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ORIGINAL ARTICLE
Year : 2011  |  Volume : 2  |  Issue : 2  |  Page : 78-86  

Design and one-pot synthesis of new α-aminophosphonates and antimicrobial activity


Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Date of Web Publication25-Nov-2011

Correspondence Address:
Soghra Khabnadideh
Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Science, Shiraz
Iran
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Source of Support: Financial assistance from the Shiraz University of Medical Sciences, Conflict of Interest: None


DOI: 10.4103/0976-9234.90219

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   Abstract 

Background: α-Aminophosphonates are bioisosters of amino acids and have several pharmacological effects. α-Aminophosphonates have been synthesized by various routes from reaction between an amine, an aldehyde, and phosphate compounds.
Materials and Methods: We synthesized 20 new α-aminophosphonates in the presence of FeCl3 in THF as a catalyst to facilitate the Manich-type reaction of aldehyde, amine and phosphite compounds to form the corresponding α-aminophosphonates in a one-pot, three-component reaction. In this study, the catalytic effect of ZnCl2 was also compared with FeCl3 in the synthesis of α-aminophosphonates. Results: The results showed that FeCl3 catalyzed the reaction in mild conditions to form α-aminophosphonates with high yields, but ZnCl2 did not give high yields of the compounds and the reaction took longer time in comparison to that taken by FeCl3 The chemical structures of all new compounds were confirmed by spectrophotometric methods (1HNMR, 13CNMR, IR). The compounds were investigated for antimicrobial activity against Escherichia coli, Bacillus subtilis, Salmonella typhi, Shigella sonnei, Proteus vulgaris, and Staphylococcus epidermidis. Conclusion: The new synthesized compounds did not show good antibacterial activity against the tested microorganisms

Keywords: α-Aminophosphonates, antibacterial activity, FeCl 3 , ZnCl 2


How to cite this article:
Rezaei Z, Khabnadideh S, Ghasemi Y, Fadaei M, Karimi Z. Design and one-pot synthesis of new α-aminophosphonates and antimicrobial activity. J Pharm Negative Results 2011;2:78-86

How to cite this URL:
Rezaei Z, Khabnadideh S, Ghasemi Y, Fadaei M, Karimi Z. Design and one-pot synthesis of new α-aminophosphonates and antimicrobial activity. J Pharm Negative Results [serial online] 2011 [cited 2019 Sep 23];2:78-86. Available from: http://www.pnrjournal.com/text.asp?2011/2/2/78/90219


   Introduction Top


The α-aminophosphonates are amino acid isosteres, which have found a wide range of applications in agricultural and medicinal chemistry. [1],[2],[3],[4],[5] It has been reported that some alkyl-substituted phosphonate compounds have antifungal activity, [7],[8] antibacterial activity, [9],[10],[11],[12] antitumor effects [13],[14],[15] and antiviral activity. [16] Also, the activities of α-aminophosphonates as peptidomimetics,[17] enzyme inhibitors, [18] haptens of catalytic antibodies, [19] herbicidals, [20] inhibitors of serine hydrolases [21] and inhibitors of UDP-galactopyranose mutase [22] are reported in literature.

A large number of methods for the preparation of diverse α-aminophosphonates have been published since the first synthesis by Fields. However, one-pot synthesis of α-aminophosphonates remains a favorite due to its versatile route and high-yielding reactions. Recently, three-component synthesis starting from aldehydes, amines and diethylphosphite or triethylphosphite has been reported by using metal chloride catalysts such as InCl 3 , [23] ZrCl 4 , AlCl 3 , [24] SbCl 3 /Al 2 O 3 , [25] and TaCl 5 -SiO 2 . [26] Many of these methods suffer from some drawbacks such as long reaction times, low yields of the products, requiring stoichiometric amounts of catalysts, costly and moisture sensitive catalysts and use of highly toxic or toxic catalysts.

Recently, we had reported one-pot three-component synthesis starting from aldehydes, amines and diethylphosphite using FeCl 3 as a catalyst for the formation of α-aminophosphonates.[27] As FeCl 3 suffers from being hygroscopic and is also a corrosive material, in this study the catalytic effect of ZnCl 2 was investigated for aminophosphonates preparation.

It has been reported that derivatives of aminophosphonates with thiazolyl sulfanilamide, aminobenzamide, aminohippuric acid, and aminophenyl acetic acid moieties have antibacterial effect. [9],[11] Here, we synthesized 20 new compounds of α-aminophosphonates with these moieties and all compounds were investigated as antibacterial agents.


   Materials and Methods Top


Chemistry

All solvents and reagents were purchased from Sigma or Merck Chemical Companies. The products were purified by column chromatography techniques. Nuclear Magnetic Resonance (NMR) spectra were recorded on a Brucker Avance DPX 500 MHz instrument.

In order to synthesize α-aminophosphonates, three components, benzaldehyde (5.0 mmol), aniline (5.0 mmol), and diethyl phosphate (5.5 mmol) were made to react in the presence of catalytic amount of FeCl3 or ZnCl2 [Scheme 1]. The reaction completely proceeded after 90 min with 73% yield in the presence of FeCl 3 , but it did not completely proceed even after 24 h using ZnCl 2 . The reactions were repeated with several aldehydes, amines and diethyl phosphate with similar molar ratios as above in the presence of catalytic amount of FeCl 3 or ZnCl 2 . The reactions proceeded between 120 and 210 min with excellent isolated yields (78-90%) in the presence of FeCl 3 , but they gave a very low yield after 24 h in the presence of ZnCl 2 . The results are summarized in [Table 1].
Table 1: Comparison of the effect of catalyst in preparation of α -aminophosphonates (compounds 1a, 1b, 3c, 1d, and 3f)


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General procedures for the synthesis of compounds

To a mixture of aldehyde (2 mmol), amine (1 mmol), and diethylphosphite (2.2 mmol) was added FeCl3 in Tetra Hydro Furan (THF) ( 0.1 mmol) and stirred at 60°C for the appropriate reaction time. After completion of the reaction, CH 2 Cl 2 (10 ml) was added and washed with H 2 O (10 ml). The organic phase was separated and dried over anhydrous Na 2 SO 4 . Solvent was evaporated in vacuo and the resulting crude product was purified by chromatography on a short column of silica gel (EtOAc/petroleum benzene , 1/3) and then recrystallized from petroleum benzene/dichloromethane (4/1) to give the pure α-aminophosphonates.

