dpl-2011-3-4-134-142

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Der Pharmacia Lettre, 2011: 3 (4)134-142

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ISSN 0974-248X USA CODEN: DPLEB4

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Microwave synthesis and anti-microbial activity of dibutyl (substituted)(4-(N-pyrimidin-2-yl-sulfamoyl)phenylamino) methylphosphonates

Chinta Raveendra Reddy, Chinthaparthi Radha Rani, Gangireddy Chandra Sekhar Reddy

and Chamarthi Naga Raju*

Department of Chemistry, Sri Venkateswara University, Tirupati ______________________________________________________________________________

ABSTRACTS A simple, efficient and green method has been developed for the synthesis of α-aminophosphonic acid esters in solvent-free under microwave irradiation with high yields. The newly synthesized compounds were characterized by IR, NMR (1H, 13C and 31P), Mass and C, H, N analysis. They exhibited moderate to high anti-microbial activity. Keywords: α-Aminophosphonates, Microwave irradiation, Pudovik reaction, sulphadiazine, anti-microbial activity. ______________________________________________________________________________

INTRODUCTION Phosphorus-carbon bond formation has attracted much attention because of its application in organic synthesis and bioorganic chemistry. The synthesis and use of phosphonate-containing molecules those possess C-P bonds are an important class of active compounds, have received great attention during the last two decades [1].

In this phosphonate chemistry, α-functionalized phosphonic acid esters are valuable intermediates for the preparation of medicinal compounds and synthetic intermediates [2-5]. Among α-functionalized phosphonic acid esters, α-aminophosphonic acid esters are an important class of compounds that exhibit a variety of interesting and useful properties in modern pharmaceutical chemistry [6]. As structural analogues of amino acids [2], their biological activity is mainly displayed through metabolic regulation and ability to inhibit various metalloenzymes having an amino acid as substrate [3]. In addition, a number of these compounds act as antibiotic [4], antimicrobial [5a-c], antioxidant [5b], antitumor [7a,7b] and antiviral agents [8a,8b]. In agrochemistry some derivatives are used as fungicidal [9] and herbicidal agents [10]. Another aspect regarding this kind of compounds arises from their ability of forming various types of metal complexes, which are also interesting because of their biological activity [11]. Thus, some complexes of platinum

Chamarthi Naga Raju et al Der Pharmacia Lettre 2011: 3 (4)134-142 _____________________________________________________________________________


group metals have shown remarkable antitumor activity [12,13]. The high phosphonate affinity to bone and other calcified tissues may be utilized for the drug design against bone diseases [14]. A number of synthetic methods for the construction of α-aminophosphonates have been reported [15] but the nucleophilic addition reaction of phosphites to imines is the most powerful and attractive method. In this context, some catalysts and procedures have been reported [16-19]. Of these, the Pudovik reaction is the most convenient method for the formation of C-P bond. The key step in the Pudovik reaction is the addition of dialkylphosphite to Schiff’s bases in generation of α-hydroxy/ α-aminophosphonates. In this connection, we herein report solvent-free synthesis of α-aminophosphonates under microwave irradiation with high yields.

MATERIALS AND METHODS

OMe

OEt

Compd. R MWI (min) Yield

5a

OEt

OMe

OMe

OMe

OH

OHHO

Cl

Cl

N

NH

N

NO2

5b

5c

5j

5i

5h

5g

5f

5e

5d

Compd. R MWI (min) Yield

4+5

4+5

4+5

5+6

3+5

5+5

3+6

3+6

4+6

3+5

88

82

86

83

85

78

80

81

84

75

Scheme-1: Synthesis of dibutyl (substituted)(4-(N-pyrimidin-2-ylsulfamoyl) phenylamino)methyl

phosphonates (5a-j)



All the chemicals are procured from Sigma-Aldrich, Merck and Lancaster were used as such without further purification. All solvents used for spectroscopic and other physical studies were reagent grade and were further purified employing the reported methods. The melting points were determined in open capillary tubes on a Guna Digital Melting Point apparatus and are uncorrected. IR spectra (νmax in cm-1) were recorded as KBr pellets using Perkin-Elmer spectrophotometer at APL Research centre, Hyderabad. The 1H-, 13C- and 31P-NMR Spectra were recorded on Bruker AMX 300 MHz NMR Spectrometer operatining at 300 MHz for 1H-, 75.4 MHz for 13C- and 161.9 MHz for 31P-NMR. All compounds were dissolved in DMSO-d6 and chemical shifts were referenced to TMS (1H- and 13C-NMR) and 85% H3PO4 (

31P-NMR) and Mass spectra were recorded on API 2000 Perkin-Elmer PE-SCIEX Mass spectrometer. Micro-analytical data were obtained from University of Hyderabad, Hyderabad, India.

