Synthesis of some novel imidazole-based dicationic carbazolophanes as potential antibacterials

Article abstract of DOI:10.1016/j.bmcl.2008.06.047

Synthesis of fluorescent imidazole-based dicationic carbazolophanes incorporating various spacer units is described. Interestingly, the cyclophanes 2a and 5a incorporating a pyridine moiety exhibited superior antibacterial activity against most of the pathogenic bacteria in the tested concentrations as compared to the other cyclophanes as well as the test control, benzalkonium chloride (BAC), cetylpyridinium chloride (CPC) and tetracycline.

Full text of DOI:10.1016/j.bmcl.2008.06.047

Bioorganic & Medicinal Chemistry Letters 18 (2008) 4416–4419
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis of some novel imidazole-based dicationic carbazolophanes
as potential antibacterials
a
b
b
Perumal Rajakumar a, , Karuppannan Sekar , Vellasamy Shanmugaiah , Narayanasamy Mathivanan
*
a Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
b Center for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai 600 025, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2008
Revised 5 May 2008
Accepted 13 June 2008
Available online 18 June 2008
Synthesis of fluorescent imidazole-based dicationic carbazolophanes incorporating various spacer units is
described. Interestingly, the cyclophanes 2a and 5a incorporating a pyridine moiety exhibited superior
antibacterial activity against most of the pathogenic bacteria in the tested concentrations as compared
to the other cyclophanes as well as the test control, benzalkonium chloride (BAC), cetylpyridinium chlo-
ride (CPC) and tetracycline.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Carbazolophanes
Quaternary ammonium compounds (QACs)
Antibacterial activity
Supramolecular systems with a fluorescence tag play an impor-
tant role in biology.1 Carbazole-based fluorophoric receptors find
application as phosphate2 and fluoride ion sensors3 and as fluores-
cence markers for cancer cells.4 Cyclophanes have received much
attention in the areas of host–guest complexation, molecular
self-assembly and specific receptor activity. Imidazole-based dicat-
ionic cyclophanes have been used for the synthesis of carbenoid5
and silver complexes6 and these also exhibit interesting conforma-
tional behavior.7 Amphiphilic quaternary ammonium compounds
(QACs)8 are generally known to be antibacterial substances due
to their electrostatic and hydrophobic interactions with negatively
charged bacterial membranes. In medicine, QACs such as benzalko-
nium chloride (BAC) and cetylpyridinium chloride (CPC) are still
broadly used as antibiotics. The synthesis and antimicrobial activ-
ity of various QACs including imidazolium and pyrrolidinonium
thol18 have been reported from our laboratory. However, to the
best of our knowledge, imidazole-based cationic macrocycles with
carbazole unit have not been reported. Herein, we wish to report
the synthesis and antibacterial activity of imidazole-based dicat-
ionic carbazolophanes 1–6.
The purpose of the synthesis of cationic carbazolophanes 1–6 is
to examine the antibacterial activity, due to their electrostatic and
hydrophobic interactions with negatively charged bacterial mem-
branes. Hence, antibacterial activity of the carbazolophanes 1–6b
was assayed against Proteus vulgaris, Proteus mirabilis, Pseudomonas
aeruginosa, Salmonella typhi and Staphylococcus aureus at different
concentrations.
The synthetic pathway leading to the synthesis of precyclo-
phane 10 and 11 is outlined in Scheme 1. Reaction of 1 equiv
of N-ethylcarbazole (7) with 2.1 equiv of p-toluoyl chloride in
the presence of AlCl3 in dry DCM at room temperature gave
the diketo compound 8 in 92% yield. NBS bromination of 8 in
the presence of Bz2O2 in dry CCl4 at reflux for 2 h gave the dibro-
mide 9 in 78% yield. The reaction of 2.1 equiv benzimidazole
with 1 equiv of dibromide 9 in 25% aq NaOH gave the precyclo-
phane 10 in 62% yield. Similarly the precyclophane 11 was also
obtained in 42% yield by the reaction of 2.1 equiv imidazole with
1 equiv of dibromide 9 in the presence of 25% aq NaOH. The
structure of precyclophanes 10 and 11 was also completely char-
acterized from spectral and analytical data.19,20 In the 1H NMR
spectrum of precyclophane 10, the –N–CH2– and –N@CH–N- pro-
tons of benzimidazole appeared as singlets at d 5.71 and d 9.32
and in the 13C NMR spectrum, the –N–CH2– carbon of benzimid-
azole and carbonyl carbon appeared at d 48.8 and d 195.2 in
addition to other carbons.