Tetraethyl [4,4′-solfunyl bis(1,4-phenylene) bis (azanedyl) bis(phenylmethyl)] diphosphonate (1a)

This compound formed after 120 min (90%; MP = 243°C). 1 H NMR (500 MHz, CDCl 3 ): 7.6 (d, 4H, J = 8.72 Hz, ArH), 7.32-7.45 (m, 10H, ArH), 6.57 (d, 4H, J = 8.72 Hz, ArH), 5.34 (s, 2H, NH) 4.74 (d, 1H, J CHPO = 24.07 Hz, CHP), 4.07-4.18 (m, 4H, OCH 2 CH 3 ), 3.89-3.95 (m, 4H, OCH 2 CH 3 ), 3.61-3.66 (m, 2H, OCH 2 CH 3 ), 3.72-3.77 (m, 2H, OCH 2 CH 3 ), 1.3 (t, 6H, J = 7.07 Hz, CH 3 ), 1.11 (t, 6H, J = 7.03 Hz, CH 3 ); 13 C NMR (125 MHz, CDCl 3 ): 135.27 (Ar-C), 131.58 (Ar-C), 129.49 (Ar-C), 129.23 (Ar-C), 128.76 (Ar-C), 128.11 (Ar-C), 113.46 (Ar-C), 64.08 (d, J = 6.86 Hz, OCH 2 CH 3 ), 66.68 (d, J = 7.17 Hz, OCH 2 CH 3 ), 56.42 (d, J = 149.48 Hz, CHP), 55.64 (OCH 3 ), 16.82 (d, J = 5.8 Hz, CH 3 ), 16.56 (d, J = 5.56 Hz, CH 3 ); FT-IR (KBr, cm−1 ): 3288.4 (N-H), 2985.6 (C-H), 1593.09 (Ar, C-C), 1519.8 (N-H), 1292.22 (SO 2 ), 1236.29 (P=O), 1047.27 (P-C-O).

Tetraethyl [4,4′-sulfonyl bis(1,4-phenylene) bis (azanedyl) bis((4-nitrophenyl)methylene) diphosphonate (2a)

This compound formed after 150 min (92%; MP = 231°C). 1 H-NMR (500 MHz, CDC1 3 ): 7.91 (d, j = 7.62 Hz ,4H, ArH), 7.42 (d, j = 6.96 Hz, 4H, ArH), 7.25 (d, j = 8.56 Hz, 4H, ArH), 6.40 (d, j = 6.31 Hz, 4H, ArH), 6.29-6.33 (m, 2H, NH), 4.71 (d, j = 12.65 Hz, 2H, CHP), 3.83-3.92 (m, 4H, OCH 2 CH 3 ), 3.72-3.79 (m, 2H, OCH 2 CH 3 ), 3.59-3.64 (m, 2H, OCH 2 CH 3 ), 1.01 (t, j = 7.05 Hz, 6H, CH 3 ), 0.92 (t, j = 7.07 Hz, 6H, CH 3 ); 13 C-NMR (125 MHz, CDC1 3 ): 150.30 (Ar-C), 147.76 (Ar-C), 147.73 (Ar-C), 143.80 (Ar-C), 131.00 (Ar-C), 129.12 (Ar-C), 129.12 (Ar-C), 129.06 (Ar-C), 123.83 (Ar-C), 113.18 (Ar-C), 63.93 (d, j = 7.01 Hz, OCH 2 CH 3 ), 63.55 (d, j = 7.07 Hz, OCH 2 CH 3 ), 54.04 (d, j = 149.65 Hz, CHP), 16.63 (d, j = 5.37 Hz, CH 3 ), 16.45 (d, j = 5.46 Hz, CH 3 ); FT-IR (KBr, cm−1 ): 32284.55 (N-H), 2983.67 (C-H), 1596.95 (Ar, C-C), 1517.87 (N-H), 1342.36 (NO 2 ), 1286.43 (SO 2 ), 1240.14 (P=O), 1051.13 (P-C-O).

Tetraethyl [4,4′-sulfonyl bis(1,4-phenylene ) bis (azanedyl) bis((3, 4, 5-trimethoxyphenyl)methylene) diphosphonate (3a)

This compound formed after 90 min (83%; MP = 241°C). 1H-NMR (500 MHz, DMSO): 8.31 (s, 2H, ArH), 7.48 (d, j0 = 8.32 Hz, 4H, ArH), 7.26 (s, 2H, NH), 6.91 (d, j = 8.39 Hz, 4H, ArH), 6.87 (s, 2H, ArH), 5.06 (d, j = 11.70 Hz, 2H, CHP), 4.01-4.02 (m, 4H, OCH 2 CH 3 ), 3.88-3.91 (m, 2H, OCH 2 CH 3 ), 3.74 (s, 12H, OCH 3 ) and 2H (OCH 2 CH 3 ), 3.62 (s, 6H, OCH 3 ), 1.14 (t, j = 6.22 Hz, 6H, OCH 2 CH 3 ), 1.05 (t, j = 6.8 Hz, 6H, OCH 2 CH 3 ); 13C-NMR (125 MHz, DMSO-d6): 153.43 (Ar-C), 151.99 (Ar-C), 151.89 (Ar-C), 137.78 (Ar-C), 132.54 (Ar-C), 130.19 (Ar-C), 129.08 (Ar-C), 113.58 (Ar-C), 106.73 (Ar-C), 63.36 (d, j = 6.87 Hz, OCH 2 CH 3 ), 63.27 (d, j = 6.82 Hz, OCH 2 CH 3 ), 60.81 (OCH 3 ), 56.76 (OCH 3 ), 54.31 (d, j = 152.41 Hz, CHP), 17.10 (d, j = 5.11 Hz, OCH 2 CH 3 ), 16.90 (d, j = 5.61 Hz, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ); 3278.76 (N-H), 2983.67 (C-H), 1593.09 (Ar, C-C), 1508.23 (N-H), 1328.86 (P=O), 1234.36 (C-O, OCH3), 1051.13 (PCO).

Bis [diethyl(N,N-dimethylphenyl) (phenylamino) methyl phosphonate] sulfoxide (4a)

This compound formed after 120 min with 77% yield (MP = 222°C). 1H-NMR (CDCl 3 , 500 MHz): 7.42 (d, j = 9.1 Hz, 8H, ArH), 6.86 (d, j = 9.1 Hz, 8H, ArH), 5.04 (d, j = 23.7 Hz, 2H, CHP ), 3.98-4.02 (m, 4H, OCH 2 CH 3 ), 3.85-3.90 (m, 2H, OCH 2 CH 3 ), 3.71 (S, 12H, CH 3 -N and 2H, OCH 2 CH 3 ), 1.13 (t, j = 6.9 Hz, 6H, CH 3 ), 1.04 (t, j = 6.9 Hz, 6H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 159.57 (Ar-C), 151.85 (Ar-C), 130.26 (Ar-C), 130.14 (Ar-C), 128.96 (Ar-C), 128.60 (Ar-C), 114.43 (Ar-C), 113.60 (Ar-C), 63.22 (d, jpcH2 = 6.9 Hz, OCH 2 CH 3 ), 55.86 (d, jpcH = 152.25 Hz, CHP), 54.14 (CH3-N), 17.11 (d, jpcH3 = 5.5 Hz, CH 3 ).