RESULTS AND DISCUSSION

A series of novel α-aminophosphonates (5a-j) were conveniently synthesized by equimolar quantities of various aldimines (3a-j) which were previously prepared from various aldehydes (2a-j) and sulphadiazine (1) under microwave irradiation (MWI) in 3-5 min in ethanol and dibutyl hydrogen phosphite (4) in solvent-free and catalyst-free conditions under MWI. The reaction proceeded smoothly and completed in 3-10 min to afford the corresponding α-aminophosphonates in high yields (75-88%). The chemical structures of all the title compounds were confirmed by elemental analysis, IR, 1H-, 13C- and 31P- NMR spectra. All the newly synthesised α-aminophosphonates (5a-j) were tested for their anti-microbial activity. They possess moderate to high activity towards both bacteria and fungi. The IR spectra of the title compounds (5a-j) showed absorption bands at 3352-3369 cm-1 (N-H), 1432-1442 cm-1 (C-N), 1222-1232 cm-1 (P=O) and 1060-1069 cm-1 (S=O). All the aromatic protons of the title compounds (5a-j) gave complex multiplets in the region of δ 6.84-8.75. P-CH-N protons appeared as a doublet of doublet in the region of δ 5.04-5.45, due to its coupling with phosphorus and neighbouring N-H protons. The N-H proton gave a broad singlet peak in the range of δ 10.65-11.86. All the remaining protons resonated at their corresponding resonance region. The 13C-NMR spectra of 5a, 5b, 5e, 5g, 5h and 5j were recorded and all the carbon chemical shifts for the titled compounds were resonated in their appropriate regions and presented in experimental section. In the mass spectra, compounds exhibited their molecular ion peaks at their corresponding m/z values. The 31P-NMR signals appeared as singlets in the region 18.65-23.61 ppm in all the title compounds. General Procedure for the Synthesis of dibutyl (Substituted)(4-(N-pyrimidin-2-ylsulfamoyl)phenylamino) methylphosphonate (5a-j): In the first step, the solution of sulphadiazine (1, 0.005 mol) and various aldehydes (2a-j, 0.005 mol) in ethanol were irradiated by microwaves at 210 W for 3-5 min. After completion of the reaction (TLC) the mixture was cooled to rt, filtered and washed with cold ethanol to afford corresponding 4-(substituted imino)-N-(pyrimidin-2-yl)benzenesulfonamide (3a-j) in 80-85% yield. In the second step imines (3a-j, 0.005 mol) and dibutylphosphite (4, 0.005 mol) were sufficiently mixed and exposed to microwave irradiation (MWI) in the CATA-4R - Scientific Microwave Oven (Catalyst Systems) at 230 W in ambient pressure. The reaction mixtures were heated successively twice for 2-3 min period each time followed by a 1 min cooling interval between irradiations. This method was designed to avoid continuous overheating of reactants.31 The reaction mixtures were kept under stirring to maintain the homogeneity of the irradiating field



throughout the reaction. By monitoring with TLC, the reaction was stopped after 3-6 min. The obtained crude products were recrystallized from ethyl acetate to afford pure 5a-j as solids with 75-88% yield. All the newly synthesized compounds were characterized by IR, 1H-, 13C-, 31P- NMR, mass spectral and C, H, N analytical data. Physical, analytical and spectral data for the compounds (5a-j) Dibutyl (4-ethoxy-3-methoxyphenyl)(4-(N-pyrimidin-2-ylsulfamoyl)phenylamino) methylphospho -nate (5a): IR(KBr) cm-1: 3369 (N-H), 2960 & 2935 (C-Haromatic), 2873 (C-Haliphatic), 1441(C-N), 1230 (P=O), 1064 (S=O), 1034 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.75 (2H, bs, 2 × NH), 6.86-8.49 (10H, m, Ar-H), 5.05-5.20 (1H, dd, J = 23 Hz and J = 11 Hz, P-CH-N), 3.99 (2H, q, J = 6.0 Hz, Ar-OCH2), 3.94 (4H, m, P-OCH2), 3.73 (3H, s, Ar-OCH3), 1.36 (3H, t, J = 5.6 Hz, -CH3), 1.31 (4H, m, 2 × CH2), 1.26 (4H, m, 2 × CH2), 0.78 (6H, m, 2 × CH3);

