Supplementary Information

Antimicrobial efficacy of synthetic pyranochromenones and (coumarinyloxy)acetamides

Abhishek K. Singh,a Suchita Prasad,a Bipul Kumar,b Shiv Kumar,a

Amitesh Anand,b Shashank S. Kamble,bSunil K. Sharmaa,*and

Hemant K. Gautamb,*

aDepartment of Chemistry, University of Delhi, Delhi 110007, India

bCSIR-Institute of Genomics and Integrative Biology, Sukhdev Vihar, Mathura Road,

Delhi 110025, India

List of Contents

Table S1. Zone of inhibition (mm) of compounds (1, 2, 4 and 6)against resistant pathogenic bacterial strains.

Figure S1. Cytotoxicity evaluation of compound 1 on viability of A549 cell line by MTT assay.

Figure S2.1H & 13C NMR of N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1).

Figure S3.1H & 13C NMR of N,N,N-triethyl-6-(10-hydroxy-4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-3-yl)hexan-1-aminium bromide (2).
Figure S4.1H & 13C NMR of N-(3-(dibutylamino)propyl)-2-((3-ethyl-4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetamide (4).
Figure S5.1H & 13C NMR of N-(3-(dimethylamino)propyl)-2-((3-hexyl-4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetamide (6).
Table S1. Zone of inhibition (mm) of compounds 1, 2, 4 and 6 against resistant pathogenic bacterial strains.
Compound / Staphylococcus aureus / Pseudomonas aeruginosa / Salmonella
enteritidis
1 / 20 / 19 / 11
2 / 14 / 14 / ˂10
4 / 10 / 12 / 11
6 / 15 / 14 / 10
Gentamicin / 18 / 25 / 26
Neomycin / 12 / 14 / 16
Vancomycin / 22 / ˂10 / 11
Diameter of zone of inhibition (mm) including disc diameter of 6 mm; Concentration of compound = 250 µg/disc.

Figure S1. Cytotoxicity evaluation of compound 1 on viability of A549 cell line by MTT assay.

Data and characterizations

N,N,N-Triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1):Rf: 0.41 (MeOH:CHCl3 :: 1:4); UV (MeOH) λmax: 260 nm and 328 nm; IR(KBr) νmax: 3412.46, 2933.91, 1718.29 (C=O), 1609.88, 1568.95, 1399.37, 1108.57, 1054.36, 937.64, 887.63, 792.37, 585.05 cm-1; 1H NMR(400MHz, CDCl3): δ 1.30-1.43 (m, 23H, H-4 – H-7, 2 x C-8ꞌ CH3 & 3 x H-2ꞌꞌ), 1.46-1.57 (m, 2H, H-3), 1.67-1.87 (m, 8H, H-2, H-8, H-9 & H-7ꞌ), 2.36 (s, 3H, C-4ꞌ CH3), 2.84 (t, 2H, J = 6.59 Hz, H-6ꞌ), 3.21-3.28 (m, 2H, H-1), 3.50 (q, 6H, J = 7.32 Hz, 3 x H-1ꞌꞌ), 4.05 (t, 2H, J = 6.59 Hz, H-10ꞌ), 6.07 (s, 1H, H-3ꞌ), 7.03 (s, 1H, H-5ꞌ) ppm; 13C NMR(100.5 MHz CDCl3): 8.18 (C-2ꞌꞌ), 18.93 (C-4ꞌ CH3), 27.03 (2 x C-8ꞌ CH3), 22.01, 22.47, 25.93, 26.42, 29.04, 29.12, 29.28, 29.30, 30.17 (C-2 – C-9 & C-6ꞌ), 32.48 (C-7ꞌ), 53.60 (C-1ꞌꞌ), 57.64 (C-1), 73.97 (C-10), 75.92 (C-8ꞌ), 111.87 (C-3ꞌ), 113.32 (C-12ꞌ), 118.62 (C-14ꞌ), 119.11 (C-5ꞌ), 134.93 (C-10ꞌ), 146.38 (C-11ꞌ), 150.92 (C-13ꞌ), 153.03 (C-4ꞌ), 161.36 (C-2ꞌ) ppm; HRMS: m/z [M]+ Calculated for C31H50NO4+: 500.3740; found: 500.3753.