salts,9 4,40-(
a,x-polymethylenedithio)bis(1-alkylpyridinium io-
dide)s10 and fluorinated bis-ammonium salts11 are known in the
literature. Kawabata et al.12 have synthesized 30-(3-aminopyrazoli-
um)cephalosporins-based QACs which show good antibacterial
activity with Gram-positive and Gram-negative bacteria. Pernak
and Chwala et al.13 reported a quantitative relation between MIC
against bacteria and water–octanol partition coefficient (P) for cho-
line-like quaternary ammonium chlorides. Amphiphilc dendri-
mers14 and macrocyclic cavitand containing quaternary alkyl
ammonium groups at the periphery15 act as bactericidic agent with
high efficacy and good selectivity. Dicationic imidazolophanes with
various spacers like pyridine,16 m-terphenyl17 and chiral binaph-
* Corresponding author. Tel.: +91 44 22351269; fax: +91 44 22352494.
E-mail address: perumalrajakumar@hotmail.com (P. Rajakumar).
0960-894X/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2008.06.047

P. Rajakumar et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4416–4419
4417
Et
N
Y
O
O
R
X
Z
N
N
N
N
N
N
N
N
N
N
N
2Br
2Br
N
2Br
O
O
O
O
O
O
N
N
Et
Et
N
Et
1
2a meta X-Z = N, Y = H
3a R = H
2b para X = C, Z = OCH3, Y = OCH3
2c meta X = C, Z = OH, Y = NO2
3b R = COOH
Et
N
Y
O
O
R
X
Z
N
N
N
N
N
N
N
N
N
N
2Br
2Br
N
N
2Br
O
O
O
O
O
O
N
Et
N
Et
N
Et
4
5a meta X-Z = N, Y = H
6a R = H
5b para X = C, Z = OCH3, Y = OCH3
5c meta X = C, Z = OH, Y = NO2
6b R = COOH
Treatment of the precyclophane 10 with 1 equiv of dibromide
9 in CH3CN under reflux for 4 days afforded the carbazolophane
1 in 38% yield. The 1H NMR spectrum of carbazolophane 121 dis-
played two broad singlets at d 1.37 and d 4.57 for the methylene
and methyl protons of the N-Et unit, and a singlet at d 6.07 for
the –N–CH2– protons attached to the benzimidazole. The –N–
CH@N– protons appeared as a singlet at d 10.42 in addition to
the aromatic protons. In the 13C NMR spectrum, the N-Et car-
bons appeared at d 13.7 and d 38.1 and the –N–CH2– carbons
the other carbons. Similarly, the structure of other carbazolo-
phanes 2b–c, 3a–b was confirmed from spectral and analytical
data.27–29
By similar procedure, dicationic cyclophanes 4, 5a–c, 6a–b
were prepared in excellent yields by the reaction of 1 equiv of
the precyclophane 11 with one equiv of the dibromides 9, 12,
13, 14 and 15a–b in CH3CN under reflux for 4 days (Scheme
3). The structure of dicationic carbazolophanes 4, 5a–c and 6a–
b were completely characterized from spectral and analytical
data.30–34
attached to the benzimidazole unit at
d 49.7, a peak at d
194.7 for carbonyl carbon and in addition to the other aromatic
carbons.
