R. Dhanapal et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3599–3603
3601
To begin with, chalcone 1j was prepared as in the general
procedure and treated with 2-ethylfuran 2 in acetonitrile in the
Table 2
Minimum inhibitory concentration
presence of boron trifluoride diethyl etherate at room tempera-
Entry
Minimum inhibitory concentration (MIC) (mg/ml)
1
0
ture. The reaction took place regioselectively to yield the title
compound 3j (Scheme 1, Table 1, entry 10). To demonstrate the
methodology applicable to a variety of substrates having bromo,
fluoro, cyano, nitro and alkyl substitutions, synthesis of several fur-
an derived oxabicyclics have also been synthesised and the results
are shown in Table 1. For these cycloaddition reactions there are
two regioisomers possible, via structures A and B for 3j. (Fig. 1)
B. subtilus
V. cholera
K. pneumonia
S. aureus
E. coli
3
3
3c
a
b
0.312
0.322
0.625
0.156
1.25
0.312
0.078
0.625
0.625
1.25
1.25
1.25
1.25
0.625
0.312
0.125
1.25
0.004
0.156
0.625
0.156
0.625
0.156
0.078
0.312
0.312
0.625
0.625
0.625
0.312
0.625
0.156
0.007
0.625
0.625
1.25
0.156
1.25
0.156
1.25
0.625
0.625
1.25
1.25
1.25
0.625
1.25
0.031
0.015
0.312
0.312
0.625
0.156
1.25
0.312
0.078
0.625
0.625
1.25
1.25
1.25
1.25
0.625
0.312
0.062
0.625
0.625
1.25
3d
3
3
3
3
3i
3j
3
3
3
e
f
g
h
1.25
0.625
0.312
0.625
0.625
0.625
0.625
0.625
0.625
0.625
0.625
0.015
2
The regioisomers can be identified using D NMR HMBC experi-
ments. If structure A is favoured, three 3J couplings are possible
for the carbonyl carbon, whereas for the structure B, only two such
correlations will appear. Experimentally, we observed three corre-
lations (Fig. 3S in Supporting information). This clearly indicated
k
l
m
that the regioselectivity is favoured towards the structure A. The
3n
3o
structures of compounds 3a–o were confirmed by IR, 1H and
13
C
Ciprofloxacin
NMR spectroscopy, mass spectrometry and elemental analysis.
1
The H NMR spectrum of compound 3j consist of a characteristic
doublet of doublet due to the proton Ha at d 3.50 (J = 5.35,
1
1
6.8 Hz), a doublet due to the proton Hb at d 3.75 (J = 8.40,
6.8 Hz) and a multiplet Hc at d 3.27–5.30. To investigate the scope
Table 3
DPPH antioxidant scavenging activity
of this reaction, a series of furan derived oxabicyclic compounds
were synthesized and characterized (Table 1, entries 1–15). All
the prepared compounds gave excellent yields (85–92%).
Entry
Compounds
Inhibition of free radicals (%)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
BHT
58.9
35.5
42.4
58.9
21.6
30.5
32.6
36.0
33.4
22.2
17.7
18.1
22.3
15.1
23.2
58.4
All the newly synthesised compounds (3a–o) were screened for
their antibacterial and antioxidant activities. The in vitro antibac-
terial and antioxidant activities of the synthesized 3a–o are tabu-
lated (Tables 2 and 3) and represented as a graph in Figure 2.
Antimicrobial studies: The antibacterial tests were conducted
against five human bacterial pathogens such as Vibrio cholera,
Bacillus subtilus, Klebsiella pneumoniae, Staphylococcus aureus and
Escherichia coli and the activities of the compounds were deter-
10
11
12
13
11
mined by means of microdilution broth assay method with mod-
ifications reported by Sarker et al.12 using resazurin as an indicator.
1
1
1
4
5
6
In this method instead of resazurin dye, 2,3-bis[2-methoxy-4-ni-
tro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt
(
XTT) is used as the indicator for the growth of bacteria or inhibi-
13
tion of bacterial growth. This modification is very easy, simple to
execute and sensitive method compare to the normal methods to
predict the MIC (minimum inhibitory concentration) values.
1
4,15
compounds along with a control, DMSO. The plates were then
incubated at 37 °C for 24 h, and after incubation the diameter of
zone of inhibition in mm was measured.
Through these assay methods, it was found that the oxabicyclo
heptenyl derivatives have moderate to good antibacterial activity
for various human pathogens. Except for S. aureus and K.
pneumoniae, compound 3g showed the lowest minimum inhibitory
concentration for B. subtillus, E. coli, and V. cholera. For K.
pneumoniae, 3a showed the lowest MIC that is better than the stan-
dard ciprofloxacin. With respect S. aureus, 3o found to have an
These MIC values (in mg/ml) of bacterial pathogens for the above
mentioned oxabicyclo derivatives were compared with a control
antibiotic sample, ciprofloxacin. Apart from this microdilution
method, well diffusion assay16 was also carried out in the determi-
nation of the antibacterial activity. For the well diffusion assay,
1
7 h old bacterial cultures were grown over the surface of a dried
Muller Hinton agar plates using a sterile cotton swab and allowed
to absorb in the agar for 10 min. Then the well was cut using a cork
borer and loaded with different concentrations of the synthesized
Cl
H
O
O
O
H
c
H
c
H
b
Ha
H
b
O
H
a
H
Cl
B
A
Figure 1. Possible regioisomers in the oxabicyclo compound 3j.