N,N,N-Triethyl-6-(10-hydroxy-4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-3-yl)hexan-1-aminium bromide (2):Rf: 0.38 (MeOH:CHCl3 :: 1:4); UV (MeOH) λmax: 264 nm and 329 nm; IR(KBr) νmax: 3387.59, 2927.26, 2854.88, 1698.02 (C=O), 1619.60, 1579.03, 1467.63, 1390.63, 1370.34, 1122.01, 1054.68, 938.90, 753.43, 660.97 cm-1; 1H NMR(400MHz, CDCl3): δ 1.16.1.44 (m, 23H, H-2 – H-5, 2 x C-8 CH3 & 3 x H-2ꞌꞌ), 1.80 (t, 2H, J = 6.59 Hz, H-7ꞌ), 2.27 (s, 3H, C-4ꞌ CH3), 2.51 (t, 2H, J = 7.69 Hz, H- 6), 2.78 (t, 2H, J = 6.59 Hz, H- 6ꞌ), 3.21-3.30 (m, 2H, H-1) 3.40-3.50 (m, 6H, H-1ꞌꞌ), 6.81 (s, 1H, H-5ꞌ) ppm; 13C NMR(100.5 MHz CDCl3): δ 8.15 (C-2ꞌꞌ), 15.16 (C-4ꞌ CH3), 21.74 (C-6ꞌ), 22.27 (C-6), 27.01 (2 x C-8 CH3), 25.98, 27.09, 28.17, 28.63 (C-2 – C-5), 32.87 (C-7ꞌ), 53.56 (C-1ꞌꞌ), 57.65 (C-1), 76.52 (C-8ꞌ), 114.04 (C-12ꞌ), 115.04 (C-5ꞌ), 117.76 (C-14ꞌ), 123.07 (C-3ꞌ), 132.06 (C-10ꞌ), 138.98 (C-11ꞌ), 143.66 (C-4ꞌ), 147.23 (C-13ꞌ), 161.85 (C-2ꞌ) ppm; HRMS: m/z [M]+ Calculated for C27H42NO4+: 444.3114; found: 444.3118.

N-(3-(Dibutylamino)propyl)-2-((3-ethyl-4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetamide (4):M. Pt.:121.3-130.0 oC; Rf: 0.42 (MeOH:CHCl3 :: 1:49); UV (MeOH) λmax: 292 nm and 318 nm;IR(KBr) νmax: 3371.69 (N-H str), 2957.40, 1712.48 (C=O), 1661.03 (NHCO-), 1618.49, 1546.92, 1160.04, 1095.98, 870.93, 777.91, 599.61 cm-1; 1H NMR(400 MHz, CDCl3): δ 0.82 (t, 6H, J = 7.32 Hz, H-4ꞌꞌꞌꞌ), 1.12 (t, 3H, J = 7.36 Hz, H-2"ꞌ), 1.16-1.26 (m, 4H, H-3ꞌꞌꞌꞌ), 1.32-1.39 (m, 4H, H-2ꞌꞌꞌꞌ), 1.63-1.69 (m, 2H, H-2ꞌꞌ), 2.34 (t, 4H, J = 8.08 Hz, H-1ꞌꞌꞌꞌ), 2.37 (s, 3H, C-4ꞌ CH3), 2.50 (t, 2H, J = 6.24 Hz, H-3ꞌꞌ), 2.65 (q, 2H, J = 7.32 Hz, H-1ꞌꞌꞌ), 3.41-3.47 (m, 2H, H-1"), 4.51 (s, 2H, H-2), 6.80 (d, 1H, J = 2.20 Hz, H-8ꞌ), 6.84 (dd, 1H, J = 2.92 Hz & 8.76 Hz, H-6ꞌ), 7.52 (d, 1H, J = 8.80 Hz, H-5ꞌ), 8.26 (brs, 1H, NH) ppm; 13C NMR(100.5 MHz, CDCl3): δ 13.22 (C-2ꞌꞌꞌ), 14.20 (C-4ꞌꞌꞌꞌ), 14.70 (C-4ꞌ CH3), 20.87 (C-3ꞌꞌꞌꞌ), 21.00 (C-1"ꞌ), 25.60 (C-2"), 28.91 (C-2ꞌꞌꞌꞌ), 39.91 (C-1"), 53.58 (C-3"), 54.24 (C-1""), 67.82 (C-2), 102.43 (C-8ꞌ), 111.44 (C-6ꞌ), 115.51 (C-10ꞌ), 125.87 (C-3ꞌ), 125.92 (C-5ꞌ), 145.57 (C-4ꞌ), 153.64 & 159.33 (C-9ꞌ & C-7ꞌ), 161.82 & 167.27 (C-2ꞌ & C-1) ppm; HRMS: m/z [M + Na]+Calculated for C25H38N2O4: 453. 2729; found: 453.2729.

