via a tandem Petasis-Ugi multi-component condensation reaction. Tetrahedron Lett., 44, 5121-5124.
100. Portlock, D.E., Ostaszewski, R., Naskar, D., and West, L. (2003) A tandem Petasis-Ugi multi component condensation reaction: solution phase synthesis of six dimensional libraries. Tetrahedron Lett., 44, 603-605.
101. Haswell, S.J. and Watts, P. (2003) Green chemistry: synthesis in micro reactors. Green Chem., 5, 240-249. [100] Mason, B.P., Price, K.E., Steinbacher, J.L. et al. (2007) Greener approaches to organic synthesis using microreactor technology. Chem. Rev., 107, 2300-2318.
102. Cukalovic, A., Monbaliu, J.-C.M.R., and Stevens, C.V. (2010) Microreactor technology as an efficient tool for multicomponent reactions. Top. Heterocycl. Chem., 23, 161-198.
103. Mitchell, M.C., Spikmans, V., and Mello, A.J.D. (2001) Microchip-based synthesis and analysis: control of multicomponent reaction products and intermediates. Analyst, 126, 24-27.
104. Demello, A.J. (2006) Control and detection of chemical reactions in microfluidic systems. Nature, 442, 394-402.
105. Dubois, P., Marchand, G., Fouillet, Y. et al. (2006) Ionic liquid droplet as e-microreactor. Anal. Chem., 78, 4909-4917.
106. Jas, G. and Kirschning, A. (2003) Continuous flow techniques in organic synthesis. Chem. Eur. J., 9, 5708-5723.
107. Bremner, W.S. and Organ, M.G. (2006) Multicomponent reactions to form heterocycles by microwave-assisted continuous flow organic synthesis. J. Comb. Chem., 9, 14-16.
108. Desimone, J.M. (2002) Practical approaches to green solvents. Science, 297, 799-803.
109. Bosch, M.E., Sanchez, A.J.R., Rojas, F.S., and Ojeda, C.B. (2009) Applications of supercritical fluid chromatography-tandem mass spectrometry in pharmaceuticals. Curr. Drug Discov. Technol., 6, 214-229.
110. Schwerkoske, J., Masquelin, T., Perun, T., and Hulme, C. (2005) New multi-component reaction accessing 3-aminoimidazo[1,2-a]pyridines. Tetrahedron Lett., 46, 8355-8357.
111. Imperato, G., Konig, B., and Chiappe, C. (2007) Ionic green solvents from renewable resources. Eur. J. Org. Chem., 1049-1058.
112. Isambert, N., Duque, M.D.M.S., Plaquevent, J.-C. et al. (2011) Multicomponent reactions and ionic liquids: a perfect synergy for eco-compatible heterocyclic synthesis. Chem. Soc. Rev., 40, 1347-1357.
113. Feng, L.C., Sun, Y.W., Tang, W.J. et al. (2010) Highly efficient chemoselective construction of 2,2-dimethyl-6-substituted 4-piperidones via multi-component tandem Mannich reaction in ionic liquids. Green Chem., 12, 949-952.
114. Zhang, W. (2009) Green chemistry aspects of fluorous techniques-opportunities and challenges for small-scale organic synthesis. Green Chem., 11, 911-920.
115. Zhang, W. (2007) Fluorous-enhanced multicomponent reactions for making drug-like library scaffolds. Comb. Chem. High Throughput Screen., 10, 219-229.
116. Liu, A.F., Zhou, H.Y., Su, G.X. et al. (2009) Microwave-assisted fluorous synthesis of a 1,4-benzodiazepine-2,5-dione library. J. Comb. Chem., 11, 1083-1093.
117. Wender, P.A., Handy, S.T., and Wright, D.L. (1997) Towards the ideal synthesis. Chem. Ind., 765-774.