Synthesis and antimicrobial activity of some bisoctahydroxanthene-1,8-dione derivatives

Article abstract of DOI:10.1007/s00044-010-9459-2

The bisoctahydroxanthen-1,8-dione derivatives were synthesized effectively via p-dodecylbenzene sulfonic acid the catalysed cyclocondensation of cyclic 1,3-dicarbonyl compounds with 1,3- or 1,4-benzene dicarboxaldehydes in water. The products were obtaine

Full text of DOI:10.1007/s00044-010-9459-2

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2011) 20:1214–1219
DOI 10.1007/s00044-010-9459-2
ORIGINAL RESEARCH
Synthesis and antimicrobial activity of some
bisoctahydroxanthene-1,8-dione derivatives
•
Muharrem Kaya Erhan Basar Ferdag Colak
•
˘
Received: 12 February 2010 / Accepted: 25 September 2010 / Published online: 13 October 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The bisoctahydroxanthen-1,8-dione derivatives
were synthesized effectively via p-dodecylbenzene sulfonic
acid the catalysed cyclocondensation of cyclic 1,3-dicar-
bonyl compounds with 1,3- or 1,4-benzene dicarboxalde-
hydes in water. The products were obtained with yield
ranged from 75 to 95%. The structures of compounds were
Introduction
Xanthene-based compounds are important because of their
use in medicine as they possess antimicrobial activities
(Krasnoff et al., 1999; Wang et al., 2006; Qiao et al., 1998;
Limsuwan et al., 2009). These compounds have also been
investigated for agricultural bactericidal activity (Krasnoff
et al., 1999), photodynamic therapy, anti-inflammatory
effects (Poupelin et al., 1980) and antiviral activity (Jamison
et al., 1990). In particular, octahydroxanthene constitutes a
structural unit in several natural products (Hatakeyama
et al., 1998) and they are valuable synthons because of the
inherent reactivity of the inbuilt pyran ring (Shchekotikhin
and Nikolaeva, 2006). A number of xanthene-based com-
pounds are also available from natural sources. Santalin
pigments, as they are popularly known, have been isolated
from a number of plant species (Kinjo et al., 1995). The
wide-ranging biological activities associated with xanth-
enes, both naturally occurring and synthetic, ensure that the
synthesis of these compounds remains a topic of current
interest. Many methods are available to synthesize octahy-
droxanthene derivatives (Horning and Horning, 1946; Jin
et al., 2004, 2005, 2006; Odabasoglu et al., 2008). There is a
continuous and urgent need to discover new antimicrobial
compounds with novel mechanisms of action because there
has been an alarming increase in the incidence of new and
re-emerging infectious diseases. Another big concern is the
development of resistance to the antibiotics in current
clinical use (Rojas et al., 2003).
1
characterized by FT-IR, H-NMR and elemental analysis.
The antimicrobial properties of compounds against patho-
gens were investigated by the disc-diffusion method. These
compounds were evaluated for potential antimicrobial
activity against Gram-positive (Staphylococcus aureus,
Bacillus cereus, S. epidermidis and Nocardia canis), Gram-
negative bacteria (Escherichia coli, Proteus vulgaris and
Pseudomonas aeroginosa), yeasts (Candida albicans and
Rhodotorula rubra) and mold (Aspergillus niger). The
growth of S. aureus, B. cereus, S. epidermidis, E. coli,
C. albicans, R. rubra and A. niger were inhibited by 3f and
3g compounds. All compounds were resistant against
Gram-negative bacteria (Proteus vulgaris and Pseudomonas
aerginosa) and results were upon comparison with reference
discs.
Keywords Bisoctahydroxanthen-1,8-diones ꢀ
Antibacterial activity ꢀ Antifungal activity
M. Kaya (&) ꢀ E. Basar
The purpose of this study was to evaluate the potential
antimicrobial activities of the ten compounds. Several
functionalized bisoctahydroxanthenes were prepared from
various ketones and aromatic dialdehydes (Table 1). The
reactions were easily worked up with short time, high
yield and environmental friendliness. The structures of the
Faculty of Science and Arts, Chemistry Department,
Dumlupinar University, 43100 Kutahya, Turkey
e-mail: mhrkaya@yahoo.com
F. Colak
Faculty of Science and Arts, Biology Department,
Dumlupinar University, 43100 Kutahya, Turkey
123

