[en] Despite extensive research into peptide synthesis, coupling of amino acids with weakly nucleophilic heterocyclic amines remains a challenge. The need for microwave technology to promote this coupling interferes with the scalability of the process. By applying the microwave-to-flow paradigm, a library of (α-aminoacyl)amino-substituted heterocycles was continuously produced at near quantitative conversions and the reaction was scaled up successfully. Various N-Cbz-protected amino acids were activated using BtH/SOCl2 under continuous-flow conditions with excellent yields. Their coupling with heterocyclic amines was accomplished in MeCN—NMP on a preparative scale. However, performing both steps in-line resulted in an inconvenient work-up. Therefore, a two-step approach was taken, isolating the intermediate Bt-activated amino acid via simple filtration. This allows for a solvent switch to DMSO for the coupling reaction which led to excellent conversions for a broad range of substrates.
Disciplines :
Chemistry
Author, co-author :
Seghers, Sofie; Ghent University > Department of Sustainable Organic Chemistry and Technology
Van Waes, Frederik E. A.; Ghent University > Department of Sustainable Organic Chemistry and Technology
Cukalovic, Ana; Ghent University > Department of Sustainable Organic Chemistry and Technology
Monbaliu, Jean-Christophe ; Université de Liège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis
De Visscher, Jeroen; Ghent University > Department of Sustainable Organic Chemistry and Technology
Thybaut, Joris; Ghent University > Department of Chemical Engineering and Technical Chemistry
Heugebaert, Thomas S.A.; Ghent University > Department of Sustainable Organic Chemistry and Technology
Stevedns, Christian V.; Ghent University > Department of Sustainable Organic Chemistry and Technology
Language :
English
Title :
Efficient Continuous Flow Benzotriazole Activation and Coupling of Amino Acids
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Bibliography
(a) Grauer, A.; Konig, B. Eur. J. Org. Chem. 2009, 5099-5111;
(c) Vagner, J.; Qu, H. C.; Hruby, V. J. Curr. Opin. Chem. Biol. 2008, 12, 292-296.
Okandeji, B. O.; Greenwald, D. M.; Wroten, J.; Sello, J. K. Bioorg. Med. Chem. 2011, 19, 7679-7689.
Shi, W.; Ma, H. K.; Duan, Y. J.; Aubart, K.; Fang, Y. H.; Zonis, R.; Yang, L. P.; Hu, W. H., Bioorg. Med. Chem. Lett. 2011, 21, 1060-1063.
Lee, J.; Bae, S.; Lee, S. H.; Choi, H.; Kim, Y. H.; Kim, S. J.; Park, G. T.; Moon, S. K.; Kim, D. H.; Lee, S.; Ahn, S. K.; Choi, N. S.; Lee, K. J. Bioorg. Med. Chem. Lett. 2010, 20, 6327-6330.
(a) Crisostomo, F. R. P.; Feng, Y. M.; Zhu, X. J.; Welsh, K.; An, J.; Reed, J. C.; Huang, Z. W. Bioorg. Med. Chem. Lett. 2009, 19, 6413-6418;
(b) Zobel, K.; Wang, L.; Varfolomeev, E.; Franklin, M. C.; Elliott, L. O.; Wallweber, H. J. A.; Okawa, D. C.; Flygare, J. A.; Vucic, D.; Fairbrother, W. J.; Deshayes, K. ACS Chem. Biol. 2006, 1, 525-534.
(a) Hinkle, C. L.; Mohan, M. J.; Lin, P. Y.; Yeung, N.; Rasmussen, F.; Milla, M. E.; Moss, M. L. Biochemistry 2003, 42, 2127-2136;
(b) Rabinowitz, M. H.; Andrews, R. C.; Becherer, J. D.; Bickett, D. M.; Bubacz, D. G.; Conway, J. G.; Cowan, D. J.; Gaul, M.; Glennon, K.; Lambert, M. H.; Leesnitzer, M. A.; McDougald, D. L.; Moss, M. L.; Musso, D. L.; Rizzolio, M. C. J. Med. Chem. 2001, 44, 4252-4267.
Duflos, M.; Courant, J.; Le Baut, G.; Grimaud, N.; Renard, P.; Manechez, D.; Caignard, D. H. Eur. J. Med. Chem. 1998, 33, 635-645.
Altman, J.; Gorecki, M.; Wilchek, M.; Votano, J. R.; Rich, A. J. Med. Chem. 1984, 27, 596-600.
Schnatterer, S.; Hawkins, D. W.; Jans, D.; Maier, M.; Kuhlmann, A.; Sanwald, E. F.; Thoenessen, M.-T.; Seeger, K. (Bayer Cropscience S. A., Fr) Preparation of pesticidal 5-(acylamino) pyrazole derivatives. WO 2004049803 A1, Jun. 17, 2004.
Braxmeier, T.; Demarcus, M.; Fessmann, T.; McAteer, S.; Kilburn, J. D. Chem. Eur. J. 2001, 7, 1889-1898.