Antibacterial activity: The antibacterial activity of the com-
pounds was evaluated against five human pathogenic bacteria
namely, P. vulgaris, P. mirabilis, P. aeruginosa, S. typhi and S. aur-
eus by the agar diffusion method. Among the carbazolophanes
1–6, the four cyclophanes namely, 2a, 2c, 5a and 5c exerted var-
ious levels of inhibitory effects against the pathogenic bacteria
(Table 1). Among 2a, 2c, 5a and 5c compound 2a exhibited sig-
nificant activity towards all the above mentioned bacteria fol-
lowed by compound 2c which also revealed remarkable
activity. The minimum inhibitory concentration (MIC) of com-
In order to test the synthetic utility of precyclophane 10 for the
synthesis of various dicationic carbazolophanes, one equiv of
precyclophane 10 was coupled with each one equiv of 2,6-bis(bro-
momethyl)pyridine (12),22 1,4-bis(bromomethyl)-2,5-dimethoxy-
benzene (13),23 1,3-bis-(bromomethyl)-4-nitrophenol (14),24 and
m-terphenyl dibromides 15a–b25 to give the carbazolophanes 2a,
2b, 2c, 3a and 3b in 42%, 44%, 41%, 38% and 33% yields, respec-
tively, after usual purification (Scheme 2).
The 1H NMR spectrum of carbazolophane 2a26 showed two
singlets at d 5.93 and d 5.95 for CH2– protons attached to N atom
of benzimidazole units. The benzimidazole –N–CH@N– protons ap-
peared as singlet at d 10.25 in addition to other protons of carba-
zole and imidazole unit. In the 13C NMR spectrum, the –N–CH2–
carbon attached to the benzimidazole unit at d 49.7 and d 50.9
and the carbonyl carbon appeared at d 195.0 and in addition to
pound 2a was determined between 8 and 20
12 and 30 g/ml for benzalkonium chloride (BAC), 18 and
42 g/ml for CPC and 15 and 35 g/ml for tetracycline. Carbazo-
lophane 5a and 5c also exhibited relatively better activity when
compare to the commercially available antibiotic like BAC, CPC
and tetracycline in inhibiting the growth of the above mentioned
bacteria. The antimicrobial activity35 of the test macrocycles was
lg/ml as against
l
l
l

4418
P. Rajakumar et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4416–4419
N
N
N
N
iii
R
R
O
O
N
Et
10
i
N
Et
O
O
N
N
N
7
N
Et
N
iv
8 R = H
9 R = Br
ii
O
O
N
Et
11
Scheme 1. Reagents and conditions: (i) AlCl3, p-toluoyl chloride, DCM(dry), rt, 8 h, 8 (92%); (ii) NBS, CCl4(dry), Bz2O2, 2 h, 9 (78%); (iii) benzimidazole, 25% NaOH, CH3CN, rt, 2
days, 10 (62%); (iv) imidazole, 25% NaOH, CH3CN, rt, 2 days, 11 (42%).
R
R
1
3a,b
Br15a R = H
Br
Br
15a R = H
15b R = COOH
Br
4
6a,b
15b R = COOH
9
9
i
i
i
i
NO2
NO2
10
N
11
N
Br
Br
Br OH Br
12
Br
Br
Br OH Br
12
14
i
14
i
i
OCH3
Br
2a
i
i
OCH3
Br
2c
5a
i
5c
Br
H3CO
13
Br
H3CO
13
2b
5b
Scheme 2. Reagents and conditions: (i) CH3CN, reflux, 4 days, 1 (38%), 2a (42%), 2b
(44%), 2c (41%), 3a (38%), and 3b (33%).
Scheme 3. Reagents and conditions: (i) CH3CN, reflux, 4 days, 4 (33%), 5a (47%), 5b
(41%), 5c (38%), 6a (35%), and 6b (31%).
Table 1
Antibacterial activity (minimum inhibitory concentration
dicationic carbazolophanes
lg/ml) of imidazolium
dose-dependent and it was remarkable at higher concentrations.
Other cyclophanes 1, 2b, 3a, 3b, 4, 5b, 6a and 6b were less
effective than 2a, 2c, 5a and 5c. Overall analysis of the antibac-
terial activity revealed that cyclophanes 1, 2a, 2c, 4, 5a and 5c
remarkably inhibited the growth of all the pathogenic bacteria
in most of the tested concentrations as compared to other com-
pounds and the control (Table 1).