Med Chem Res (2011) 20:1214–1219
1215
Table 1 Effect of the 3a–j compounds on the growth of microorganisms
Test
Microorganisms
Concentrations
(lg/disc)
3a
3b
3c
3d
3e
3f
3 g
3 h
3i
3j
Tetracycline
10 lg/disc
Nystatin
100 U/disc
S. aureus
B. cereus
S. epidermidis
N. canis
20
40
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
7
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
7
7
7
–
–
–
–
–
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
7
8
8
–
–
–
8a
10a
8
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
7
7
–
7
9
–
–
7
–
–
–
–
–
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
9
9
–
–
9
–
–
–
–
–
–
–
–
7
–
–
–
–
–
–
–
7
8
-
–
–
10
15
8
10
14
8
40
28
15
14
25
13
15
140
20
–
–
8a
10a
10a
–
8a
11a
12a
–
40
9
9
140
20
9
8
–
–
40
–
–
8a
10
–
–
140
20
–
–
7
–
–
–
40
–
–
7
–
140
20
–
–
8
–
E.coli
–
–
7
–
40
–
–
8
–
140
20
–
–
9
–
P. aeroginosa
P. vulgaris
C. albicans
R. rubra
–
–
–
–
40
–
–
–
–
–
–
–
–
–
–
7
7
–
–
7
–
–
–
140
20
–
–
–
–
–
–
–
–
40
–
–
–
–
140
20
–
–
–
8a
–
7
8a
7
8a
7
40
9
8
20
21
22
140
20
8
8
9
8
–
–
8a
9a
12
–
8a
9a
10
–
40
–
–
140
20
7
7
A.niger
–
–
40
–
–
–
–
140
–
–
7
7
a
Cloudiness
Zone of inhibition in mm, discs Ø 6 mm
prepared compounds were established from their spectral
(IR, 1H NMR and elemental analyses) data. Synthesis
of octahydroxanthene-1,8-dione is generally achieved by
the condensation of 5,5-dimethyl-1,3-cyclohexanedione
(dimedone) with aldehydes using Lewis acid catalysts. We
have performed the synthesis using the following method
recently reported in the literature by Jin et al. (2004) and
Odabasoglu et al. (2008). We have observed that octahy-
droxanthene-1,8-dione derivatives can easily undergo the
condensation with aromatic dialdehydes in the presence
of p-dodecylbenzene sulfonic acid (DBSA) form 1,3-
diketones (Scheme 1). The mixture of 1,3-cyclohexanedi-
ones 1 and aromatic dialdehydes 2 was refluxed in distilled
water using this heterogeneous catalyst.
Result and discussions
Chemistry
In this study, ten bisoctahydroxanthene derivatives were
prepared by one-pot reaction in distilled water for utilizing
DBSA as a heterogeneous catalyst. The structures of the
synthesized bisoctahydroxanthene derivatives, 3a–j, were
confirmed by IR, 1H NMR spectra and elemental analysis data.
The IR spectra of all of the bisoctahydroxanthenes 3
were showed the sharp peaks for the carbonyl groups in
region between 1666 and 1655 cm-l. The other mmax values
at 3071–3025 cm-1 (aromatic C–H), 2964–2929 cm-1
(aliphatic C–H) were recorded.
123