Bis [diethyl (4-hydroxy-3-methoxyphenyl)(phenylamino) methyl phosphonate] sulfoxide] (5a)

1 H-NMR (CDC1 3 , 500 MHz): 8.94 (S, 2H, NH 2 -CO), 7.61 (d, j = 8.6 Hz, 2H, ArH), 7.16 (S, 1H, ArH), 6.95 (d, j = 8 Hz, 1H, ArH), 6.83 (d, j = 8.6 Hz, 2H, ArH), 6.73 (d, j = 8 Hz, 1H, ArH), 5.75 (1H, NH-CHP), 5 (d, j = 23.5 Hz, 1H, CHP), 4.01-4.08 (m, 2H, OCH 2 CH 3 ), 3.87-3.92 (m, 1H, OCH 2 CH 3 ), 3.76 (S, 3H, OCH 3 ), 3.70-3.73 (m, 1H, OCH 2 CH 3 ), 1.18 (t, J = 7 Hz, 3H, CH 3 ), 1.7 (t, J = 7 Hz, 3H, CH 3 ); 13C-NMR (CDC1 3 , 125 MHz): 168.85 (CO), 150.95 (Ar-C), 148.13 (Ar-C), 146.90 (Ar-C), 129.57 (Ar-C), 127.94 (Ar-C), 123.02 (Ar-C), 121.89 (Ar-C), 115.87 (Ar-C), 113.55 (Ar-C), 113.15 (Ar-C), 63.18 (d, j = 7.8 Hz, OCH 2 CH 3 ), 56.54 (d, j = 149.2 Hz, CHP), 42.04 (CH 2 -NH), 17.12 (d, jpcH3 = 100 Hz, CHP).

Diethyl (phenyl) [4-(thiazole-2-yl) sulfamoyl-phenylamino] methyl phosphonate (1b)

This product formed after 180 min (85%, MP = 256°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.67 (d, j = 8.64 Hz, ArH), 7.34-7.47 (m, 5H, ArH), 7.01 (d, j = 4.51 Hz, 1H, ArH), 6.60 (d, j = 8.74 Hz, 2H, ArH), 6.44 (d, j = 4.09 Hz, 1H, ArH), 5.34 (s, 1H, CHPNH), 4.78 (d, j = 24.05 Hz, 1H, CHP), 4.10-4.19 (m, 2H, OCH 2 CH 3 ), 3.92-3.97 (m, 1H, OCH 2 CH 3 ), 3.63-3.70 (m, 1H, OCH 2 CH 3 ), 1.34 (t, j = 7.04 Hz, 3H, CH 3 ), 1.13 (t, j = 7.09 Hz, 3H, CH 3 ); 13 C-NMR (DMSO, 125 MHz): 169.03 (Ar-C), 51.28 (Ar-C), 151.18 (Ar-C), 137.12 (Ar-C), 130.43 (Ar-C), 129.16 (Ar-C), 128.95 (Ar-C), 128.43 (Ar-C), 128.09 (Ar-C), 125.58 (Ar-C), 113.17 (Ar-C), 108 (Ar-C), 63.40 (d, j = 6.11 Hz, OCH 2 CH3), 63.23 (d, j = 6.87 Hz, OCH 2 CH 3 ), 54.91 (d, j = 150.71 Hz, 1H, CHP), 17.14 (d, j = 4.7 Hz, OCH 2 CH 3 ), 16.89 (d, j = 4.7 Hz, OCH2CH 3 ); FT-IR (KBr, cm−1 ): 3282.62 (N-H), 2987.53 (C-H), 1591.16 (C-C, aromatic), 1296.08 (SO 2 ), 1230 (P=O), 1022.2 (P-C-O).

Diethyl (4-nitro-phenyl) [4-(thiazole-2-yl) sulfamoyl-phenylamino] methyl phosphonate (2b)

This product formed after 210 min (85%; MP = 243°C). 1 H-NMR (CDC1 3 , 500 MHz): 12.40 (s, 1H, SO 2 NH), 8.22 (d, j = 8. 25 Hz, 2H, ArH), 7.79 (d, j = 7.6 Hz, 2H, ArH), 7.45 (d, j = 41 Hz, 2H, ArH), 7.28-7.31 (m, 1H, CHPNH), 7.16 (d, j = 4.25 Hz, 1H, ArH), 6.88 (d, j = 8.45 Hz, 2H, ArH), 672 (d, j = 4.17 Hz, 1H, ArH), 5.44 (d, j = 12.70 Hz, 1H, CHP), 4.04-4.08 (m, 2H, OCH 2 CH 3 ), 3.94-3.98 (m, 1H, OCH 2 CH 3 ), 3.84-3.87 (m, 1H, OCH 2 CH 3 ), 1.17 (t, j = 6.92 Hz, 3H, OCH 2 CH 3 ), 1.09 (t, j = 6.92 Hz, 3H, OCH 2 CH 3 ); 13 C-NMR (DMSO, 125 MHz): 169.02 (Ar-C), 150.97 (Ar-C), 150.87 (Ar-C), 147.86 (Ar-C), 145.49 (Ar-C), 130.88 (Ar-C), 130.26 (Ar-C), 128.12 (Ar-C), 125.20 (Ar-C), 124.11 (Ar-C), 113.31 (Ar-C), 108.44 (Ar-C), 63.83 (d, j = 6.85 Hz, OCH 2 CH 3 ), 63.48 (d, j = 6.9 Hz, CH 3 ), 54.03 (d, j = 149.27 Hz, CHP), 17.10 (d, j = 5.07 Hz, OCH 2 CH 3 ), 16.92 (d, j = 5.37 Hz,OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3267.19 (N-H), 3026.10 (C-H), 1596.95 (C-C), 1346.22 (NO 2 ), 1290.29 (SO 2 ), 1236.29 (P=O), 1016.42 (P-C-O).

