S. A. Kotharkar, D. B. Shinde / Bioorg. Med. Chem. Lett. 16 (2006) 6181–6184
6183
In spite of the scarce number of compounds tested this
preliminary study evidences that the substituents on
both quinoxaline and coumarin moieties exert signifi-
cant influence on antimicrobial activities.
Washed with cold chloroform to give 2a. All other
compounds of this series were synthesized by following
the above procedure.
2
,9,10-Trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4-b]
quinoxalines (4a–4n): A solution of equimolar amount of
0.01 mol) of 3-bromo-4-hydroxycoumarin (2a–2e) and
appropriate diamine in ethanol (25 ml) was refluxed for 4–
h. The reaction was monitored by TLC. After comple-
(
Furthermore, in comparison with antibiotics commonly
used in therapy, our most potent compound (4j) shows
comparable (although less potent) activities. Further
studies are in progress to optimize these lead compounds
and to characterize the mode of action.
6
tion of reaction, reaction mixture was cooled and poured
into crushed ice. The crude compounds were purified by
recrystallization with diethyl ether–hexane or by silica gel
column chromatography to afford pure desired com-
pounds. All other compounds of this series were synthe-
sized by following the above procedure. The physical data
of these compounds have been recorded in Table 1.
Acknowledgments
6
-Oxo-7,12-dihydro-chromeno [3,4-b]quinoxalines (4a):
1
Authors are thankful to Head, Department of Chemical
Technology, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad, (M.S.) India, for providing
necessary laboratory facility. Also Mr. Bipinchandra
K. Salunke, School of Life Sciences, North Maharashtra
University, Jalgaon, (M.S.), India, for helping in antimi-
crobial activity.
6
H NMR (DMSO-d ) :d = 4.02 (2H, br s, NH), 6.20
(2H, m, H-8,11), 6.34 (2H, m, H-9,10), 7.20 (1H, m, H-2),
7.25 (1H, m, H-4), 7.40 (H, m, H-3), 7.60 (1H, m, H-1).
1
3
2
CNMR (50 MHz [ H
27.1, 126.2, 125.4, 124.1, 120.2, 118.2, 114.7, 102.1.
Mass (ES/MS) : m/z 249 (M-H).
-Methyl-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxa-
6
] DMSO) d: 161, 149.2, 132.1, 131,
1
2
1
lines. (4b): H NMR (DMSO-d
(
6
) :d = 2.29 (3H, s), 4.01
2H, br s, NH), 6.20 (2H, m, H-8,11), 6.34 (2H, m,
H-9,10), 7.01 (1H, d, H-4), 7.18 (1H, d, H-3), 7.35 (1H, d,
H-1).
References and notes
1
3
2
6
CNMR (50 MHz [ H ] DMSO) d = 161, 147.1, 133.8,
1
. Dell, A.; William, D. H.; Morris, H. R.; Smith, G. A.;
Feeney, J.; Roberts, G. C. K. J. Am. Chem. Soc. 1975, 97,
133.2, 132.6, 127.6, 126.8, 118.6, 115.0, 102, 20.8.
Mass (ES/MS): m/z 263 (M-H).
2-Methoxy-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxa-
2
. Bailly, C.; Echepare, S.; Gago, F.; Waring, M. J. Anti-
497.
1
lines. (4c): H NMR (DMSO-d
2
3
4
5
6
7
8
9
6
):d = 4.01 (2H, br s, NH),
3.25 (3H, s), 6.20 (2H, m, H-8,11), 6.34 (2H, m, H-9,10),
Cancer Drug Des. 1999, 15, 291.
. Sato, S.; Shiratori, O.; Katagiri, K. J. Antibiot. 1967, 20,
2
6.88 (1H, d, H-3), 7.01 (1H, d, H-4), 7.10 (1H, d, H-1).
1
3
2
70.
. Sakata, G.; Makino, K.; Kurasawa, Y. Heterocycles 1998,
7, 2481.
. Ali, M. M.; Ismail, M. M. F.; El-Gabby, M. S. A.;
Zahran, M. A.; Ammar, T. A. Molecules 2000, 58, 64.
. Kaneko, C.; Katagiri, S.; Japan Kokai Tokkyo Koho JP,
6
CNMR (50 MHz [ H ] DMSO) d: 161, 157.2, 142.1,
132.1, 131, 129.6, 121.1, 118.2, 118.1, 114.8, 112.6, 111,
101.1, 54.8.
2
Mass (ES/MS): m/z 279 (M-H).