1216
Med Chem Res (2011) 20:1214–1219
R1
R2
R3
R4
R1
R2
R3
R4
Scheme 1 Synthesis of bis
octahydroxanthene derivatives
3a–j
O
R4
CHO
CHO
O
O
R3
R2
R1
O
O
O
O
4
DBSA
H2O, Reflux
+
R4
R3
R2
R1
R4
R3
R2
R1
O
1
2
3
The 1H NMR spectra of all of the corresponding
against some of the tested Gram-positive, Gram-negative
bacterial strains with the diameters of zone inhibition
ranging between 7 and 15 mm and antifungal activity
against some of the tested yeast and mould strains with the
diameters of zone inhibition ranging between 7 and 12 mm
(Table 1). 3a, 3b and 3h showed antibacterial activity only
against B. cereus. 3f and 3g showed antibacterial activity
against S. aureus, B. cereus, S. epidermidis and E.coli. 3f
and 3g compounds were exhibited high antimicrobial
activity (defined as perfectly clear zone) against S. aureus,
respectively, 15 and 14 mm and yeast isolate (R. Rubra),
respectively, 12 and 10 mm, at the concentration of
140 lg/disc. Furthermore, it appeared that the activity of
the tested compounds increases as the concentration
increases. Five compounds (3a, 3b, 3c, 3d and 3e) did not
show antimicrobial activity against S. aureus, S. epide-
rmidis, N.canis, E. coli, P. aeroginosa and P. vulgaris at
three concentrations. Five compounds (3a, 3b, 3f, 3g and
3h) showed antimicrobial activity (defined as perfectly
clear and cloudiness) against B. cereus with the diameters
of zone inhibition ranging between 7 and 12 mm at three
concentrations. Ten compounds did not show antibacterial
activity against Proteus vulgaris and Pseudomonas aero-
ginosa at three different concentrations. The results were
compounds 3 showed that the tertiary allylic proton (CH)
resonates at relatively low-field singlet
d 4.6 ppm
approximately because this proton is deshielded by the
combined effects of the adjacent double bond and the
aromatic ring. Methyl group protons of compounds 3e, 3f
showed singlet between d 0.84 and 1.36 ppm. Methoxy
group protons of compounds 3c, 3d showed singlet
between d 3.68 and 3.74 ppm. The remaining aliphatic
protons generally appeared as a broad multiple d 3.55 and
1.71 ppm. Signals for the aromatic protons showed in the
range d 6.64–7.74 ppm.
The yield, melting points and reaction time values of
compounds 3a–j are given in Table 2.
Antimicrobial activity
All the compounds have been screened for antimicro-
bial activity by the disc-diffusion method. Antimicro-
bial activity was measured for 40, 80 and 140 lg/disc
concentrations against tested microorganisms (S. aureus,
B. cereus, S. epidermidis, N. canis, E. coli, P. aeroginosa,
P. vulgaris, C. albicans, R.rubra and A. niger) and reported
in Table 1. Ten compounds showed antibacterial activity
Table 2 Preparation of compounds 3a-j promoted by p-dodecylbenzene sulfonic acid in water
Compounds
R1
R2
R3
R4
Aldheyde (2)
Time (h)
Yield (%)
3a
3b
3c
3d
3e
3f
C6H5
H
H
H
1,4-(OHC)C6H4
1,3-(OHC)C6H4
1,4-(OHC)C6H4
1,3-(OHC)C6H4
1,4-(OHC)C6H4
1,3-(OHC)C6H4
1,4-(OHC)C6H4
1,3-(OHC)C6H4
1,4-(OHC)C6H4
1,3-(OHC)C6H4
1
95
92
94
89
92
75
90
92
95
91
C6H5
H
H
H
2
3,4-(Dimethoxy)C6H4
H
H
H
2
3,4-(Dimethoxy)C6H4
H
H
H
2
H
H
CH3
CH3
H
CH3
CH3
H
1
H
H
2.5
1
3g
3h
3i
H
H
H
H
H
H
2
CH3
CH3
CH3
CH3
H
H
1
3j
H
H
1
123