In conclusion, the dicationic carbazolophanes 2a, 2c, 5a and 5c
with pyridine and nitro phenol spacer unit exhibited good antibac-
terial activity against all five human pathogenic bacteria. The com-
pounds 2a and 5a may be developed further as antibiotic drugs as
these showed better activity against all the test pathogens than the
other compounds. However, further studies are required to deter-
mine their potential against a wide range of human pathogens and
its mode of action. Syntheses of other similar dicationic carbazolo-
phanes and their antibacterial activity as well as molecular recog-
nition towards various biologically important anions are under
investigation.
Dicationic
P.
P.
P.
S.
S.
carbazolophanes
vulgaris
mirabilis
aeruginosa
typhi
aureus
1
2a
2b
2c
3a
3b
4
5a
5b
5c
6a
6b
30
15
45
35
50
60
40
25
60
30
70
65
28
30
35
NI
30
10
55
30
50
55
35
20
55
20
75
50
12
25
20
NI
35
20
70
30
65
70
55
30
80
35
75
80
30
42
35
NI
25
15
40
15
45
50
25
15
50
20
55
35
20
20
15
NI
26
8
NI
20
45
NI
25
12
75
20
75
35
15
18
20
NI
BAC
CPC
Tetracycline
Control
NI, no inhibition.

P. Rajakumar et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4416–4419
4419
27. Cyclophane 2b: Yield 44%; mp 262 °C; 1H NMR (400 MHz, DMSO-d6): d (ppm)
1.34 (br s, 3H); 3.85 (s, 6H); 4.56 (br s, 2H); 5.52 (s, 4H); 5. 69 (s, 4H); 7.52–8.37
(m, 22H); 8.73 (s, 2H); 10.66 (s, 2H). 13C NMR (100 MHz, DMSO-d6): d (ppm)
13.7, 37.4, 49.3, 56.2, 56.3, 113.8, 122.7, 123.1, 124.8, 126.1, 126.7, 127.0,
127.5, 128.1, 128.6, 129.4, 130.0, 130.3, 130.7, 131.0, 131.5, 137.9, 142.9, 151.3,
152.0, 194.8; m/z (FAB-MS) 987 (M+). Elemental Anal. Calcd for C54H45Br2N5O4:
C, 65.66; H, 4.59; N, 7.09. Found: 65.51; H, 4.47; N, 7.21.
Acknowledgments
The author thanks CSIR India, for financial assistance, DST-FIST
for providing NMR facility to the department and SAIF, CDRI Luc-
know, for providing FAB-MS spectra. K.S. thanks CSIR for SRF.
28. Cyclophane 2c: Yield 41%; mp 212–214 °C; 1H NMR (300 MHz, DMSO-d6): d
(ppm) 1.40 (br s, 3H, J = 7.2 Hz); 4.60 (q, 2H, J = 7.2 Hz); 5.93 (s, 4H); 6.01 (s,
4H); 7.62–8.48 (m, 23H); 8.73 (s, 2H); 10.53 (s, 2H). 13C NMR (75 MHz, DMSO-
d6): d (ppm) 13.7, 37.7, 49.4, 49.9, 113.2, 121.1, 122.1, 122.6, 124.7, 126.1,
126.4, 126.8, 127.2, 127.6, 128.1, 128.6, 129.0, 130.0, 130.6, 131.0, 131.8, 138.2,
142.2, 142.8, 194.8; m/z (FAB-MS) 988 (M+). Elemental Anal. Calcd for
References and notes
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T. C. Chem. Biodivers. 2004, 1, 1377.
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Commun. 2001, 1780.
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Bioorg. Med. Chem. 2004, 12, 853.
10. Ohkura, K.; Sukeno, A.; Yamamoto, K.; Nagamune, H.; Maeda, T.; Kourai, H.
Bioorg. Med. Chem. 2003, 11, 5035.
11. Massi, L.; Guittard, F.; Géribaldi, S.; Levy, R.; Duccini, Y. Int. J. Antimicrob. Agents
2003, 21, 20.
