Login Register Cart 0
Generic placeholder image

Current Chinese Science

Editor-in-Chief

ISSN (Print): 2210-2981
ISSN (Online): 2210-2914

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Research Article Section: Biochemistry

Microwave Assisted Aza-michael Additions Towards β-amino Acids

Author(s): Fan Yinqi and Matziari Magdalini*

Volume 3, Issue 3, 2023

Published on: 03 February, 2023

Page: [166 - 177] Pages: 12

DOI: 10.2174/2210298103666230120114302

Price: $65

Abstract

Background: β-amino acids are non-natural amino acids, where the amino group is attached to the β-carbon instead of the α-carbon. Peptides containing β-amino acids present with particular secondary structures and remarkable chemical and biological properties. β-peptides are used as peptidomimetics, based on the resistance to hydrolysis in vivo, with various important applications in the field of Medicine.

Methods: Several synthetic methods have appeared in recent years, with the Aza- Michael conjugate addition reactions, being a very effective approach towards β-amino acids. Microwave irradiation mediated reactions have also attracted much interest since they significantly improve the reaction yields while reducing the reaction time and avoiding by-products formation. The aim of this project has been the development of a reliable and general synthetic methodology towards β2 and β3 amino acids with the use of conjugate additions of N-nucleophiles to substituted acrylate derivatives. The application of effective catalysts has been also examined here.

Results: The results show that the acrylate precursors of β2 and β3 amino acids with side chains corresponding to Phe, Asp, Ile, Leu, Val, and Tyr have been synthesized successfully by using a one-pot Horner-Wadsworth-Emmons reaction, and they have been used for the addition of Nnucleophiles, with a study on conditions and yields optimization.

Conclusion: With the main challenge for β-amino acid synthesis being that there is still no general method to synthesize different types of β-amino acids corresponding to all-natural α-amino acids, the proposed synthetic methodology may offer this possibility.

Keywords: β-amino acids, peptidomimetics, michael addition, microwave irradiation, horner-wadsworth-emmons reaction, acrylates.