Diethyl [4-(thiazole-2-yl) sulfamoyl-phenylamino] (3, 4, 5-trimethoxy phenyl) methyl phosphonate (3b)

This product formed after 120 min (90%, MP = 181°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.96 (d, j = 8.86 Hz, 2H, ArH), 7.05 (d, j = 4.53 Hz, 1H, ArH), 6.69 (d, j = 1.96 Hz, 2H, ArH), 6.64 (d, j = 8.75 Hz, 2H, ArH), 6.45 (d, j = 4.49 Hz, 1H, ArH), 5.31(s, 1H, CHPNH), 4.70 (d, j = 23.75 Hz, 1H, CHP), 4.09 (m, 2H, OCH 2 CH 3 ), 3.97-4.02 (m, 1H, OCH 2 CH 3 ) 3.85 (d, 9H, OCH 3 ), 3.70-3.75 (m, 1H, OCH 2 CH 3 ), 1.31 (t, j = 7.06 Hz, 3H, OCH 2 CH 3 ), 1.17 (t, j = 7.05 Hz, 3H, OCH 2 CH 3 ); 13C-NMR (CDC1 3 , 125 MHz): 169.79 (Ar-C), 153.93 (Ar-C), 138.30 (Ar-C), 130.94 (Ar-C), 130.05 (Ar-C), 129.08 (Ar-C), 124.88 (Ar-C), 113.31 (Ar-C), 107.89 (Ar-C), 105.12 (Ar-C), 64.13 (d, j = 7.07 Hz, OCH 2 CH 3 ), 63.77 (d, j = 7.07 Hz, OCH 2 CH 3 ), 61.29 (OCH 3 ), 56.64 (OCH 3 ), 56.26 (d, j = 150.63 Hz, CHP), 16.87 (d, j = 5.05, OCH 2 CH 3 ), 16.69 (d, j = 5.62, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3286.48 (N-H), 2995.25 (C-H), 1593.09 (C-C, aromatic), 1326.93 (SO 2 ), 1244 (P=O), 1026.06 (P-C-O).

Diethyl (4-dimethyl aminophenyl) [4-(thiazole-2-yl) sulfamoyl-phenylamino] (phenyl amino) methyl phosphonate (4b)

This product formed after 150 min (87%; MP = 193°C). 1 H-NMR (CDC1 3 , 500 MHz): 12.41 (S, 1H, SO 2 NH), (d, j = 8.71 Hz, 2H, ArH), 7.31 (d, j = 7.29 Hz, 2H, ArH), 7.16 (d, j = 4.58 Hz, 1H, ArH), 6.98-7.01 (m, 1H, CHPNH), 6.83 (d, j = 8.75 Hz, 2H, ArH), 6.72 (d, j = 4.54 Hz, 1H, ArH), 6.65 (d, j = 8.58 Hz, 2H, ArH), 4.92 (d, j = 11.75 Hz, 1H, CHP), 3.97-4.05 (m, 2H, OCH 2 CH 3 ), 3.83-3.89 (m, 1H, OCH 2 CH 3 ), 3.68-3.73 (m, 1H, OCH 2 CH 3 ), 2.85 (s, 6H, NCH 3 ), 1.16 (t, j = 7.03 Hz, 3H, OCH 2 CH 3 ), 2.85 (s, 6H, NCH 3 ), 1.16 (t, j = 7.03 Hz, 3H, OCH 2 CH 3 ), 1.06 (t, j = 7.03 Hz, 3H, OCH 2 CH 3 ); 13 C-NMR (CDC1 3, 125 MHz): 151.50 (Ar-C), 151.39 (Ar-C), 150.68 (Ar-C), 129.99 (Ar-C), 129.82 (Ar-C), 128.01 (Ar-C), 123.75 (Ar-C), 113.18 (Ar-C), 112.75 (Ar-C), 108.37 (Ar-C), 63.10 (t, j = 7.6 Hz, OCH 2 CH 3 ), 53.72 (d, j = 153.57 Hz, CHP), 17.17 (d, j = 4.85 Hz, OCH 2 CH 3 ), 17.00 (d, j = 5.23, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3271.05 (N-H), 2902.67 (C-H), 1595.02 (C-C, aromatic), 1328.86 (C-N, NCH 3 ), 1294.15 (SO 2 ), 1232.43 (P=O), 1051.13 (P-C-O).

Diethyl (phenyl) (4-amidophenyl-amino) methyl phosphonate (1c)

This product formed after 120 min (84%, MP = 95°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.58 (d, J = 8.6 Hz, 2H, ArH), 7.53 (d. j = 8.6 Hz, 2H, ArH), 7.32 (t, j = 8.6 Hz, 2H, ArH), 7.24 (t, J = 8.6 Hz, 1H, ArH), 6.84 (m, 2H, NH 2 ), 6.8 (d, j = 8.6 Hz, 2H, ArH), 5.1 (d, J = 23.2 Hz, 1H, CHP), 4.02-4.06 (m, 2H, OCH 2 CH 3 ), 3.88-3.90 (m, 1H, OCH 2 CH 3 ), 3.72-3.74 (m, 1H, OCH 2 CH 3 ), 1.17 (t, J = 6 Hz, 3H, CH 3 ), 1.05 (t, J = 6.9 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 168.96 (CO), 150.76 (Ar-C), 150.65 (Ar-C), 137.31 (Ar-C), 129.58 (Ar-C), 129.12 (Ar-C), 128.86 (Ar-C), 128.34 (Ar-C), 123.06 (Ar-C), 113.12 (Ar-C), 63.32 (d, j = 6.6 Hz, OCH 2 CH 3 ), 56.93 (d, j =151.02 Hz, CHP), 17.02 (d, j =5.2 Hz, CH 3 ), 16.78 (d, j = 5.2 Hz, CH 3 ).

Diethyl (4-methoxy phenyl) (4-amidophenyl-amino) methyl phosphonate (2c)

This product formed after 120 min (87%, MP = 105°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.6 (d, j = 8.7 Hz, 2H, ArH), 7.46 (d, j = 6 Hz, 2H, ArH), 6.89 (d, j = 6 Hz, 2H, ArH), 6.84 (m, 2H, NH 2 ), 6.83 (d, j = 8.7 Hz, 2H, ArH), 5.75 (s, 1H, NH), 5.1 (d, j = 24.03, 1H, CHP), 4.03-4.07 (m, 2H, OCH 2 CH 3 ), 3.88 (m, 1H, OCH 2 CH 3 ), 3.74 (S, 3H, OCH 3 ), 3.70-3.72 (m, 1H, OCH 2 CH 3 ), 1.18 (t, j = 7 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 168.71 (CO), 159.53 (Ar-C), 150.84 (Ar-C), 130.34 (Ar-C), 129.54 (Ar-C), 129.14 (Ar-C), 123.1 (Ar-C), 114.34 (Ar-C), 113.17 (Ar-C), 63.2 (d. j = 6.3 Hz, OCH 2 CH 3 ), 55.86 (d, j = 152 Hz, CHP), 54.31 (OCH 3 ), 17.16 (d, j = 5.2 Hz, CH 3 ), 16.95 (d. j = 5.2 Hz, CH 3 ).