13C-NMR (δ ppm): 60.2 (C-2), 152.2 (C-4), 108.7 (C-5a&5b), 132.1 (C-6a&6b), 129.5 (C-7), 170.7 (C-10), 160.6 (C-12a&12b), 113.9 (C-13), 127.8 (C-3� ), 109.7 (C-4� ), 151.3 (C-5�), 149.8 (C-6� ), 113.2 ((C-7� ), 120.2

(C-8�), 55.8 (C-9�), 66.2 (C-10� ), 15.7 (C-11� ), 67.8 (2 × C-3�� ), 30.5 (C-4� � ), 16.8

(C-5 � � ), 12.5 (C-6 � � ); 31P-NMR (δ, ppm): 18.65; MS: (m/z) 607 (M+1, 25), 606 (M+•), 357 (100), 278 (5). Anal.Calcd for C28H39N4O7PS: C, 55.43; H, 6.48; N, 9.24. Found: C, 55.36; H, 6.43; N, 9.19. Dibutyl (3,4-dimethoxyphenyl)(4-(N-pyrimidin-2-ylsulfamoyl)phenylamino) methylphosphonate (5b) IR(KBr) cm-1: 3360 (N-H), 2962 & 2939 (C-Haromatic), 2875 (C-Haliphatic), 1435(C-N), 1223 (P=O), 1061 (S=O), 1032 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.15 (2H, bs, 2 × NH), 6.89-8.50 (10H, m, Ar-H), 5.10-5.23 (1H, dd, J = 24 Hz and J = 12 Hz, P-CH-N), 3.96 (4H, m, 2 × -OCH2), 3.70 (3H, s, 2 × -OCH3), 1.30 (4H, m, 2 × CH2), 1.21 (4H, m, 2 × CH2), 0.81 (6H, m, 2 × CH3);

13C-NMR (δ ppm): 60.7 (C-2), 152.5 (C-4), 108.4 (C-5a&5b), 132.5 (C-6a&6b), 130.1 (C-7), 170.2 (C-10), 161.3 (C-12a&12b), 113.5 (C-13), 128.5 (C-3� ), 110.2 (C-4� ), 150.8 (C-5�), 149.9 (C-6� ), 113.6 ((C-7� ), 120.8 (C-8�), 56.4 (C-9�), 66.8 (C-10� ), 15.9 (C-11� ), 68.5 (2 × C-3�� ), 30.1 (C-4� � ), 15.5 (C-5 � � ), 12.9 (C-6 � � ); 31P-NMR (δ, ppm): 20.76; MS: (m/z) 593 (M+1, 12), 592 (M+•, 10). Anal.Calcd for C27H37N4O7PS: C, 54.72; H, 6.29; N, 9.45. Found: C, 54.64; H, 6.23; N, 9.40. Dibutyl (3-ethoxy-4-methoxyphenyl)(4-(N-pyrimidin-2-ylsulfamoyl)phenylamino) methylphospho -nate (5c) IR(KBr) cm-1: 3368 (N-H), 2961 & 2937 (C-Haromatic), 2875 (C-Haliphatic), 1440(C-N), 1232 (P=O), 1063 (S=O), 1031 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.70 (2H, bs, 2 × NH), 6.84-8.45 (10H, m, Ar-H), 5.04-5.20 (1H, dd, J = 23 Hz and J = 11 Hz, P-CH-N), 4.01 (2H, q, J = 6.0 Hz, Ar-OCH2), 3.95 (4H, m, P-OCH2), 3.71 (3H, s, Ar-OCH3), 1.32 (3H, t, J = 5.6 Hz, -CH3), 1.30 (4H, m, 2 × CH2), 1.25 (4H, m, 2 × CH2), 0.73 (6H, m, 2 × CH3);

31P-NMR (δ, ppm): 18.92; Anal.Calcd for C28H39N4O7PS: C, 55.43; H, 6.48; N, 9.24. Found: C, 55.35; H, 6.44; N, 9.19. Dibutyl (3,5-di-tert-butyl-2-hydroxyphenyl)(4-(N-py rimidin-2-ylsulfamoyl) phenylamino)methyl -phosphonate (5d) IR(KBr) cm-1: 3446 (O-H), 3365 (N-H), 2963 & 2936 (C-Haromatic), 2875 (C-Haliphatic), 1438(C-N), 1228 (P=O), 1061 (S=O), 1038 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 10.65 (2H, bs, 2 × NH), 6.91-8.53 (9H, m, Ar-H), 5.09-5.45 (1H, dd, J = 22 Hz and J = 10d Hz, P-CH-N), 5.21 (1H, bs, OH), 3.87 (4H, m, P-OCH2), 1.33 (4H, m, 2 × CH2), 1.25 (4H, m, 2 × CH2), 1.21 (9H, s, 3 × -



