Methods for synthesizing hydroxamic acids and their metal complexes

Ibrahima Sory Sow

doi:10.5155/eurjchem.15.4.345-354.2565

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Published: Dec 31, 2024

DOI: https://doi.org/10.5155/eurjchem.15.4.345-354.2565

Keywords:

Synthetic route, Carboxylic acid, Hydroxylamine, Optimal method, Hydroxamic acid, Metallic complex

Section

Review Article

Issue

Vol. 15 No. 4 (2024): December 2024

Dates

Received 2024-05-19
Accepted 2024-10-08
Published 2024-12-31

Ibrahima Sory Sow

Microbiology, Bioorganic and Macromolecular Chemistry Unit, Faculty of Pharmacy, Université libre de Bruxelles (ULB), 1050 Brussels, Belgium

https://orcid.org/0000-0003-4038-7927

Abstract

In previously published works, the antibacterial, antifungal, antimycobacterial and anticancer activities of hydroxamic acids (HA) and their complexes were reported. Our recently published work shows that aliphatic HA with a number of carbon atoms equal to 12 (C₁₂) and its Fe(II), Fe(III), Ni(II), Cu(II) and Zn(II) complexes are significantly active against bacteria (Staphylococcus aureus, Escherichia coli), fungal (Candida albicans) and mycobacteria (Mycobacterium smegmatis). Furthermore, the inhibitory activities against biofilms of Mycobacterium tuberculosis, Mycobacterium bovis BCG, Mycobacterium marinum and Pseudomonas aeruginosa were observed with a large number of HA and their complexes. Suberoylanilide HA and resminostat were approved to treat cutaneous T cell lymphoma and in clinical trials to treat advanced hepatocellular carcinoma, respectively. In view of the interesting biological properties of this family of chemical compounds, the synthesis of HA has been reported in numerous research articles in recent years but this is the second review article dedicated to their synthetic methods and the first review for their complexes. The aim of this review is to highlight optimal and rational methods for the synthesis of HA and their complexes. HA are obtained in near-quantitative yields from carboxylic acid, ethyl chloroformate, N-methylmorpholine and hydroxylamine. As for their complexes, the synthesis methods described are fairly similar and would all appear to be optimal. The main criteria are the number of equivalents of HA, the type of metal salt or solvent used and the reaction conditions.

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Sow, I. S. Methods for Synthesizing Hydroxamic Acids and Their Metal Complexes. Eur. J. Chem. 2024, 15, 345-354.

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References

[1]. Agrawal, M. A.; Harjit, J.; Pande, R. Determination of physical parameters of weak organic bases: hydroxamic acids. J. Phys. Org. Chem. 1999, 12, 103-108.
https://doi.org/10.1002/(SICI)1099-1395(199902)12:2<103::AID-POC99>3.0.CO;2-L

[2]. Muri, E. M. F.; Nieto, M. J.; Williamson, J. S. Hydroxamic acids as pharmacological agents: An update. Med. Chem. Rev. 2004, 1, 385-394.
https://doi.org/10.2174/1567203043401572

[3]. Alam, M. A. Methods for hydroxamic acid synthesis. Curr. Org. Chem. 2019, 23, 978-993.
https://doi.org/10.2174/1385272823666190424142821

[4]. Hydroxamic acids: A unique family of chemicals with multiple biological activities; Gupta, S. P., Ed.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2013.

[5]. Maehr, H. Antibiotics and other naturally occurring hydroxamic acids and hydroxamates. Pure Appl. Chem. 1971, 28, 603-636.
https://doi.org/10.1351/pac197128040603

[6]. Das, M.; Das, B.; Samanta, A. Antioxidant and anticancer activity of synthesized 4-amino-5-((aryl substituted)-4H-1,2,4-triazole-3-yl)thio-linked hydroxamic acid derivatives. J. Pharm. Pharmacol. 2019, 71, 1400-1411.
https://doi.org/10.1111/jphp.13131