Diethyl (4-amidophenyl-amino) (4-hydroxy-3-methoxy phenyl) methyl phosphonate (3c)

This product formed after 120 min (81%, MP = 103°C). 1 H-NMR (CDC1 3 , 500 MHz): 8.94 (S, 2H, NH 2 -CO), 7.61 (d, j = 8.6 Hz, 2H, ArH), 7.16 (S, 1H, ArH), 6.95 (d, j = 8 Hz, 1H, ArH), 6.83 (d, j = 8.6 Hz, 2H, ArH), 6.73 (d, j = 8 Hz, 1H, ArH), 5.75 (1H, NH-CHP), 5 (d, J = 23.5 Hz, 1H, CHP), 4.01-4.08 (m, 2H, OCH 2 CH 3 ), 3.87-3.92 (m, 1H, OCH 2 CH 3 ), 3.76 (S, 3H, OCH 3 ), 3.70-3.73 (m, 1H, OCH 2 CH 3 ), 1.18 (t, J = 7 Hz, 3H, CH 3 ), 1.7 (t, J = 7 Hz, 3H, CH 3 ); 13 C-NMR (CDCl 3 , 125 MHz): 168.85 (CO), 150.95 (Ar-C), 148.13 (Ar-C), 146.90 (Ar-C), 129.57 (Ar-C), 127.94 (Ar-C), 123.02 (Ar-C), 121.89 (Ar-C), 115.87 (Ar-C), 113.55 (Ar-C) 113.15 (Ar-C), 63.18 (d, j = 7.8 Hz, OCH 2 CH 3 ), 56.54 (d, j = 149.2 Hz, CHP), 42.04 (CH 2 -NH), 17.12 (d, j = 100 Hz, CHP).

Diethyl (4-amidophenyl-amino) (4-hydroxy-3-methoxy phenyl) methyl phosphonate (4c)

This product formed after 150 min (72%, MP = 89°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.61 (d, j = 8.4 Hz, 2H, ArH), 7.2 (S, 1H, ArH), 7.07 (d, J = 8.4 Hz, 1H, ArH), 6.92 (S, 2H, NH 2 ), 6.9 (d, j = 8.4 Hz, 1H, ArH), 6.83 (d, j = 8.4 Hz, 2H, ArH), 5.06 (d, J = 23.3 Hz, 1H, CHP), 4.03-4.07 (m, 2H, OCH 2 CH 3 ), 3.90-3.92 (m, 1H, OCH 2 CH 3 ), 3.74 (S, 3H, OCH 3 ), 3.71 (S, 3H, OCH 3 ), 1.19 (t, J = 7.03 Hz, 3H, CH 3 ), 1.08 (t, J = 7.03 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 168.8 (CO), 163.18 (Ar-C), 150.98 (Ar-C), 150.78 (Ar-C), 149.22 (Ar-C). 149.1 (Ar-C), 129.58 (Ar-C), 123.1 (Ar-C), 121.52 (Ar-C), 113.19 (Ar-C), 112.18 (Ar-C), 63.2 (d, J = 6.8 Hz, OCH 2 CH 3 ), 56.34 (d, J = 152 Hz, CHP), 54.64 (OCH 3 ), 17.17 (d, J = 5.1 Hz, CH 3 ), 16.97 (d, J = 5.1 Hz, CH 3 ).

Diethyl (3, 4, 5-trimethoxy phenyl) (4-amidophenyl-amino) methyl phosphonate (5c)

This product formed after 180 min (78%; MP = 135°C). 1 H-NMR (CDC1 3 , 500 MHz): 7.6 (d, j = 8.8 Hz, 2H, ArH), 7.55 (S, 2H, NH 2 ), 6.91 (S, 2H, ArH), 6.84 (d, j = 8.8 Hz, 2H, ArH), 5.08 (d, j = 23.9 Hz, 1H, CHP), 4.04.08 (m, 2H, OCH 2 CH 3 ), 3.92-3.98 (m, 1H, OCH 2 CH 3 ), 3.78-3.80 (m, 1H, OCH 2 CH 3 ), 3.76 (S, 6H, OCH 3 ), 3.63 (S, 3H, OCH 3 ), 1. 19 (t, j = 7 Hz, 3H, CH 3 ), 1.08 (t, j = 7 Hz, 3H, CH 3 ); 13 C-NMR (CDCl 3 , 125 MHz): 168.71 (CO), 153.39 (Ar-C), 150.91 (Ar-C), 137.69 (Ar-C), 133.1 (Ar-C), 129.6 (Ar-C), 123.2 (Ar-C), 113.14 (Ar-C), 106.82 (Ar-C), 63.25 (d, j = 6.7 Hz, OCH 2 CH 3 ), 56.08 (d, j = 149.2 Hz, CHP), 55.06 (OCH 3 ), 17.19 (d, j = 5 Hz, CH 3 ), 16.96 (d, j = 5 Hz, CH 3 ).

Diethyl (phenyl)[4-(2-aminobenzoyl-acetic acid) amino] methyl phosphonate (1d)

This product formed after 180 min (80%, MP = 99°C). 1 H-NMR (CDC1 3 , 500 MHz): 8.49 (t, 1H, NHCHP), 7.55 (d, j = 7.4 Hz, 4H, ArH), 7.34 (t, j = 7.4 Hz, 2H, ArH), 7.26 (t, j = 7.4 Hz, 1H, ArH), 6.96 (m, 1H, NHCH 2 ), 6.86 (d, j = 7.4 Hz, 2H, ArH), 5.18 (d, j = 24.3 Hz, 1H, CHP), 4.03-4.07 (m, 2H, OCH 2 CH 3 ), 3.94 (S, 2H, CH 2 -NH) 3.88-3.93 (m, 1H, OCH 2 CH 3 ), 3.71-3.76 (m, 1H, OCH 2 CH 3 ), 1.18 (t, j = 7 Hz, 3H, CH 3 ), 1.06 (t, j = 7 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 171.59 (CO), 167.29 (CO), 150.99 (Ar-C), 151.1 (Ar-C), 137.4 (Ar-C), 129.32 (Ar-C), 129.18 (Ar-C), 128.88 (Ar-C), 128.36 (Ar-C), 113.22 (Ar-C), 63.28 (d. j = 6.6 Hz, OCH 2 CH 3 ), 54.95 (d, j = 150 Hz, CHP), 41.96 (CH 2 -NH), 17.15 (d, j = 4.9 Hz, CH 3 ), 16.90 (d, j = 4.9 Hz, CH 3 ).