C52H40Br2N6O5: C, 63.17; H, 4.08; N, 8.50. Found: 63.29; H, 4.21; N, 8.63.
29. Cyclophane 3a: Yield 38%; mp >300 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.10 (br s, 3H); 4.31 (br s, 2H); 5.70 (s, 4H); 5.80 (s, 4H); 7.18–7.91 (m, 32H);
8.40 (s, 2H); 10.27 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm) 13.7, 37.7,
49.6, 49.8, 109.7, 114.1, 122.0, 123.7, 125.1, 126.1, 126.8, 127.0, 127.4, 127.5,
128.4, 128.6, 129.1, 129.2, 130.0, 130.2, 131.0, 131.1, 133.0, 137.8, 138.3, 140.0,
140.4, 142.6, 142.9, 194.7; m/z (FAB-MS) 1079 (M+). Elemental Anal. Calcd for
C64H49Br2N5O2: C, 71.18; H, 4.57; N, 6.49. Found: 71.31; H, 4.42; N, 6.62.
30. Cyclophane 4: Yield 33%; mp 263 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.37 (br s, 6H); 4.58 (br s, 4H); 5.63 (s, 8H); 7.52–8.06 (m, 28H); 8.74 (s, 4H);
9.60 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm) 13.7, 37.7, 51.7, 109.4,
120.0, 122.2, 123.1, 123.7, 128.1, 128.3, 128.7, 130.0, 136.8, 138.4, 143.0, 194.8;
m/z (FAB-MS) 1153 (M+). Elemental Anal. Calcd for C66H52Br2N6O4: C, 68.75; H,
4.55; N, 7.29. Found: 68.59; H, 4.37; N, 7.16.
31. Cyclophane 5a: Yield 47%; mp 298 °C; 1H NMR (400 MHz, DMSO-d6): d (ppm)
1.38 (br s, 3H); 4.62 (br s, 2H); 5.61 (s, 4H); 5.66 (s, 4H); 7.56 (d, 4H, J = 8 Hz);
7.64 (d, 2H, J = 7.6 Hz); 7.81–7.85 (m, 8H); 7.94 (d, 2H, J = 8.8 Hz); 8.02 (t, 1H,
J = 6.2 Hz); 8.12 (d, 2H, J = 8.8 Hz); 8.30 (s, 2H); 9.60 (s, 2H). 13C NMR (100 MHz,
DMSO-d6): d (ppm) 13.1, 37.3, 51.3, 52.7, 110.2, 120.9, 122.0, 122.4, 123.1,
123.6, 127.0, 127.7, 128.5, 129.3, 136.7, 137.5, 138.4, 142.5, 152.8, 194.2; m/z
(FAB-MS) 828 (M+). Elemental Anal. Calcd for C43H36Br2N6O2: C, 62.33; H, 4.38;
N, 10.14. Found: 62.47; H, 4.52; N, 10.28.
12. Ohki, H.; Kawabata, K.; Inamoto, Y.; Okuda, S.; Kamimura, T.; Sakane, K. Bioorg.
Med. Chem. 1997, 5, 557.