[7]. Pal, D.; Saha, S. Hydroxamic acid - A novel molecule for anticancer therapy. J. Adv. Pharm. Technol. Res. 2012, 3, 92-99.
https://doi.org/10.4103/2231-4040.97281

[8]. Saban, N.; Bujak, M. Hydroxyurea and hydroxamic acid derivatives as antitumor drugs. Cancer Chemother. Pharmacol. 2009, 64, 213-221.
https://doi.org/10.1007/s00280-009-0991-z

[9]. Bertrand, S.; Hélesbeux, J.-J.; Larcher, G.; Duval, O. Hydroxamate, a key pharmacophore exhibiting a wide range of biological activities. Mini Rev. Med. Chem. 2013, 13, 1311-1326.
https://doi.org/10.2174/13895575113139990007

[10]. Gonçalves, B. L.; Ramos, D. F.; Halicki, P. C. B.; da Silva, P. E. A.; Vicenti, J. R. de M. Synthesis, modeling and biological activity of new zinc(II) hydroxamates against streptococcus pneumoniae. Chem. Data Coll. 2019, 22, 100240.
https://doi.org/10.1016/j.cdc.2019.100240

[11]. Sumrra, S. H.; Zafar, W.; Imran, M.; Chohan, Z. H. A review on the biomedical efficacy of transition metal triazole compounds. J. Coord. Chem. 2022, 75, 293-334.
https://doi.org/10.1080/00958972.2022.2059359

[12]. Amjad, M.; Sumrra, S. H.; Akram, M. S.; Chohan, Z. H. Metal-based ethanolamine-derived compounds: a note on their synthesis, characterization and bioactivity. J. Enzyme Inhib. Med. Chem. 2016, 31, 88-97.
https://doi.org/10.1080/14756366.2016.1220375

[13]. Keogan, D. M.; Oliveira, S. S. C.; Sangenito, L. S.; Branquinha, M. H.; Jagoo, R. D.; Twamley, B.; Santos, A. L. S.; Griffith, D. M. Novel antimony(iii) hydroxamic acid complexes as potential anti-leishmanial agents. Dalton Trans. 2018, 47, 7245-7255.
https://doi.org/10.1039/C8DT00546J

[14]. Failes, T. W.; Hambley, T. W. Crystal structures of Tris(hydroxamato) complexes of iron(III). Aust. J. Chem. 2000, 53, 879-881.
https://doi.org/10.1071/CH00118

[15]. McSweeney, C. C.; Hutchinson, S.; Harris, S.; Glennon, J. D. Supercritical fluid chromatography and extraction of Fe(III) with hydroxamic acids. Anal. Chim. Acta 1997, 346, 93-99.
https://doi.org/10.1016/S0003-2670(97)00240-7

[16]. Sow, I. S.; Gelbcke, M.; Meyer, F.; Vandeput, M.; Marloye, M.; Basov, S.; Van Bael, M. J.; Berger, G.; Robeyns, K.; Hermans, S.; Yang, D.; Fontaine, V.; Dufrasne, F. Synthesis and biological activity of iron(II), iron(III), nickel(II), copper(II) and zinc(II) complexes of aliphatic hydroxamic acids. J. Coord. Chem. 2023, 76, 76-105.
https://doi.org/10.1080/00958972.2023.2166407

[17]. Yang, D.; Zhang, Y.; Sow, I. S.; Liang, H.; El Manssouri, N.; Gelbcke, M.; Dong, L.; Chen, G.; Dufrasne, F.; Fontaine, V.; Li, R. Antimycobacterial activities of hydroxamic acids and their iron(II/III), nickel(II), copper(II) and zinc(II) complexes. Microorganisms 2023, 11, 2611-2622.
https://doi.org/10.3390/microorganisms11102611

[18]. Bayer, E. Soluble iron(III)-hydroxamic acid complexes. WO1229, 1967, Appl. No. PCT/CH 440314.