Diethyl (3, 4, 5-trimethoxy phenyl) [4-(2-aminobenzoyl-acetic acid) amino] methyl phosphonate (2d)

This product formed after 120 min (77%, MP = 102°C). 1 H-NMR (CDC 13 , 500 MHz): 8.52 (t, 1H, NHCHP), 7.62 (d, j = 8.33 Hz, 2H, ArH), 6.94-66.96 (m, 1H, NHCH 2 ), 6.92 (S, 2H, ArH), 6.88 (d, j = 8.32 Hz, ArH), 5.11 (d, j = 3.7 Hz, 1H, CHP), 4.04-4.10 (m, 2H, OCH 2 CH 3 ), 3.9 3.96 (m, 2H, OCH 2 CH 3 ), 3.63 (S, 3H, OCH 3 ), 1.19 (t, j = 6.9 Hz, 3H, CH 3 ), 1.09 (t, j = 6.9 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 171.60 (CO), 167.31 (CO), 153.40 (Ar-C), 151.16 (Ar-C), 137.69 (Ar-C), 133 (Ar-C), 129.38 (Ar-C), 122.49 (Ar-C), 113.22 (Ar-C), 106.82 (Ar-C), 63.27 (d, j = 6.7 Hz, OCH 2 CH 3 ), 56.79 (d, j = 151, CHP), 55.03 (OCH 3 ), 41.95 (CH 2 -NH), 17.18 (d, j = 5.1 Hz, CH 3 ), 16.95 (d, j = 5.1 Hz, CH 3 ).

Diethyl (4-nitrophenyl) [4-(2-aminobenzoyl-acetic acid) amino] methyl phosphonate (3d)

This product formed after 120 min (82%, MP = 103°C). 1 H-NMR (CDC1 3 , 500 MHz): 8.49 (t, 1H, NH-CHP), 8.23 (d, j = 8.7 Hz, 2H, ArH), 7.82 (d, j = 8.7 Hz, 2H, ArH), 7.59 (d, j = 8.7 Hz, 2H, ArH), 7.10-7.13 (m, 1H, NH-CH 2 ), 6.87 (d, j = 8.7 Hz, 2H, ArH), 5.47 (d, j = 25.5 Hz, 1H, CHP), 4.05-4.12 (m, 2H, OCH 2 CH 3 ), 3.95-4 (m, 1H, OCH 2 CH 3 ), 3.90 (d, j = 5.9 Hz, 2H, CH 2 -NH), 3.85-3.88 (m, 1H, OCH 2 CH 3 ), 1.18 (t, j = 7.1 Hz, 3H, CH 3 ), 1.09 (t, j = 7.1 Hz, 3H, CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 171.05 (CO), 167.21 (CO), 150.65 (Ar-C), 147.78 (Ar-C), 145.84 (Ar-C), 130.31 (Ar-C), 129.37 (Ar-C), 124.04 (Ar-C), 123 (Ar-C), 113.31 (Ar-C), 63.62 (d, j = 6.7 Hz, OCH 2 CH 3 ), 54.66 (d, j = 149.2 Hz, CHP), 42.04 (CH 2 -NH), 17.12 (d. j = 5.4 Hz, CH 3 ), 16.94 (d, j = 5.4 Hz, CH 3 ).

Diethyl (4-ethanoeic acid phenylamino) (3,4-dimethoxyphenyl) methyl phosphonate (1f)

This product formed after 180 min (82%, MP = 152°C). 1 H-NMR (DMSO-d 6 , 500 MHz): 12.10 (S, 1H, COOH), 7.17 (s, 1H, ArH), 7.04 (d, j = 8.17 Hz, 1H, ArH), 6.91 (d, j = 8.27 Hz, 2H, ArH), 6.88 (d, j = 8.31 Hz, 1H, ArH), 6.75 (d, j = 8.32 Hz, 2H, ArH), 6.19-6.22 (m, 1H, NH), 4.92 (d, j = 12.15 Hz, 1H, CHP), 4.05-4.09 (m, 2H, OCH 2 CH 3 ), 3.86-3.92 (m. 1H, OCH 2 CH 3 ), 3.67-3.76 (m, 1H, OCH 2 CH 3 ), 3.74 (s, 3H, OCH 3 ), 3.71 (s, 3H, OCH 3 ), 3.33 (S, 2H, CH 2 COOH), 1.21 (t, j = 7.03 Hz, 3H, CH 2 CH 3 ), 1.08 (t, j = 7.25 Hz, 3H, OCH 2 CH 3 ); 13 C-NMR (DMSO-d 6, 125 MHz): 174.10 (COOH), 149.20 (Ar-C), 149.00 (Ar-C), 146.93 (Ar-C), 146.82 (Ar-C), 130.40 (Ar-C), 129.95 (Ar-C), 123.95 (Ar-C), 121.45 (Ar-C), 114.36 (Ar-C), 113.15 (Ar-C), 112.16 (Ar-C), 63.14 (d, j = 6.68 Hz, OCH 2 CH 3 ), 63.00 (d, j = 6.73 Hz, OCH 2 CH 3 ), 56.40 (OCH 3 ), 56.26 (OCH 3 ), 54.49 (d, j = 152.95 Hz, CHP), 40.37 (CH 2 COOH), 17.20 (d, j = 5.17 Hz, OCH 2 CH 3 ), 16.99 (d, j = 5.45 Hz, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3326.98 (N-H), 2987.53 (C-H), 1710.74 (C=O COOH), 1616.24 (C-C, aromatic), 1259.43 (P=O), 1236.29 (C-O, OCH 3 ), 1049.2 (P-C-O).

Diethyl (4-ethanoeic acid phenylamino) (3, 4, 5-trimethoxyphenyl) methyl phosphonate (2f)

This product formed after 150 min (80%, MP = 161°C). 1 H-NMR (CDC1 3 -500 MHz): 7.08 (d, j = 8.42 Hz, 2H, ArH), 6.69 (d, j = 2.17 Hz, 2H, ArH), 6.63 (d. j = 8.46 Hz, 2H, ArH), 4.69 (d, j = 24.40 Hz, 1H, CHP), 4.10-4.19 (m, 2H, OCH 2 CH 3 ), 3.93-39 (m, 1H, OCH 2 CH 3 ), 3.81 (s, 3H, OCH 3 ), 3.78 (s, 6H, OCH 3 ), 3.68-3.74 (m, 1H, OCH 2 CH 3 ), 3.51 (s , 2H, CH 2 COOH), 1.28 (t, j = 7.04 Hz, 3H, OCH 2 CH 3 ), 1.13 (t, j = 7.04 Hz, 3H, OCH 2 CH 3 ); 13 C-NMR (CDC1 3, 125 MHz): 176.38 (COOH), 153.72 (Ar-C), 146.06 (Ar-C), 145.94 (Ar-C), 137.99 (Ar-C), 131.71 (Ar-C), 130.43 (Ar-C), 124.11 (Ar-C), 114.38 (Ar-C), 105.27 (Ar-C), 64.20 (d, j = 6.95 Hz, OCH 2 CH 3 ), 64.06 (d, j = 7.11 Hz, OCH 2 CH 3 ), 61. 17 (OCH 3 ), 56.49 (d, j = 152.12 Hz, CHP), 56.44 (OCH 3 ), 40 83 (CH 2 COOH), 16.79 (d, j = 5.62 Hz, OCH 2 CH 3 ), 16.60 (d, j = 5.77 Hz, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3332.76 (N-H), 2987.53 (C-H), 1712.67 (C=O, COOH), 1591.16 (C-N, aromatic), 1326.93 (P=O), 1236.29 (C-O, OCH 3 ), 1054.99 (P-C-O).

