α-(Imino)pyridyldifluoroethyl Phosphonates: Novel Promising Building Blocks in Synthesis of Biorelevant Aminophosphonic Acids Derivatives
Oksana Shavrina, Lyudmyla Bezgubenko, Andrii Bezdudny, Petro Onys’ko, Yuliya Rassukana
Organics · pp. 72–83 · Published 23 Apr 2021
10.3390/org2020007Abstract
A convenient synthetic approach to previously unknown NH-iminophosphonates bearing 2-, 3-, and 4-pyridyldifluoromethyl groups at the imine carbon atom was developed. The synthetic potential of these novel building blocks was demonstrated by their conversion into highly functionalized acyclic and heterocyclic aminophosphonates and phosphonic acids combining in their structure biorelevant aminophosphonic fragment, difluoromethyl group, and pyridyl, piperidyl, thiazolidin-4-one, or thiazidinan-4-one heterocyclic moieties in a single molecular platform.
References (24)
- 1 Kukhar, V.P., and Hudson, H.R. (2000). Aminophosphonic and Aminophosphinic Acids. Chemistry and Biological Activity, John Wiley & Sons.
- 2 Kafarski, 1991, Biological activity of aminophosphonic acids [DOI]
- 3 Mucha, 2011, Remarkable potential of the α-aminophosphonate/phosphinate structural motif in medicinal chemistry [DOI]
- 4 Orsini, 2010, Aminophosphonic acids and derivatives. Synthesis and biological applications [DOI]
- 5 Marrs, E.C.L., Varadi, L., Bedernjak, A.F., Day, K.M., Gray, M., Jones, A.L., Cummings, S.P., Anderson, R.J., and Perry, J.D. (2020). Phosphonopeptides revisited, in an era of increasing antimicrobial resistance. Molecules, 25. [DOI]
- 6 Smart, 2001, Fluorine substituent effects (on bioactivity) [DOI]
- 7 Purser, 2008, Fluorine in medicinal chemistry [DOI]
- 8 Wanat, 2020, New crystal structures of fluorinated α-aminophosphonic acid analogues of phenylglycine [DOI]
- 9 Cytlak, 2017, Latest achievements in the preparation of fluorinated aminophosphonates and aminophosphonic acids [DOI]
- 10 Burgey, 2003, Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines [DOI]
- 11 Qian, 2018, Design, synthesis, and structure-activity relationship studies of novel tetrazole antifungal agents with potent activity, broad antifungal spectrum and high selectivity [DOI]
- 12 Vitaku, 2014, Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA Approved Pharmaceuticals [DOI]
- 13 Nifant’ev, E.Y. (1983). Chemistry of Hydrophosphoryl Compounds, Nauka. (In Russian).
- 14 Orlovskii, 1976, Interaction of dialkyl phosphites with nitriles
- 15 Midrier, 2011, Hydrophosphonylation of alkenes or nitriles by double radical transfer mediated by titanocene/propylene oxide [DOI]
- 16 Zimin, 1978, Reaction of sodium salts of dialkylphosphorous acids with carboxylic acid nitriles [DOI]
- 17 Rassukana, 2007, α-Iminotrifluoroethylphosphonates: The first representatives of NH imidoyl phosphonates
- 18 Rassukana, 2014, Fluorinated NH-iminophosphonates and iminocarboxylates: Novel synthons for the preparation of biorelevant α-aminophosphonates and carboxylates [DOI]
- 19 Rassukana, 2014, Chemoselectivity of reactions of haloacetonitriles with hydrogen phosphonates: Dramatic effect of the nature of halogen atom [DOI]
- 20 Blanch, J.J. (1966). Determination of the Hammett substituent constants for the 2-, 3-, and 4-pyridyl and -pyridinium groups. J. Chem. Soc. B, 937–939. [DOI]
- 21 Khomutnik, 2013, N-aryltrifluoroacetimidoylphosphonates [DOI]
- 22 Chudakova, 2020, α-Ketophosphonates in the synthesis of α-iminophosphonates [DOI]
- 23 Hansch, 1991, A survey of Hammett substituent constants and resonance and field parameters [DOI]
- 24 Rassukana, 2009, A new strategy for asymmetric synthesis of aminophosphonic acid derivatives: The first enantioselective catalytic reduction of C-phosphorylated N-H imines [DOI]
Cited by 6
Oksana M. Shavrina, P. P. ONYS'KO, Yuliya V. Rassukana · Journal of Fluorine Chemistry · 2022
Oksana M. Shavrina, Yuliya V. Rassukana, P. P. ONYS'KO · Current Organic Synthesis · 2023
P. P. ONYS'KO, Yuliya V. Rassukana · Elsevier eBooks · 2025
T. Olszewski · Organics · 2024
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