« Previous Next »
Graphical Abstract

[1]
Kiss, L.; Nonn, M.; Forró, E.; Sillanpää, R.; Fustero, S.; Fülöp, F. A selective synthesis of fluorinated cispentacin derivatives. Eur. J. Org. Chem., 2014, 2014(19), 4070-4076.
[http://dx.doi.org/10.1002/ejoc.201402121]
[2]
Sorbera, L.A.; Castañer, J.; Bozzo, J. PLD-118: Antifungal isoleucyl-tRNA synthetase inhibitor. Drugs Future, 2002, 27(11), 1049-1055.
[http://dx.doi.org/10.1358/dof.2002.027.11.707984]
[3]
Petraitiene, R.; Petraitis, V.; Kelaher, A.M.; Sarafandi, A.A.; Mickiene, D.; Groll, A.H.; Sein, T.; Bacher, J.; Walsh, T.J. Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits. Antimicrob. Agents Chemother., 2005, 49(5), 2084-2092.
[http://dx.doi.org/10.1128/AAC.49.5.2084-2092.2005] [PMID: 15855534]
[4]
Goto, T.; Toya, Y.; Kondo, T. Structure of amipurimycin, a new nucleoside antibiotic produced by Streptomyces novoguineensis. Nucleic Acids Symp. Ser., 1980, 8(8), s73-s74.
[PMID: 7255201]
[5]
Hashimoto, T.; Kondo, S.; Naganawa, H.; Takita, T.; Maeda, K.; Umezawa, H. Letter: The abolute structure of oryzoxymycin. J. Antibiot., 1974, 27(1), 86-87.
[http://dx.doi.org/10.7164/antibiotics.27.86] [PMID: 4843052]
[6]
Harada, S.; Kishi, T. Isolation and characterization of a new nucleoside antibiotic, amipurimycin. J. Antibiot., 1977, 30(1), 11-16.
[http://dx.doi.org/10.7164/antibiotics.30.11] [PMID: 838627]
[7]
Seebach, D.; Gardiner, J. β-Peptidic peptidomimetics. Acc. Chem. Res., 2008, 41(10), 1366-1375.
[http://dx.doi.org/10.1021/ar700263g] [PMID: 18578513]
[8]
Seebach, D.; Gademann, K.; Schreiber, J.V.; Matthews, J.L.; Hintermann, T.; Jaun, B.; Oberer, L.; Hommel, U.; Widmer, H. ‘Mixed’ β-peptides: A unique helical secondary structure in solution. Preliminary communication. Helv. Chim. Acta, 1997, 80(7), 2033-2038.
[http://dx.doi.org/10.1002/hlca.19970800703]
[9]
Weiss, H.M.; Wirz, B.; Schweitzer, A.; Amstutz, R.; Perez, M.I.R.; Andres, H.; Metz, Y.; Gardiner, J.; Seebach, D. ADME investigations of unnatural peptides: Distribution of a 14C-labeled β 3-octaarginine in rats. Chem. Biodivers., 2007, 4(7), 1413-1437.
[http://dx.doi.org/10.1002/cbdv.200790121] [PMID: 17638323]
[10]
Stoeckli, M.; Staab, D.; Schweitzer, A.; Gardiner, J.; Seebach, D. Imaging of a β -peptide distribution in whole-body mice sections by MALDI mass spectrometry. J. Am. Soc. Mass Spectrom., 2007, 18(11), 1921-1924.
[http://dx.doi.org/10.1016/j.jasms.2007.08.005] [PMID: 17827032]
[11]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 1997, 23(1), 3-25.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[12]
Lipinski, C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 235-249.
[http://dx.doi.org/10.1016/S1056-8719(00)00107-6] [PMID: 11274893]
[13]
Craik, D.J.; Fairlie, D.P.; Liras, S.; Price, D. The future of peptide-based drugs. Chem. Biol. Drug Des., 2013, 81(1), 136-147.
[http://dx.doi.org/10.1111/cbdd.12055] [PMID: 23253135]
[14]
Bidwell, G.L. Peptides for cancer therapy: A drug-development opportunity and a drug-delivery challenge. Ther. Deliv., 2012, 3(5), 609-621.
[http://dx.doi.org/10.4155/tde.12.37] [PMID: 22834405]
[15]
Arslan, E.; Garip, I.C.; Gulseren, G.; Tekinay, A.B.; Guler, M.O. Bioactive supramolecular peptide nanofibers for regenerative medicine. Adv. Healthc. Mater., 2014, 3(9), 1357-1376.
[http://dx.doi.org/10.1002/adhm.201300491] [PMID: 24574311]
[16]
Cai, C.; Lin, J.; Lu, Y.; Zhang, Q.; Wang, L. Polypeptide self-assemblies: Nanostructures and bioapplications. Chem. Soc. Rev., 2016, 45(21), 5985-6012.
[http://dx.doi.org/10.1039/C6CS00013D] [PMID: 27722321]
[17]
Hejčl, A.; Lesný, P.; Přádný, M.; Michálek, J.; Jendelová, P.; Štulík, J.; Syková, E. Biocompatible hydrogels in spinal cord injury repair. Physiol. Res., 2008, 57(S3), S121-S132.
[http://dx.doi.org/10.33549/physiolres.931606] [PMID: 18481908]
[18]
Cheng, R.P.; Gellman, S.H.; DeGrado, W.F. beta-Peptides: From structure to function. Chem. Rev., 2001, 101(10), 3219-3232.
[http://dx.doi.org/10.1021/cr000045i] [PMID: 11710070]
[19]
Luder, K.; Kulkarni, K.; Lee, H.W.; Widdop, R.E.; Del Borgo, M.P.; Aguilar, M.I. Decorated self-assembling β3-tripeptide foldamers form cell adhesive scaffolds. Chem. Commun., 2016, 52(24), 4549-4552.
[http://dx.doi.org/10.1039/C6CC00247A] [PMID: 26940541]
[20]
Motamed, S.; Del Borgo, M.P.; Kulkarni, K.; Habila, N.; Zhou, K.; Perlmutter, P.; Forsythe, J.S.; Aguilar, M.I. A self-assembling β-peptide hydrogel for neural tissue engineering. Soft Matter, 2016, 12(8), 2243-2246.
[http://dx.doi.org/10.1039/C5SM02902C] [PMID: 26853859]
[21]
Mangelschots, J.; Bibian, M.; Gardiner, J.; Waddington, L.; Van Wanseele, Y.; Van Eeckhaut, A.; Acevedo, M.M.D.; Van Mele, B.; Madder, A.; Hoogenboom, R.; Ballet, S. Mixed α/β-peptides as a class of short amphipathic peptide hydrogelators with enhanced proteolytic stability. Biomacromolecules, 2016, 17(2), 437-445.