Diethyl (4-ethanoeic acid phenylamino) (4-dimehtyl aminophenyl) methyl phosphonate (3f)

This product formed after 210 min (78%; MP = 157°C). 1 H-NMR (CDC 13 -500 MHz): 7.30 (d, j = 6.65 Hz, 2H, ArH), 7.06 (d, j = 8.40 Hz, 2H, ArH), 6.69 (d, j = 8.65 Hz, 2H, ArH), 6.61 (d, j = 8.43 Hz, 2H, ArH), 4.69 (d, j = 23.79 Hz, 1H, CHP), 4.09-4.18 (m, 2H, OCH 2 CH 3 ), 3.92-3.97 (m, 1H, OCH 2 CH 3 ), 3.66-3.71 (m, 1H, OCH 2 CH 3 ), 3.51 (s, 2H, CH 2 COOH), 2.93 (s, 6H,NCH 3 ), 1.29 (t, j = 7.1 Hz, 3H, OCH 2 CH 3 ), 1.15 (t, j = 7.06 Hz, 3H, OCH 2 CH 3 ); 13 C-NMR (CDC1 3 , 125 MHz): 176.69 (COOH), 150.62 (Ar-C), 146.18 (Ar-C), 146.05 (Ar-C), 130.38 (Ar-C), 129.06 (Ar-C), 123.68 (Ar-C), 123.31 (Ar-C), 114.44 (Ar-C), 113.13 (Ar-C), 63.90 (d, j = 4.5 Hz, OCH 2 CH 3 ), 63.85 (d, j = 4.35 Hz, OCH 2 CH 3 ), 55.62 (d, j = 153.45 Hz, CHP), 40.98 (NCH 3 ), 40.80 (CH 2 COOH), 16.83 (d, j = 5.67 Hz, OCH 2 CH 3 ), 16.67 (d, j = 5.81 Hz, OCH 2 CH 3 ); FT-IR (KBr, cm−1 ): 3380.98 (N-H), 2983 (C-H), 1726.17 (C=O, COOH), 1612.38 (C-C, aromatic), 1359.72 (C-N, NCH 3 ), 1236.29 (P=O), 1045.35 (P-C-O).

Antimicrobial assay

All the newly synthesized α-aminophosphonate compounds 1-20 were tested for their in vitro antibacterial activity against  Escherichia More Details coli (PTCC 1338), Bacillus subtilis (PTCC 1023),  Salmonella More Details typhi (PTCC 1609), Shigella sonnei (PTCC 1235), Proteus vulgaris (PTCC 1312), and Staphylococcus epidermidis (PTCC 1114). Minimum inhibitory concentration (MIC) values were determined by twofold serial dilution technique. For comparison of antimicrobial activity, ampicillin and gentamycin were used as the reference antibacterial agents.


   Results and Discussion Top


Chemistry

It has been reported that metal chlorides or metal halides are efficient catalysts for the preparation of aminophosphonate by three component reaction, [28] but ZnCl 2 is not an efficient catalyst for the formation of α-aminophosphonates. The recommended mechanism for the preparation of α-aminophosphonates using FeCl 3 as a catalyst is shown in scheme 1. In the presence of FeCl 3 , the reaction starts with activation of diethylphosphite, a tautomer form in which Phosphorus (V) changes to Phosphorus (III) with a free pair of electron. Then, the nitrogen of Schiff base which is formed in the first step of α-aminophosphonate formation donates a pair of electrons to make a coordinate bond with FeCl3 . This makes the nitrogen positively charged which induces partial positive charge on sp 2 carbon. The free pair of electrons of phosphorus attacks the partially positively charged carbon and a cyclic current of electron displacement protonates nitrogen and detaches the FeCl 3 to enter a new cycle. It seems that ZnCl 2 is not as efficient as FeCl 3 in this mechanism for formation of α-aminophosphonates. Therefore, new compounds 1-20 were prepared using FeCl3 as the catalyst. The reactions completely proceeded after 90-120 min in excellent isolated yields (76-92%) in the presence of FeCl 3 [Table 2]. The amines which were used for synthesis included dapsone (4,4′-diaminophenyl sulfone), thiazolyl sulfanilamide, aminobenzamide, aminohippuric acid, and aminophenyl acetic acid [Schemes 1-5]. It seems these amine moieties can affect the antibacterial activity.
Table 2: Synthesis of α -aminophosphonates using a three-component system with FeCl3 THF solution


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Antimicrobial assay

The new synthesized compounds did not show good antibacterial activity against the tested microorganisms. However, the antibacterial activity of α-aminophosphonates has been reported in the literature against gram-positive and gram-negative bacteria,[9],[10],[11],[12] but the new synthesized compounds in this paper had MIC more than 256 μg/ml against the investigated bacteria. It has been reported that pharmacological effects of α-aminophosphonates are sterospecific;[8] therefore, we suggest that antibacterial effect of these compounds may be stereoselective and the antibacterial evaluation of each enantiomer separately can confirm this matter.


   Conclusion Top


In conclusion, α-aminophosphonates are valuable compounds to be investigated as bioactive molecules and pharmacological agents. Recently, we have reported cytotoxic activity and one-pot three-component synthesis starting from aldehydes, amines and diethylphosphite using FeCl 3 as a catalyst for the formation of α-aminophosphonates.[27] In this study, synthesis of α-aminophosphonates using FeCl3 was compared with synthesis using ZnCl 2 . The results showed that ZnCl 2 was not an efficient catalyst for the synthesis of these α-aminophosphonates.


   Acknowledgment Top


Financial assistance from the Shiraz University of Medical Sciences is gratefully acknowledged.