N-(3-(Dimethylamino)propyl)-2-((3-hexyl-4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetamide (6):M. Pt.:136.0-137.1 oC; Rf: 0.47 (MeOH:CHCl3 :: 1:49); UV (MeOH) λmax: 318 nm; IR(KBr) νmax:3373.96 (N-H str), 2923.56, 1709.94 (C=O), 1662.74 (NHCO-), 1618.85, 1550.06, 1430.12, 1285.53, 1162.34, 1090.23, 871.91, 780.88, 601.50 cm-1; 1H NMR(400MHz, CDCl3): δ 0.88 (t, 3H, J = 6.96 Hz, H-6"ꞌ), 1.29-1.31 (m, 4H, H-4ꞌꞌꞌ & H-5ꞌꞌꞌ), 1.36-1.41 (m, 2H, H-3ꞌꞌꞌ), 1.47-1.54 (m, 2H, H-2"ꞌ), 1.66-1.70 (m, 2H, H-2"), 2.18 (s, 6H, H-1""), 2.38 (s, 3H, C-4ꞌ CH3), 2.39 (t, 2H, J = 5.86 Hz, H-3"), 2.62 (t, 2H, J = 8.05 Hz, H-1"ꞌ), 3.42-3.47 (m, 2H, H-1"), 4.51 (s, 2H, H-2), 6.80 (d, 1H, J = 2.20 Hz, H-8ꞌ), 6.83 (dd, 1H, J = 2.20 Hz & 8.79 Hz, H-6ꞌ), 7.53 (d, 1H, J = 8.79 Hz, H-5ꞌ), 8.33 (brs, 1H, NH) ppm; 13C NMR(100.5 MHz, CDCl3): δ 14.02 (C-6ꞌꞌꞌ), 14.79 (C-4ꞌ CH3), 22.56 (C-5"ꞌ), 25.43 (C-2"), 27.53 (C-4"ꞌ), 28.70 (C-3"ꞌ), 29.31 (C-2"ꞌ), 31.64 (C-1"ꞌ), 39.43 (C-1"), 45.34 (C-1""), 58.86 (C-3"), 67.46 (C-2), 102.15 (C-8ꞌ), 111.06 (C-6ꞌ), 115.30 (C-10ꞌ), 124.57 (C-3ꞌ), 125.73 (C-5ꞌ), 145.56 (C-4ꞌ), 153.43 & 159.06 (C-9ꞌ & C-7ꞌ), 161.74 & 167.08 (C-2ꞌ & C-1); HRMS: m/z [M + Na]+Calculated for C23H34N2O4: 425.2416; found: 425.2402.

Figure S2. 1H & 13C NMR spectra of N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydro

pyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1).

Figure S3. 1H & 13C NMR spectra of N,N,N-triethyl-6-(10-hydroxy-4,8,8-trimethyl-2-oxo-2,6,7,8-

tetrahydropyrano[3,2-g]chromen-3-yl)hexan-1-aminium bromide (2).

Figure S4. 1H & 13C NMR spectra of N-(3-(dibutylamino)propyl)-2-((3-ethyl-4-methyl-2-oxo-2H-

chromen-7-yl)oxy)acetamide (4).

Figure S5. 1H & 13C NMR spectra of N-(3-(dimethylamino)propyl)-2-((3-hexyl-4-methyl-2-oxo-2H-

chromen-7-yl)oxy)acetamide (6).