13. Pernak, J.; Chwala, P. Eur. J. Med. Chem. 2003, 38, 1035.
14. Chen, C. Z.; Cooper, S. L. Biomaterials 2002, 23, 3359.
15. Choi, J.; Kim, J.; Kim, K.; Yang, S. T.; Kima, J.; Jon, S. Chem. Commun. 2007, 1151.
16. Rajakumar, P.; Dhanasekaran, M. Tetrahedron 2002, 58, 1355.
17. Rajakumar, P.; Srisailas, M. Tetrahedron Lett. 1997, 38, 5323.
18. Rajakumar, P.; Selvam, S.; Dhanasekaran, M. Tetrahedron Lett. 2005, 46, 6127.
19. Precyclophane 10: Yield 62%; mp 142–144 °C; 1H NMR (400 MHz, CDCl3): d
(ppm) 1.43 (t, 3H, J = 7.2 Hz); 4.38 (q, 2H, J = 7.2 Hz); 5.71 (s, 4H); 7.18–7.36 (m,
10H); 7.45 (d, 2H, J = 8.8 Hz); 7.74 (d, 4H, J = 7.6 Hz); 7.83 (br s, 2H); 8.04 (d,
2H, J = 8.4 Hz); 8.39 (s, 2H); 9.32 (s, 2H). 13C NMR (100 MHz, DMSO-d6): d
(ppm) 13.7, 38.2, 48.8, 108.8, 110.2, 120.0, 121.7, 122.9, 123.0, 123.8, 123.9,
124.4, 125.2, 127.0, 129.0, 129.5, 130.5, 138.9, 139.1, 143.4, 195.2. (FAB-MS)
663 (M+). Elemental Anal. Calcd for C44H33N5O2: C, 79.62; H, 5.01; N, 10.55.
Found: 79.74; H, 5.16; N, 10.68.
32. Cyclophane 5b: Yield 41%; mp 223 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.37 (br s, 3H); 3.58 (s, 6H); 4.55 (br s, 2H); 5.36 (s, 4H); 5.62 (s, 4H); 6.99–7.98
(m, 18H); 8.72 (s, 2H); 9.62 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm) 13.7,
37.3, 48.2, 55.8, 56.2, 109.9, 122.1, 122.6, 123.1, 123.7, 125.4, 128.1, 129.2,
130.0, 130.3, 136.3, 137.4, 138.7, 142.5, 149.6, 151.2, 195.3; m/z (FAB-MS) 887
(M+). Elemental Anal. Calcd for C46H41Br2N5O4: C, 62.24; H, 4.66; N, 7.89.
Found: 62.41; H, 4.47; N, 7.72.
33. Cyclophane 5c: Yield 38%; mp 223 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.36 (t, 3H, J = 7.1 Hz); 4.63 (q, 2H, J = 7.1 Hz); 5.62 (s, 4H); 5.66 (s, 4H); 7.56–
7.64 (m, 4H); 7.79–7.93 (m, 15H); 8.71 (s, 2H); 9.50 (s, 2H). 13C NMR (75 MHz,
DMSO-d6): d (ppm) 13.7, 37.7, 51.2, 51.3, 109.6, 120.3, 122.1, 122.2, 123.7,
127.1, 128.2, 128.6, 129.2, 129.8, 130.0, 130.3, 135.6, 137.9, 138.3, 138.7, 142.9,
194.8; m/z (FAB-MS) 888 (M+). Elemental Anal. Calcd for C44H36Br2N6O5: C,
59.47; H, 4.08; N, 9.46. Found: 59.61; H, 4.23; N, 9.57.
20. Precyclophane 11: Yield 42%; mp 122–123 °C; 1H NMR (400 MHz, CDCl3): d
(ppm) 1.41 (t, 3H, J = 7.2 Hz); 4.36 (q, 2H, J = 7.2 Hz); 5.16 (s, 4H); 6.90 (br s,
2H); 7.04 (br s, 2H); 7.18 (d, 4H, J = 7.2 Hz); 7.40 (d, 2H, J = 8.4 Hz); 7.58 (br s,
2H); 7.70 (d, 4H, J = 7.6 Hz); 7.92 (d, 2H, J = 8.4 Hz); 8.46 (s, 2H). 13C NMR
(100 MHz, DMSO-d6): d (ppm) 13.7, 38.1, 50.3, 108.9, 119.4, 122.6, 123.5,
126.1, 126.9, 128.9, 130.4, 137.5, 138.3, 139.9, 143.2, 195.4; (FAB-MS) 563
(M+). Elemental Anal. Calcd for C36H29N5O2: C, 76.71; H, 5.19; N, 12.43. Found:
76.86; H, 5.31; N, 12.56.
34. Cyclophane 6a: Yield 35%; mp >300 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.35 (br s, 3H); 4.54 (br s, 2H); 5.53 (s, 4H); 5.61 (s, 4H); 7.54–8.01 (m, 28H);
8.68 (s, 2H); 9.64 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm) 13.7, 37.7,
51.7, 51.8, 109.7, 122.1, 122.8, 123.1, 125.1, 126.1, 127.0, 127.4, 128.3, 128.6,
129.1, 129.2, 129.6, 130.1, 130.2, 136.1, 138.4, 139.9, 140.4, 142.9, 194.7; m/z
(FAB-MS) 979 (M+). Elemental Anal. Calcd for C56H45Br2N5O2: C, 68.65; H, 4.63;
N, 7.15. Found: 68.78; H, 4.72; N, 7.28.