(a) Katritzky, A. R.; Lan, X. F.; Yang, J. Z.; Denisko, O. V. Chem. Rev. 1998, 98, 409-548;
(b) Panda, S. S.; Hall, C. D.; Scriven, E.; Katritzky, A. R. Aldrichimica Acta 2013, 46, 43-55.
(a) Katritzky, A. R.; Abo-Dya, N. E.; Tala, S. R.; Gyanda, K.; Abdel-Samii, Z. K. Org. Biomol. Chem. 2009, 7, 4444-4447;
(b) Katritzky, A. R.; Angrish, P.; Todadze, E. Synlett 2009, 2392-2411;
(c) Katritzky, A. R.; Narindoshvili, T.; Draghici, B.; Angrish, P. J. Org. Chem. 2008, 73, 511-516;
(d) Katritzky, A. R.; Rachwal, S. Chem. Rev. 2010, 110, 1564-1610;
(e) Katritzky, A. R.; Rachwal, S. Chem. Rev. 2011, 111, 7063-7120;
(f) Katritzky, A. R.; Zhang, Y. M.; Singh, S. K. Synthesis 2003, 2795-2798;
(g) Katritzky, A. R.; Rogovoy, B. V. Chem. Eur. J. 2003, 9, 4586-4593.
Katritzky, A. R.; El-Gendy, B.; Todadze, E.; Abdel-Fattah, A. A. A. J. Org. Chem. 2008, 73, 5442-5445.
Quelever, G.; Burlet, S.; Garino, C.; Pietrancosta, N.; Laras, Y.; Kraus, J. L. J. Comb. Chem. 2004, 6, 695-698.
Leadbeater, N. E., Microwave Heating as a Tool for Sustainable Chemistry. CRC Press: Boca Raton, 2010; p 290.
Glasnov, T. N.; Kappe, C. O. Chem. Eur. J. 2011, 17, 11956-11968.
(a) Acke, D. R. J.; Stevens, C. V. Green Chemistry 2007, 9, 386-390;
(b) Cukalovic, A.; Monbaliu, J.-C. R.; Stevens, C. Microreactor Technology as an Efficient Tool for Multicomponent Reactions. In Synthesis of Heterocycles via Multicomponent Reactions I; Orru, R. V. A.; Ruijter, E., Eds.; Springer: Berlin, Heidelberg, 2010; Vol. 23, pp 161-198;
(c) Heugebaert, T. S.; Stevens, C. V.; Kappe, C. O. ChemSusChem 2015, 8, 1648-1651;
(d) Van Waes, F. E. A.; Drabowicz, J.; Cukalovic, A.; Stevens, C. V. Green Chem. 2012, 14, 2776-2779;
(e) Van Waes, F. E. A.; Seghers, S.; Dermaut, W.; Cappuyns, B.; Stevens, C. V. J. Flow Chem. 2014, 4, 118-124.
(a) Watts, P.; Wiles, C.; Haswell, S. J.; Pombo-Villar, E. Tetrahedron 2002, 58, 5427-5439;
(b) Watts, P.; Wiles, C.; Haswell, S. J.; Pombo-Villar, E.; Styring, P. Chem. Commun. 2001, 990-991;
(c) Wiles, C.; Ngamsom, B. Continuous Flow Synthesis of β-Peptides within Labtrix® Micro Reactors 2010 (accessed Jan 07, 2015).
Flogel, O.; Codee, J. D. C.; Seebach, D.; Seeberger, P. H. Angew. Chem., Int. Ed. 2006, 45, 7000-7003.
Baxendale, I. R.; Ley, S. V.; Smith, C. D.; Tranmer, G. K. Chem. Commun. 2006, (46), 4835-4837.
Mandity, I. M.; Olasz, B.; Otvos, S. B.; Fülöp, F. ChemSusChem 2014, 7, 3172-3176.
(a) Katritzky, A. R.; Angrish, P. Steroids 2006, 71, 660-669;
(b) Katritzky, A. R.; Angrish, P.; Suzuki, K. Synthesis 2006, 411-424;
(c) Katritzky, A. R.; Suzuki, K.; Singh, S. K. Synthesis 2004, 2645-2652;
(d) Katritzky, A. R.; Todadze, E.; Cusido, J.; Angrish, P.; Shestopalov, A. A. Chem. Biol. Drug. Des. 2006, 68, 37-41;
(e) Katritzky, A. R.; Vincek, A. S.; Suzuki, K. Arkivoc 2005, 116-126.
Katritzky, A. R.; He, H. Y.; Suzuki, K. J. Org. Chem. 2000, 65, 8210-8213.
Katritzky, A. R.; Wang, M. Y.; Yang, H. F.; Zhang, S. M.; Akhmedov, N. G. Arkivoc 2002, 134-142.
Katritzky, A. R.; Angrish, P.; Hur, D.; Suzuki, K. Synthesis 2005, 397-402.
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