CH3), 0.72 (6H, m, 2 × CH3); 31P-NMR (δ, ppm): 19.50; MS: (m/z) 660 (M+•). Anal.Calcd for

C33H49N4O6PS: C, 59.98; H, 7.47; N, 8.48. Found: C, 59.92; H, 7.42; N, 8.40.

Dibutyl (3,5-dihydroxyphenyl)(4-(N-pyrimidin-2-ylsu lfamoyl)phenylamino) methylphosphonate (5e) IR(KBr) cm-1: 3452 (O-H), 3358 (N-H), 2958 & 2932 (C-Haromatic), 2878 (C-Haliphatic), 1438 (C-N), 1226 (P=O), 1060 (S=O), 1037 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.01 (2H, bs, 2 × NH), 6.85-8.51 (10H, m, Ar-H), 5.10-5.35 (1H, dd, J = 24 Hz and J = 12 Hz, P-CH-N), 5.70 (2H, bs, 2 × -OH), 3.91 (4H, m, 2 × -OCH2), 1.36 (4H, m, 2 × -CH2), 1.23 (4H, m, 2 × -CH2), 0.75 (6H, m, 2 × CH3);

13C-NMR (δ ppm): 60.2 (C-2), 151.8 (C-4), 108.8 (C-5a&5b), 132.1 (C-6a&6b), 129.5 (C-7), 171.3 (C-10), 160.5 (C-12a&12b), 113.8 (C-13), 132.4 (C-3� ), 107.4 (C-4� & 8� ), 156.5 (C-5� &7� ), 105.6 (C-6� ), 68.1 (2 × C-3�� ), 30.7 (C-4� � ), 15.8 (C-5 � � ), 12.7 (C-6 � � ); 31P-NMR (δ, ppm): 22.63; MS: (m/z) 564 (M+1, 20), 592 (M+•). Anal.Calcd for C25H33N4O7PS: C, 53.18; H, 5.89; N, 9.92. Found: C, 53.10; H, 5.83; N, 9.85. Dibutyl (2,4-dichlorophenyl)(4-(N-pyrimidin-2-ylsul famoyl)phenylamino) methylphosphonate(5f) IR(KBr) cm-1: 3352 (N-H), 2951 & 2928 (C-Haromatic), 2877 (C-Haliphatic), 1432 (C-N), 1229 (P=O), 1063 (S=O), 1034 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.21 (2H, bs, 2 × NH), 6.87-8.65 (10H, m, Ar-H), 5.11-5.33 (1H, dd, J = 20 Hz and J = 11 Hz, P-CH-N), 3.97 (4H, m, 2 × -OCH2), 1.38 (4H, m, 2 × -CH2), 1.22 (4H, m, 2 × -CH2), 0.71 (6H, m, 2 × CH3);

31P-NMR (δ, ppm): 23.31; MS: (m/z) 600 (M+•). Anal.Calcd for C25H31Cl2N4O5PS: C, 49.92; H, 5.19; N, 9.31. Found: C, 49.85; H, 5.12; N, 9.26. Dibutyl (4-(pyridin-2-yl)phenyl)(4-(N-pyrimidin-2-y lsulfamoyl)phenylamino) methylphosphonate (5g) IR(KBr) cm-1: 3365 (N-H), 2960 & 2935 (C-Haromatic), 2878 (C-Haliphatic), 1438 (C-N), 1222 (P=O), 1069 (S=O), 1029 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 10.66 (2H, bs, 2 × NH), 7.12-8.75 (15H, m, Ar-H), 5.12-5.31 (1H, dd, J = 24 Hz and J = 12 Hz, P-CH-N), 3.89 (4H, m, 2 × -OCH2), 1.32 (4H, m, 2 × CH2), 1.20 (4H, m, 2 × CH2), 0.76 (6H, m, 2 × CH3);