[19]. Brown, D. A.; Glass, W. K.; McGardle, S. J. C. Monohydroxamic acid complexes of iron(II and III), cobalt(II and III), copper(II) and zinc(II). Inorganica Chim. Acta 1983, 80, 13-18.
https://doi.org/10.1016/S0020-1693(00)91255-6

[20]. Griffith, D. M.; Szőcs, B.; Keogh, T.; Suponitsky, K. Y.; Farkas, E.; Buglyó, P.; Marmion, C. J. Suberoylanilide hydroxamic acid, a potent histone deacetylase inhibitor; its X-ray crystal structure and solid state and solution studies of its Zn(II), Ni(II), Cu(II) and Fe(III) complexes. J. Inorg. Biochem. 2011, 105, 763-769.
https://doi.org/10.1016/j.jinorgbio.2011.03.003

[21]. Shankar, B.; Tomar, R.; Kumar, R.; Godhara, M.; Sharma, V.K. Antimicrobial activity of newly synthesized hydroxamic acid of pyrimidine-5-carboxylic acid and its complexes with Cu(II), Ni(II), Co(II) and Zn(II) metal ions. J. Chem. Pharm. Res. 2014, 6, 925-930. https://www.jocpr.com/articles/antimicrobial-activity-of-newly-synthesized-hydroxamic-acid-of-pyrimidine5carboxylic-acid-and-its-complexes-with-cuii-ni.pdf (accessed May 5, 2024).

[22]. Sukumar, S.; Subba Rao, R. V.; Natarajan, R. Improved preparation of acetohydroxamic acid. Org. Prep. Proced. Int. 2014, 46, 85-87.
https://doi.org/10.1080/00304948.2014.866477

[23]. Olah, G. A.; Vankar, Y. D. Synthetic methods and reactions; 521. Preparation of nitriles from aldoximes via dehydration with trimethylamine/sulfur dioxide complex. Synthesis 1978, 1978, 702-703.
https://doi.org/10.1055/s-1978-24867

[24]. Sosnovsky, G.; Krogh, J. A. A new method for the preparation of aliphatic hydroxamic acids; Reaction of primary nitroalkanes with selenium dioxide in the presence of triethylamine. Synthesis 1980, 1980, 654-656.
https://doi.org/10.1055/s-1980-29158

[25]. Bailén, M. A.; Chinchilla, R.; Dodsworth, D. J.; Nájera, C. Direct synthesis of hydroxamates from carboxylic acids using 2-mercaptopyridone-1-oxide-based thiouronium salts. Tetrahedron Lett. 2001, 42, 5013-5016.
https://doi.org/10.1016/S0040-4039(01)00923-6

[26]. Giacomelli, G.; Porcheddu, A.; Salaris, M. Simple one-flask method for the preparation of hydroxamic acids. Org. Lett. 2003, 5, 2715-2717.
https://doi.org/10.1021/ol034903j

[27]. Reddy, A. S.; Kumar, M. S.; Reddy, G. R. A convenient method for the preparation of hydroxamic acids. Tetrahedron Lett. 2000, 41, 6285-6288.
https://doi.org/10.1016/S0040-4039(00)01058-3

[28]. Rajic, Z.; Butula, I.; Zorc, B.; Kraljevic Pavelic, S.; Hock, K.; Pavelic, K.; Naesens, L.; De Clercq, E.; Balzarini, J.; Przyborowska, M.; Ossowski, T.; Mintas, M. Cytostatic and antiviral activity evaluations of hydroxamic derivatives of some non‐steroidal anti‐inflammatory drugs. Chem. Biol. Drug Des. 2009, 73, 328-338.
https://doi.org/10.1111/j.1747-0285.2009.00774.x

[29]. AbdelHafez, E.-S. M. N.; Aly, O. M.; Abuo-Rahma, G. E.-D. A. A.; King, S. B. Lossen rearrangements under Heck reaction conditions. Adv. Synth. Catal. 2014, 356, 3456-3464.
https://doi.org/10.1002/adsc.201400170

[30]. Brown, D. A.; Glass, W. K.; Mageswaran, R.; Girmay, B. cis-trans Isomerism in monoalkylhydroxamic acids by 1H, 13C and 15N NMR spectroscopy. Magn. Reson. Chem. 1988, 26, 970-973.
https://doi.org/10.1002/mrc.1260261107