[http://dx.doi.org/10.1021/acs.biomac.5b01319] [PMID: 26741458]
[22]
Goel, R.; Sharma, A.K.; Gupta, A. Self-assembled amphiphilic mixed α/β-tetrapeptoid nanostructures as promising drug delivery vehicles. New J. Chem., 2017, 41(6), 2340-2348.
[http://dx.doi.org/10.1039/C6NJ03281H]
[23]
Arend, M.; Westermann, B.; Risch, N. Modern variants of the mannich reaction. Angew. Chem. Int. Ed., 1998, 37(8), 1044-1070.
[http://dx.doi.org/10.1002/(SICI)1521-3773(19980504)37:8<1044::AID-ANIE1044>3.0.CO;2-E] [PMID: 29711029]
[24]
Lin, Y.; Junhua, Z.; Huangshu, L.; Qilin, H. The mannich reaction of butanone, aromatic aldehydes and aromatic amines. Synth. Commun., 1991, 21(20), 2109-2117.
[http://dx.doi.org/10.1080/00397919108019818]
[25]
Tramontini, M.; Angiolini, L. Further advances in the chemistry of mannich bases. Tetrahedron, 1990, 46(6), 1791-1837.
[http://dx.doi.org/10.1016/S0040-4020(01)89752-0]
[26]
Meth, C.O.; Stanforth, S.P. 3.5-The vilsmeier-haack reaction. In: Comprehensive Organic Synthesis; Pergamon: Oxford, 1991; Vol. 2, pp. 777-794.
[http://dx.doi.org/10.1016/B978-0-08-052349-1.00049-4]
[27]
Romanens, A.; Bélanger, G. Preparation of conformationally restricted β(2,2)- and β(2,2,3)-amino esters and derivatives containing an all-carbon quaternary center. Org. Lett., 2015, 17(2), 322-325.
[http://dx.doi.org/10.1021/ol503432b] [PMID: 25551418]
[28]
Nelson, S.G. Catalyzed enantioselective aldol additions of latent enolate equivalents. Tetrahedron Asymmetry, 1998, 9(3), 357-389.
[http://dx.doi.org/10.1016/S0957-4166(97)00634-4]
[29]
Hatano, M.; Takagi, E.; Ishihara, K. Sodium phenoxide-phosphine oxides as extremely active Lewis base catalysts for the Mukaiyama aldol reaction with ketones. Org. Lett., 2007, 9(22), 4527-4530.
[http://dx.doi.org/10.1021/ol702052r] [PMID: 17894505]
[30]
Rulev, A.Y. Aza-Michael reaction: Achievements and prospects. Russ. Chem. Rev., 2011, 80(3), 197-218.
[http://dx.doi.org/10.1070/RC2011v080n03ABEH004162]
[31]
Jenner, G. Catalytic high pressure synthesis of hindered β-aminoesters. Tetrahedron Lett., 1995, 36(2), 233-236.
[http://dx.doi.org/10.1016/0040-4039(94)02215-W]
[32]
Xu, L.W.; Xia, C.G.; Hu, X.X. An efficient and inexpensive catalyst system for the aza-Michael reactions of enones with carbamates. Chem. Commun., 2003, (20), 2570-2571.
[http://dx.doi.org/10.1039/b307733k] [PMID: 14594285]
[33]
Kobayashi, S.; Kakumoto, K.; Sugiura, M. Transition metal salts-catalyzed aza-Michael reactions of enones with carbamates. Org. Lett., 2002, 4(8), 1319-1322.
[http://dx.doi.org/10.1021/ol0256163] [PMID: 11950352]
[34]
Carlqvist, P.; Svedendahl, M.; Branneby, C.; Hult, K.; Brinck, T.; Berglund, P. Exploring the active-site of a rationally redesigned lipase for catalysis of Michael-type additions. ChemBioChem, 2005, 6(2), 331-336.
[http://dx.doi.org/10.1002/cbic.200400213] [PMID: 15578634]
[35]
Wabnitz, T.C.; Spencer, J.B. A general, Brønsted acid-catalyzed hetero-Michael addition of nitrogen, oxygen, and sulfur nucleophiles. Org. Lett., 2003, 5(12), 2141-2144.
[http://dx.doi.org/10.1021/ol034596h] [PMID: 12790549]
[36]
Shuter, E.C.; Duong, H.; Hutton, C.A.; McLeod, M.D. The enantioselective synthesis of APTO and AETD: Polyhydroxylated β-amino acid constituents of the microsclerodermin cyclic peptides. Org. Biomol. Chem., 2007, 5(19), 3183-3189.
[http://dx.doi.org/10.1039/b707891a] [PMID: 17878977]
[37]
Steinreiber, A.; Stadler, A.; Mayer, S.F.; Faber, K.; Kappe, C.O. High-speed microwave-promoted Mitsunobu inversions. Application toward the deracemization of sulcatol. Tetrahedron Lett., 2001, 42(36), 6283-6286.
[http://dx.doi.org/10.1016/S0040-4039(01)01248-5]
[38]
Amore, K.M.; Leadbeater, N.E.; Miller, T.A.; Schmink, J.R. Fast, easy, solvent-free, microwave-promoted Michael addition of anilines to α,β-unsaturated alkenes: Synthesis of N-aryl functionalized β-amino esters and acids. Tetrahedron Lett., 2006, 47(48), 8583-8586.
[http://dx.doi.org/10.1016/j.tetlet.2006.09.114]
[39]
Escalante, J.; Carrillo-Morales, M.; Linzaga, I. Michael additions of amines to methyl acrylates promoted by microwave irradiation. Molecules, 2008, 13(2), 340-347.
[http://dx.doi.org/10.3390/molecules13020340] [PMID: 18305422]
[40]
Matziari, M.; Xie, Y. One-pot synthesis of α-substituted acrylates. SynOpen, 2018, 2(2), 0161-0167.
[http://dx.doi.org/10.1055/s-0037-1610357]
[41]
Kalita, D.J.; Borah, R.; Sarma, J.C. A new selective catalytic acetalization method promoted by microwave irradiation. Tetrahedron Lett., 1998, 39(25), 4573-4574.
[http://dx.doi.org/10.1016/S0040-4039(98)00809-0]

Rights & Permissions Print Cite
Article Metrics
21
2
© 2024 Bentham Science Publishers | Privacy Policy