13C-NMR (δ ppm): 64.6 (C-2), 151.5 (C-4), 109.4 (C-5a&5b), 132.1 (C-6a&6b), 129.8 (C-7), 170.9 (C-10), 160.3 (C-12a&12b), 114.5 (C-13), 132.5 (C-3� ), 122.2 (C-4� & 8� ), 127.3 (C-5� &7� ), 140.4 (C-6� ), 156.3 (C-9� ), 148.8 (C-11� ), 120.4 (C-12� ), 138.8 (C-13� ), 118.9 (C-14� ), 68.1 (2 ×

C-3�� ), 30.9 (C-4� � ), 16.5 (C-5 � � ), 13.5 (C-6 � � ); 31P-NMR (δ, ppm): 23.61; MS: (m/z) 609 (M+•). Anal.Calcd for C30H36N5O5PS: C, 59.10; H, 5.95; N, 11.49. Found: C, 59.03; H, 5.90; N, 11.43. Dibutyl (1H-indol-3-yl)(4-(N-pyrimidin-2-ylsulfamoy l)phenylamino)methylphosphonate (5h) IR(KBr) cm-1: 3360 (N-H), 2958 & 2932 (C-Haromatic), 2875 (C-Haliphatic), 1439 (C-N), 1225 (P=O), 1062 (S=O), 1031 (P-O-Caliphatic);


13C-NMR (δ ppm): 65.8 (C-2), 151.2 (C-4), 110.1 (C-5a&5b), 131.6 (C-6a&6b), 129.2 (C-7), 170.4 (C-10), 159.6 (C-12a&12b), 114.8 (C-13), 113.3 (C-3� ), 122.7 (C-4� ), 139.4 (C-6� ), 113.3 (C-7� ), 124.1 (C-8� ), 120.9 (C-9� ), 119.8 (C-10� ), 128.5 (C-11� ), 68.4 (2 × C-3�� ), 32.4 (C-4� � ), 17.2 (C-5 � � ), 13.8 (C-6 � � ); 31P-NMR (δ, ppm): 21.52; MS: (m/z) 571 (M+•). Anal.Calcd for C27H34N5O5PS: C, 56.73; H, 6.00; N, 12.25. Found: C, 56.65; H, 5.94; N, 12.18.



Dibutyl (4-(dimethylamino)phenyl)(4-(N-pyrimidin-2- ylsulfamoyl)phenylamino) methylphospho -nate (5i) IR(KBr) cm-1: 3358 (N-H), 2952 & 2935 (C-Haromatic), 2879 (C-Haliphatic), 1442 (C-N), 1230 (P=O), 1064 (S=O), 1029 (P-O-Caliphatic);

1H-NMR (DMSO-d6) δ: 11.62 (2H, bs, 2 × NH), 7.10-8.58 (11H, m, Ar-H), 5.10-5.32 (1H, dd, J = 20 Hz and J = 10 Hz, P-CH-N), 3.90 (4H, m, 2 × -OCH2), 2.87 (6H, s, 2 × CH3), 1.37 (4H, m, 2 × CH2), 1.20 (4H, m, 2 × CH2), 0.71 (6H, m, 2 × CH3);

31P-NMR (δ, ppm): 23.12; MS: (m/z) 575 (M+•). Anal.Calcd for C27H38N5O5PS: C, 56.33; H, 6.65; N, 12.17. Found: C, 56.24; H, 6.59; N, 12.10. Dibutyl (4-nitrophenyl)(4-(N-pyrimidin-2-ylsulfamoy l)phenylamino)methylphosphonate (5j) IR(KBr) cm-1: 3367 (N-H), 2954 & 2931 (C-Haromatic), 2872 (C-Haliphatic), 1442 (C-N), 1220 (P=O), 1064 (S=O), 1036 (P-O-Caliphatic);


13C-NMR (δ ppm): 66.4 (C-2), 151.3 (C-4), 109.6 (C-5a&5b), 131.2 (C-6a&6b), 128.7 (C-7), 170.7 (C-10), 158.7 (C-12a&12b), 114.6 (C-13), 143.3 (C-3� ), 129.7 (C-4� & 8� ), 126.4 (C-5� & 7� ), 148.8 (C-6� ), 66.6 (2 × C-3�� ), 31.7 (C-4� � ), 17.9 (C-5 � � ), 13.1 (C-6 � � ); 31P-NMR (δ, ppm): 23.50; MS: (m/z) 577 (M+•). Anal.Calcd for C25H32N5O7PS: C, 51.99; H, 5.58; N, 12.13. Found: C, 51.90; H, 5.53; N, 12.06. Biological Activity Structure-activity relationships (SAR) of organophosphorus compounds (OPCs) Schrader [20] proposed that OPCs containing the main pharmacophore structural unit (I) exhibits significant biological activity.