[31]. Pirrung, M. C.; Chau, J. H.-L. A convenient procedure for the preparation of amino acid hydroxamates from esters. J. Org. Chem. 1995, 60, 8084-8085.
https://doi.org/10.1021/jo00129a059

[32]. Devlin, J. P.; Ollis, W. D.; Thorpe, J. E. Studies concerning the antibiotic actinonin. Part V. Synthesis of structural analogues of actinonin by the anhydride-ester method. J. Chem. Soc., Perkin Trans. 1 1975, 846-848.
https://doi.org/10.1039/P19750000846

[33]. Benguzzi, S.A.; El-warfalli, A.A. Synthesis and characterization of normal and N-substituted octanohydroxamic acid complexes. Der. Chem. Sin. 2014, 5, 47-50. https://www.imedpub.com/articles/synthesis-and-characterization-of-normal-and-nsubstitutedoctanohydroxamic-acid-complexes.pdf (accessed May 5, 2024).

[34]. Barbarić, M.; Uršić, S.; Pilepić, V.; Zorc, B.; Hergold-Brundić, A.; Nagl, A.; Grdiša, M.; Pavelić, K.; Snoeck, R.; Andrei, G.; Balzarini, J.; De Clercq, E.; Mintas, M. Synthesis, X-ray crystal structure study, and cytostatic and antiviral evaluation of the novel cycloalkyl-N-aryl-hydroxamic acids. J. Med. Chem. 2005, 48, 884-887.
https://doi.org/10.1021/jm040878r

[35]. Cerniauskaite, D.; Rousseau, J.; Sackus, A.; Rollin, P.; Tatibouët, A. Glucosinolate synthesis: A hydroxamic acid approach. European J. Org. Chem. 2011, 2011, 2293-2300.
https://doi.org/10.1002/ejoc.201001438

[36]. Fournand, D.; Pirat, J.-L.; Bigey, F.; Arnaud, A.; Galzy, P. Spectrophotometric assay of aliphatic monohydroxamic acids and α-, β-, and γ-aminohydroxamic acids in aqueous medium. Anal. Chim. Acta 1997, 353, 359-366.
https://doi.org/10.1016/S0003-2670(97)87798-7

[37]. Elliott, W. H. Adenosinetriphosphate in glutamine synthesis. Nature 1948, 161, 128-129.
https://doi.org/10.1038/161128a0

[38]. Johnston, R. B.; Mycek, M. J.; Fruton, J. S. Catalysis of transamidation reactions by proteolytic enzymes. J. Biol. Chem. 1950, 185, 629-641.
https://doi.org/10.1016/S0021-9258(18)56350-X

[39]. Grossowicz, N.; Wainfan, E.; Borek, E.; Waelsch, H. The enzymatic formation of hydroxamic acids from glutamine and asparagine. J. Biol. Chem. 1950, 187, 111-125.
https://doi.org/10.1016/S0021-9258(19)50936-X

[40]. Lowenstein, J. M. Non-enzymic formation of hydroxamates catalysed by manganous ions. Biochim. Biophys. Acta 1958, 28, 206-207.
https://doi.org/10.1016/0006-3002(58)90452-9

[41]. Chou, T. C.; Lipmann, F. Separation of acetyl transfer enzymes in pigeon liver extract. J. Biol. Chem. 1952, 196, 89-103.
https://doi.org/10.1016/S0021-9258(18)55708-2

[42]. Mathis, F. Acides hydroxamiques à fonction simple. Structure et propriétés générales. Ann. de la Fac. des Sciences de Toulouse 1961, 25, 125-146. http://www.numdam.org/item/AFST_1961_4_25__125_0/ (accessed May 5, 2024).
https://doi.org/10.5802/afst.498

[43]. Schouteden, F. On the conversion of amidoxime groups into hydroxamie acid groups in polyacrylamidoximes. Makromol. Chem. 1958, 27, 246-255.
https://doi.org/10.1002/macp.1958.020270121