 
   References Top

1.Engel R. Phosphonates as analogues of natural phosphates. Chem Rev 1977;77:349-67.  Back to cited text no. 1
    
2.Hiratake J, Oda J. "Aminophosphonic and aminoboronic acids as key elements of a transition state analogue inhibitor of enzymes". BiosciBiotechnolBiochem 1997;61:211-8.  Back to cited text no. 2
    
3.Schug KA, Lindner W. Noncovalent binding between guanidinium and anionic groups: Focus on biological-and synthetic-based arginine/guanidinium interactions with phosph [on] ate and sulf [on] ate residues. Chem Rev 2005;105:67-114.  Back to cited text no. 3
    
4.Moonen K, Laureyn I, Stevens CV. Synthetic methods for azaheterocyclicphosphonates and their biological activity. Chem Rev. 2004;104:6177-216.  Back to cited text no. 4
    
5.Palacios F, Alonso C, Santos JM. b-Phosphono-and phosphinopeptides derived from beta-amino-phosphonic and phosphinic acids. Curr Org Chem 2004;8:1481-96.  Back to cited text no. 5
    
6.Baylis EK, Campbell CD, Dingwall JG. 1-Aminoalkylphosphonous acids. Part 1. Isosteres of the protein amino acids. J Chem Soc Perkin 1198;4:2845-53.  Back to cited text no. 6
    
7.Ouimette D, Coffey M. Comparative antifungal activity of four phosphonate compounds against isolates of nine Phytophthora species. Phytopathology 1989;79:761-7.  Back to cited text no. 7
    
8.Yang S, Gao XW, Diao CL, Song BA, Jin LH, Xu GF, et al. Synthesis and antifungal activity of novel chiral aminophosphonates containing fluorine moiety. Chin J Chem 2006;24:1581-8.  Back to cited text no. 8
    
9.Kumara BS, Sankara AU, Reddy CS, Nayak S, Rajua CN. Synthesis, and antimicrobial activity of 2, 10-dichloro-6-substituted aminobenzyl-12H-dibenzo [d, g][1, 3, 2] dioxaphosphocin-6-oxides. ARKIVOC 2007;13:155-66.  Back to cited text no. 9
    
10.Sonar SS, Sadaphal SA, Labade VB, Shingate BB, Shingare MS. An efficient synthesis and antibacterial screening of novel oxazepineá-aminophosphonates by ultrasound approach. Phosphorus Sulfur Silicon Relat Elem 2010;185:65-73.  Back to cited text no. 10
    
11.Reddy MV, Kumar BS, Balakrishna A, Reddy C, Nayak S, Reddya C. One-pot synthesis of novel -amino phosphonates using tetramethylguanidine as a catalyst. ARKIVOC 2007;15:246-54.  Back to cited text no. 11
    
12.Balakrishna A, Suresh Reddy C, Naik S, Manjunath M, Naga Raju C. Synthesis, characterization and bio-activity of some new beta and alpha-aminophosphonates. Bull ChemSoc Ethiop 2009;23:69-75.  Back to cited text no. 12
    
13.Bloemink MJ, Diederen JJ, Dorenbos JP, Heetebrij RJ, Keppler BK, Reedijk J. Calcium ions do accelerate the DNA binding of new antitumor-active platinum aminophosphonate complexes. Eur J InorgChem 1999;1999:1655-7.  Back to cited text no. 13
    
14.Jin L, Song B, Zhang G, Xu R, Zhang S, Gao X, et al. Synthesis, X-ray crystallographic analysis, and antitumor activity of N-(benzothiazole-2-yl)-1-(fluorophenyl)-O, O-dialkyl-[alpha]-aminophosphonates. Bioorg Med ChemLett 2006;16:1537-43.  Back to cited text no. 14
    
15.Rao X, Song Z, He L. Synthesis and antitumor activity of novel aminophosphonates from diterpenicdehydroabietylamine. Heteroatom Chem 2008;19:512-6.  Back to cited text no. 15
    
16.Xu Y, Yan K, Song B, Xu G, Yang S, Xue W, et al. Synthesis and antiviral bioactivities of á-aminophosphonates containing alkoxyethyl moieties. Molecules 2006;11:666-76.  Back to cited text no. 16
    
17.Kafarski P, Lejczak B. Phosphorus Sulfur Silicon Relat Elem 1991;63:193-215.  Back to cited text no. 17
    
18.Allen MC, Fuhrer W, Tuck B, Wade R, Wood JM. Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond. J Med Chem 1989;32:1652-61.  Back to cited text no. 18
    
19.Smith AB, Taylor CM, Benkovik SJ, Stephen JB, Hirschman R. Peptide bond formation via catalytic antibodies: Synthesis of a novel phosphonatediesterhapten. Tetrahedron Lett 1994;35:6853-6.  Back to cited text no. 19
    
20.Hassal CH, Hahn EF. Antibiotics.Vol. 6. Berlin: Springer;1983.p. 1-11.  Back to cited text no. 20
    
21.Makhaeva G, Malygin V, Aksinenko AY, Sokolov V, Strakhova N, Rasdolsky A, et al., editors. Fluorinated -aminophosphonates-a new type of irreversible inhibitors of serine hydrolases. Berlin: Springer;2005.  Back to cited text no. 21
    
22.Pan W, Ansiaux C, Vincent SP. Synthesis of acyclic galactitol-and lyxitol-aminophosphonates as inhibitors of UDP-galactopyranosemutase. Tetrahedron Lett 2007;48:4353-6.  Back to cited text no. 22
    
23.Ranu BC, Hajra A, Jana U. General procedure for the synthesis of a-amino phosphonates from aldehydes and ketones using indium (III) chloride as a catalyst. Org Lett 1999;1:1141-3.  Back to cited text no. 23
    
24.Manjula A, Rao BV, Neelakantan P. One-pot synthesis of á-aminophosphonates: An inexpensive approach. Synth Commun 2003;33:2963-9.  Back to cited text no. 24
    
25.Ambica, Satish K, Subhash CT, Maninder SH, Kamal KK. One-pot synthesis of á-aminophosphonates catalyzed by antimony trichloride adsorbed on alumina.Tetrahedron Lett 2008;49:2208-12.   Back to cited text no. 25
    
26.Chandrasekhar S, Prakash SJ, Jagadeshwar V, Narsihmulu C. Three component coupling catalyzed by TaCl 5 -SiO 2: Synthesis of á-amino phosphonates. Tetrahedron Lett 2001;42:5561-3.  Back to cited text no. 26
    
27.Rezaei Z, Firouzabadi H, Iranpoor N, Ghaderi A, Jafari MR, Jafari AA, et al. Design and one-pot synthesis of á-aminophosphonates and bis (á-aminophosphonates) by iron (III) chloride and cytotoxic activity. Eur J Med Chem 2009;44:4266-75.  Back to cited text no. 27
    
28.Syamala M. Recent progress in three-component reactions. An update. Org Prep Proced Int 2009;41:1-68.  Back to cited text no. 28
    



 
 
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