Aminophosphonate

Aminophosphonates are organophosphorus compounds with the formula (RO)₂P(O)CH₂NR₂. These compounds are structural analogues of amino acids in which a carboxylic moiety is replaced by phosphonic acid or related groups.[1] Acting as antagonists of amino acids, they inhibit enzymes involved in amino acid metabolism and thus affect the physiological activity of the cell. These effects may be exerted as antibacterial, plant growth regulatory or neuromodulatory. They can act as ligands, and heavy metal complexes with aminophosphonates have medical applications.[2]

Phosphonates are more difficult to hydrolyse than phosphates.[3] Some aminophosphonates degrade to aminomethylphosphonic acid.[4]

Preparation

Aminophosphonates are often prepared by hydrophosphonylation, usually the condensation of imines and phosphorous acid. In the Pudovik reaction or Kabachnik–Fields reaction the esters of phosphorous acid are employed, e.g. diphenylphosphite. Because these compounds are of pharmaceutical interest, methods have been developed to induce these additions asymmetrically.[5][6]

Examples

• 
  Aminomethylphosphonic acid (AMPA), the simplest possible aminophosphonate.
• 
  Glyphosate, a common though contentious herbicide
• 
  ATMP is used in water treatment as antiscalant[7]
• 
  EDTMP, a chelating agent. Its ^153Sm complex (Quadramet) is used in the treatment of cancer
• 
  DTPMP

References

1. Pedro Merino; Eugenia Marqués-López; Raquel P. Herrera (2008). "Catalytic Enantioselective Hydrophosphonylation of Aldehydes and Imines". Advanced Synthesis & Catalysis. 350 (9): 1195–1208. doi:10.1002/adsc.200800131. hdl:10261/114023.
2. Tušek-Božić, LJ (2013). "Aminophosphonate metal complexes of biomedical potential". Current Medicinal Chemistry. 20 (16): 2096–117. doi:10.2174/0929867311320160004. PMID 23432587.
3. Orsini, F; Sello, G; Sisti, M (2010). "Aminophosphonic acids and derivatives. Synthesis and biological applications". Current Medicinal Chemistry. 17 (3): 264–89. doi:10.2174/092986710790149729. PMID 20214568.
4. Schwientek, M.; Rügner, H.; Haderlein, S.B.; Schulz, W.; Wimmer, B.; Engelbart, L.; Bieger, S.; Huhn, C. (2024). "Glyphosate contamination in European rivers not from herbicide application?" (PDF). Water Research. 263: 122140. doi:10.1016/j.watres.2024.122140.
5. Foroogh Bahrami; Farhad Panahi; Ali Khalafinezhad (2016). "Synthesis of new α-aminophosphonate derivatives incorporating benzimidazole, theophylline and adenine nucleobases using L-cysteine functionalized magnetic nanoparticles (LCMNP) as magnetic reusable catalyst: evaluation of their anticancer properties". RSC Advances. 6 (9): 5915–5924. Bibcode:2016RSCAd...6.5915B. doi:10.1039/C5RA21419J. hdl:10261/114023.
6. Mucha, Artur; Kafarski, Paweł; Berlicki, Łukasz (2011). "Remarkable Potential of the α-Aminophosphonate/Phosphinate Structural Motif in Medicinal Chemistry". Journal of Medicinal Chemistry. 54 (17): 5955–5980. doi:10.1021/jm200587f. PMID 21780776.
7. Tang, Yongming; Yang, Wenzhong; Yin, Xiaoshuang; Liu, Ying; Yin, Pengwei; Wang, Jintang (2008). "Investigation of CaCO3 scale inhibition by PAA, ATMP and PAPEMP". Desalination. 228 (1–3): 55–60. doi:10.1016/j.desal.2007.08.006.