[44]. Kumaran, G.; Kulkarni, G. H. Synthesis of α-functionalized and nonfunctionalized hydroximoyl chlorides from conjugated nitroalkenes and nitroalkanes. J. Org. Chem. 1997, 62, 1516-1520.
https://doi.org/10.1021/jo961553o

[45]. Cassel, S.; Casenave, B.; Déléris, G.; Latxague, L.; Rollin, P. Exploring an alternative approach to the synthesis of arylalkyl and indolylmethyl glucosinolates. Tetrahedron 1998, 54, 8515-8524.
https://doi.org/10.1016/S0040-4020(98)00465-7

[46]. Cerniauskaite, D.; Gallienne, E.; Karciauskaite, H.; Farinha, A. S. F.; Rousseau, J.; Armand, S.; Tatibouët, A.; Sackus, A.; Rollin, P. A simple O-sulfated thiohydroximate molecule to be the first micromolar range myrosinase inhibitor. Tetrahedron Letters 2009, 50, 3302-3305.
https://doi.org/10.1016/j.tetlet.2009.02.072

[47]. Porcheddu, A.; Giacomelli, G. Angeli−Rimini's reaction on solid support: A new approach to hydroxamic acids. J. Org. Chem. 2006, 71, 7057-7059.
https://doi.org/10.1021/jo061018g

[48]. Wang, Y.; Huang, W.; Xin, M.; Chen, P.; Gui, L.; Zhao, X.; Tang, F.; Wang, J.; Liu, F. Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors. Bioorg. Med. Chem. 2017, 25, 75-83.
https://doi.org/10.1016/j.bmc.2016.10.011

[49]. Floyd, C. D.; Lewis, C. N.; Patel, S. R.; Whittaker, M. A method for the synthesis of hydroxamic acids on solid phase. Tetrahedron Lett. 1996, 37, 8045-8048.
https://doi.org/10.1016/0040-4039(96)01821-7

[50]. Richter, L. S.; Desai, M. C. A TFA-cleavable linkage for solid-phase synthesis of hydroxamic acids. Tetrahedron Lett. 1997, 38, 321-322.
https://doi.org/10.1016/S0040-4039(96)02336-2

[51]. Mellor, S. L.; McGuire, C.; Chan, W. C. N-Fmoc-aminooxy-2-chlorotrityl polystyrene resin: A facile solid-phase methodology for the synthesis of hydroxamic acids. Tetrahedron Lett. 1997, 38, 3311-3314.
https://doi.org/10.1016/S0040-4039(97)00594-7

[52]. Bauer, U.; Ho, W.-B.; Koskinen, A. M. P. A novel linkage for the solid-phase synthesis of hydroxamic acids. Tetrahedron Lett. 1997, 38, 7233-7236.
https://doi.org/10.1016/S0040-4039(97)01678-X

[53]. Ngu, K.; Patel, D. V. A new and efficient solid phase synthesis of hydroxamic acids. J. Org. Chem. 1997, 62, 7088-7089.
https://doi.org/10.1021/jo971274g

[54]. Robinson, D. E.; Holladay, M. W. Convenient preparation of O-linked polymer-bound N-substituted hydroxylamines, intermediates for synthesis of N-substituted hydroxamic acids. Org. Lett. 2000, 2, 2777-2779.
https://doi.org/10.1021/ol006152g

[55]. Zhang, W.; Zhang, L.; Li, X.; Weigel, J. A.; Hall, S. E.; Mayer, J. P. Solid-phase synthesis of C-terminal peptide hydroxamic acids. J. Comb. Chem. 2001, 3, 151-153.
https://doi.org/10.1021/cc000067i

[56]. Adiguzel, E.; Yilmaz, F.; Emirik, M.; Ozil, M. Synthesis and characterization of two new hydroxamic acids derivatives and their metal complexes. An investigation on the keto/enol, E/Z and hydroxamate/hydroximate forms. J. Mol. Struct. 2017, 1127, 403-412.
https://doi.org/10.1016/j.molstruc.2016.07.081

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