35. Antibacterial activity: The cultures of human pathogenic bacteria P. vulgaris, P.
mirabilis, P. aeruginosa, S. typhi and S. aureus used in this study were obtained
from the Culture Collections of Biocontrol and Microbial Metabolites
Laboratory, Centre for Advanced Studies in Botany, University of Madras and
maintained on Nutrient Agar (NA), consisting of the following [(g/L) Beef
extract 1.0; Yeast extract 2.0; Peptone 5.0; NaCl 5.0; Agar 15.0; Distilled H2O
1 L; pH 7.2.] in slants or Petriplates at room temperature (28 2 °C). The
antibacterial activity of the compounds against human pathogens was
evaluated by the agar diffusion method. About 1 ml of inoculum of each test
pathogen was added to the molten Nutrient Agar (NA) medium and poured
into sterile Petriplates under aseptic conditions. After solidification, a 5-mm
well was made in the centre of each plate using a sterile cork borer. Each
compound was dissolved in 10% DMSO to get different concentrations and
21. Cyclophane 1: Yield 38%; mp 274 °C; 1H NMR (300 MHz, DMSO-d6): d (ppm)
1.37 (br s, 6H); 4.57 (br s, 4H); 6.07 (s, 8H); 7.35–8.10 (m, 32H); 8.73 (s, 4H);
10.42 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm) 13.7, 38.1, 49.7, 114.0,
121.5, 122.1, 123.7, 125.5, 126.0, 126.9, 128.3, 128.6, 130.0, 131.1, 137.6, 138.4,
142.9, 194.7; m/z (FAB-MS) 1253 (M+). Elemental Anal. Calcd for
C
74H56Br2N6O4: C, 70.93; H, 4.50; N, 6.71. Found: 70.81; H, 4.63; N, 6.84.
22. Newcomb, M.; Timko, J. M.; Walba, D. M.; Cram, D. J. J. Am. Chem. Soc. 1977, 99,
6392.
23. Nair, M. S.; Sudhir, U.; Joly, S.; Rath, N. P. Tetrahedron 1999, 55, 7653.
24. Demendoza, J.; Nieto, P. M.; Prados, P.; Sanchez, C. Tetrahedron 1990, 6, 671.
25. Hart, H.; Rajakumar, P. Tetrahedron 1995, 51, 1313.
26. Cyclophane 2a: Yield 42%; mp 300–302 °C; 1H NMR (300 MHz, DMSO-d6): d
(ppm) 1.39 (t, 3H, J = 7.2 Hz); 4.62 (q, 2H, J = 7.2 Hz); 5.93 (s, 4H); 5.95 (s, 4H);
7.33–7.46 (s, 4H); 7.69–7.83 (m, 16H); 7.95 (d, 2H, J = 9.3 Hz); 8.09 (t, 1H,
J = 7.5 Hz); 8.18 (s, 2H); 10.25 (s, 2H). 13C NMR (75 MHz, DMSO-d6): d (ppm)
13.8, 37.1, 49.7, 50.9, 110.8, 113.8, 114.0, 121.0, 123.3, 124.1, 126.2, 126.3,
127.6, 128.5, 128.7, 129.8, 130.5, 131.4, 137.4, 138.5, 139.1, 142.9, 153.0,
195.0; m/z (FAB-MS) 928 (M+). Elemental Anal. Calcd for C51H40Br2N6O2: C,
65.96; H, 4.34; N, 9.05. Found: 65.82; H, 4.24; N, 9.18.
filter was sterilized using 0.25 lm filter paper. Each well received 50 lL
solution of each compound and the plates were incubated at room
temperature. Sterile DMSO (10%) was used as control. After 48 h, the
appearance of inhibition zone around the well was observed.