Slight variation in structure I can have very drastic effects on the bioactive efficacy of OPCs due to the fact that the interaction of an enzyme/ virus/ bacteria/ fungi is very sensitive to the size, shape and polarity of the organophosphorus substrate molecules. Antibacterial Activity All the title compounds 5a-j were screened for their antibacterial activity against the growth of Staphylococcus aureus ATCC-25923 (Gram positive) and Escherichia coli ATCC-25922 (Gram negative) at three concentrations, 500, 250 and 100 µg/disc [21,22] in DMF (Table 1). The compounds were diluted in DMF for bioassay. Solvent control was included although no antibacterial activity has been noted in the solvent employed. The plates were incubated at 35 °C and examined for zone of inhibition around each disc after 12 h. The results were compared with the activity of the standard antibiotic Penicillin-G (250 µg/disc). They where showed moderate



antibacterial activity against both bacteria when compared with that of the standard compound. All samples were tested in triplicate and average results were recorded.

Table 1: Antibacterial activity of α-aminophosphonates (5a-j)

Compound

Zone of inhibition (mm)a Staphylococcus aureus Escherichia coli 100

µg/disc 250

µg/disc 500

µg/disc 100

µg/disc 250

µg/disc 250

µg/disc 5a 6 10 18 6 10 19 5b 6 9 15 5 10 16 5c 6 10 17 6 10 17 5d 5 10 16 5 11 18 5e 6 10 18 6 11 17 5f 6 9 16 6 11 19 5g 5 8 19 5 8 19 5h 6 9 19 6 10 19 5i 7 10 20 7 10 21 5j 8 11 21 8 11 23

bPenicillin-G 8 12 --- 8 14 --- aConcentration in ppm, bReference Compound

Antifungal Activity The compounds, 5a-j were screened for their antifungal activity (Table 2) against Aspergillus niger and Helminthosporium oryzae species along with standard fungicide Griseofulvin at three different concentrations (500, 250 and 100 ppm) in DMF [23]. Fungal cultures were grown on potato dextrose broth at 25 °C and finally spore suspension was adjusted to 105 spores/ mL. All the compounds 5a-j exhibited moderate to high antifungal activity when compared with that of the reference compound.

Table 2: Antifungal activitya of α-aminophosphonates (5a-j)

Compound

Zone of inhibition (mm)a Aspergillus niger Helminthosporium oryzae

100 µg/disc

250 µg/disc

500 µg/disc

100 µg/disc

250 µg/disc

500 µg/disc

5a 5 10 20 6 11 21 5b 5 8 17 5 9 18 5c 6 9 21 6 10 19 5d 7 10 20 6 12 21 5e 6 9 19 5 10 17 5f 7 10 22 7 13 22 5g 6 9 21 5 10 19 5h 6 10 20 5 10 20 5i 7 12 23 7 13 24 5j 8 14 25 8 14 25

bGriseofulvin 8 16 --- 8 16 --- aConcentration in ppm, bReference Compound

When compared with the reference compound Griseofulvin, all the compounds showed moderate to high antifungal activity against the growth of both the fungi. The majority of the compounds exhibited high activity against fungi. The compound 5j exhibited promising activity against Aspergillus niger and Helminthosporium oryzae and warrants further testing to determine their minimum inhibitory concentrations as well as their cytotoxicity.



CONCLUSION

From the above discussion, we concluded that the non-conventional microwave method in solvent-free and catalyst-free condition is the best methodology for synthesis of a new class of α-aminophosphonic acid esters in high yields (75-88%) in short times (8-10 min) by the addition of labile P-H to Schiff’s bases by Pudovik reaction. The anti-microbial activity of all the titled compounds showed moderate to high activity and the compounds 5b, 5d, 5h and 5j exhibited significant antibacterial activity, however, the compounds; 5c, 5e, 5f and 5g exhibited moderate to significant antifungal activities against all the employed organisms at conc. 500, 250 and 100 µg/disc (in ppm) and are comparable to that of standard drugs (Penicillin-G and Griseofulvin). Acknowledgments: The authors thank BRNS (DAE) BARC (Mumbai) for providing financial assistance (Sanction No.: 2307/ 37/ 46/ BRNS/ 2916; dated: 31-03-2008).

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