2-Bromo-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines
1
(4d): H NMR (DMSO-d
): d = 4.01 (2H, br s, NH), 6.19
6
1
988, 62, 264. Chem. Abstr., 1988, 109, 231061.
(2H, m, H-8,10), 6.31 (2H, m, H-9,10), 7.01 (1H, d, H-4),
7.58 (1H, d, H-3), 7.72 (1H, d, H-1).
. Sarges, R.; Howard, H. R.; Browne, R. C.; Label, L. A.;
Seymour, P. A. J. Med. Chem. 1990, 33, 2240.
. Kinashi, H.; Otten, S. L.; Dunkan, J. S.; Hutchinson, C.
R. J. Antibiot. 1988, 41, 624.
1
3
2
6
CNMR (50 MHz [ H ] DMSO) d = 161, 148.9, 132.5,
132.4, 131.3,130.7, 129.07, 129.3, 122.8, 118.9, 118.5, 115,
102.8.
. Stahmann, M. A.; Ikawa, M.; Link, K. P.; US Patent,
1
Mass (ES/MS): m/z 328 (M-H).
2-Chloro-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines
947, 2, 427; Chem. Abstr. 42, 1948, 6034.
0. Mitra, J.; Mitra, A. K. Indian J.Chem. 1992, 31, 693.
1. Carrod, L. P.; Grady, F. D. Antibiotics and Chemotherapy,
1
(4e): H NMR (DMSO-d
1
1
): d = 4.01 (2H, br s, NH), 6.19
6
(2H, m, H-8,10), 6.31 (2H, m, H-9,10), 7.08 (1H, d, H-4),
7.40 (1H, d, H-3), 7.58 (1H, d, H-1).
3
rd ed.; Churchill Livingstone: Edinburgh, 1972, p. 477.
2. El-Deen, I. M.; Abd El-Fattah, M. E. Serb. Chem. Soc.
000, 65, 95.
3. Experimental: Melting points are uncorrected. H and
NMR spectra were recorded on a Varian Gemini
00 MHz spectrometer. Chemical shifts d (ppm) relative
1
3
2
1
1
CNMR (50 MHz [ H ] DMSO) d = 161, 147.3, 132.2,
6
2
131.1, 129.6, 127.8, 126.8, 121.9, 118.6, 115, 102.8.
Mass (ES/MS): m/z 283 (M-H).
2-Fluoro-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines
1
13
C
1
(4f): H NMR (DMSO-d
2
): d = 4.03 (2H, br s, NH), 6.19
6
to TMS as an internal standard are reported. Electron
spray ionization mass spectra (ESI-MS) were recorded on
a Water-Micromass Quattro-II spectrometer. All of the
reagents used were of AR grade and used without further
purification. Column chromatography employed silica gel
of 60–120 mesh.
General procedure: 3-Bromo-6-substituted-4-hydroxy-
coumarins (2a–2g) A mixture of 0.01 mol of 4-hydroxy-
coumarin in 50 ml of chloroform in a 250 ml flask. Cool it
in an ice water bath. Add very slowly with constant
stirring (about 15 min) from a dropping funnel 0.01 mol of
bromine, stir the mixture by keeping the temperature
below 10 °C, and keep it overnight. 3-Bromo-4-hydroxy-
coumarin commences as white needles. Filter and dry it.
(2H, m, H-8,10), 6.31 (2H, m, H-9,10), 7.08 (1H, d, H-4),
8.10 (1H, d, H-3), 8.32 (1H, d, H-1).
CNMR (50 MHz [ H ] DMSO) d = 155.1, 142.4, 132.2,
6
1
3
2
131.1, 129.6, 127.8, 126.8, 121.9, 118.6, 114.8, 102.8.
Mass (ES/MS): m/z 267 (M-H).
2-Nitro-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines
1
(4g): H NMR (DMSO-d
): d = 4.03 (2H, br s, NH), 6.19
6
(2H, m, H-8,10), 6.31 (2H, m, H-9,10), 7.08 (1H, d, H-4),
8.10 (1H, d, H-3), 8.32 (1H, d, H-1).
1
3
2
6
CNMR (50 MHz [ H ] DMSO) d = 163.1, 158.4, 145.2,
131.1, 129.6, 127.8, 126.8, 121.9, 118.6, 114.8, 102.8.
Mass (ES/MS): m/z 294 (M-H).
9,10-Dimethyl-6-oxo-7,12-dihydro-chromeno[3,4-b]quinox-
1
alines (4h): H NMR (DMSO-d
): d = 2.31 (6H, S), 4.08
6