Med Chem Res (2011) 20:1214–1219
1217
compared with reference discs (tetracycline for antibacte-
rial and nystatin for antifungal). The compounds (3a–j) are
more active against Gram-positive than Gram-negative
bacteria, according to the inhibition zone. Gram-negative
bacteria are generally more resistant compared to the
Gram-positive ones. The lack of activity of tested com-
pounds against Gram-negative bacteria could be attributed
to the greater resistance of these bacteria, due to presence
of an extra outer membrane in their cell wall acting as a
barrier foreign for substances including antibiotics (Parekh
and Chanda, 2007). 3f compound showed good antifungal
activity against R. Rubra (12 mm). 3a, 3b, 3c, 3d, 3f, 3g,
3h, 3i and 3j compounds showed weak antifungal activity
against C. albicans at 140 lg concentration. New com-
pounds showed less or no antimicrobial activity against
tested microorganisms when compared with standard
antibiotics.
reaction was monitored by TLC. After completion of the
reactions, the mixture was cooled to room temperature and
solid filtered off and washed with water. The crude products
were purified by recrystallization from ethanol. Compounds
3a–j were prepared similarly from 5-phenylcyclohexane-
1,3-dione, 5-(3,4-dimethoxyphenyl)cyclohexane-1,3-dione,
4,4-dimethylcyclohexane-1,3-dione, cyclohexane-1,3-dione,
dimedone, benzene-1,4-carboxaldehyde and the benzene-
1,3-carboxaldehyde.
9-(4-(1,8-dioxo-3,6-diphenyl-2,3,4,5,6,7,8,9-octahydro-
1H-xanthen-9-yl)phenyl)-2,7-diphenyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3a)
White crystal solid (ethanol); mp 227°C; IR (KBr) m 3060
(aromatic CH), 2938 (aliphatic CH), 1665 (C=O), 1588
;
and 1497 (aromatic C=C), 1180 (CO) cm-1 1H NMR
The antimicrobial activities of some xanthenes have
been reported previously (Krasnoff et al., 1999; Wang
et al., 2006; Qiao et al., 1998; Limsuwan et al., 2009).
However, up to the present, no systematic study has been
undertaken to examine the antimicrobial properties of
octahydroxanthen-1,8-dione dyes. For this reason, in the
present investigation, different microorganisms have been
chosen and the antimicrobial effect of bisoctahydroxan-
then-1,8-diones dyes on these microorganisms under in
vitro conditions has been studied.
(400 MHz, CDCl3) d 2.33–2.34 (m, 4H, 49 CH),
2.66–2.81 (m, 6H, 39 CH2), 2.85–2.99 (m, 6H, 39 CH2),
3.05–3.11 (m, 2H, CH2), 3.50–3.55 (m, 2H, CH2), 4.68
(s, 2H, 29 CH), 7.08 (s, 1H, ArH), 7.11–7.14 (m, 1H,
ArH), 7.19–7.29 (m, 11H, ArH), 7.32–7.36 (m, 6H, ArH),
7.39–7.41 (m, 5H, ArH); C56H46O6 requires: C, 82.53; H,
5.69; found: C, 82.48; H, 5.61.
9-(3-(1,8-dioxo-3,6-diphenyl-2,3,4,5,6,7,8,9-octahydro-
1H-xanthen-9-yl)phenyl)-2,7-diphenyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3b)
Experimental
White crystal solid (ethanol); mp 249–251°C; IR (KBr) m
3031 (aromatic CH), 2950 (aliphatic CH), 1660 (C=O),
1586 and 1496 (aromatic C=C), 1180 (CO) cm-1; 1H NMR
(400 MHz, CDCl3) d 2.33–2.34 (m, 4H, 49 CH),
2.64–2.76 (m, 6H, 39 CH2), 2.86–3.02 (m, 6H, 39 CH2),
3.05–3.18 (m, 2H, CH2), 3.51–3.54 (m, 2H, CH2), 4.70 and
4.73 (29 s, 2H, 29 CH), 7.19–7.29 (m, 12H, ArH),
7.31–7.41 (m, 7H, ArH), 7.43–7.49 (m, 2H, ArH),
7.62–7.74 (m, 3H, ArH); C56H46O6 requires: C, 82.53; H,
5.69; found C, 82.44; H, 5.60.
Chemistry
The chemicals used in the synthesis of all the ketones and
aromatic dialdheydes were obtained from Aldrich Chemi-
cal Company. All chemicals and solvents used for the
synthesis were spectroscopic reagent grade. Melting points
were measured on a Bibby Stuart Scientific apparatus.
FT-IR spectra were recorded from a Bruker Optics Vertex
70 ATR-FTIR spectrometer. 1H NMR spectra were
obtained with a Bruker DPX-400 FT-NMR instrument with
deuterated chloroform (CDCl3) and dimethyl sulfoxide
(DMSO-d6) as solvent with tetramethylsilane as the refer-
ence standard. Chemical shifts are expressed in d units
(ppm). The elemental analyses (C, H and N) were recorded
on an Elemental Analyzer LECO CHNS-932.
9-(4-(3,6-bis(3,4-dimethoxyphenyl)-1,8-dioxo-
2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl)-2,7-
bis(3,4-dimethoxyphenyl)-3,4,5,6,7,9-hexahydro-1H-
xanthene-1,8-(2H)-dione (3c)
White crystal solid (ethanol); mp 253°C (dec.); IR (KBr) m
3047 (aromatic CH), 2939 (aliphatic CH), 1664 (C=O),
1591 and 1518 (aromatic C=C), 1187 (CO) cm-1; 1H NMR
(400 MHz, CDCl3) d 2.33–2.34 (m, 4H, 49 CH),
2.68–2.76 (m, 6H, 39 CH2), 2.81–2.84 (m, 2H, CH2),
2.88–2.90 (m, 2H, CH2), 2.94–3.12 (m, 4H, 29 CH2),
3.41–3.46 (m, 2H, CH2), 3.68 and 3.71 (29 s, 24H,
8xOCH3), 4.69 (s, 2H, 29 CH), 6.64–6.79 (m, 3H, ArH),
Typical procedure for preparation
of bisoctahydroxanthene-1,8-diones (3a–j)
A mixture of a cyclohexane-1,3-dione 1 (4.0 mmol), aro-
matic dialdehyde 2 (1.0 mmol) and DBSA (0.42 g) in water
(40 ml) was stirred at refluxing for 1 h. The progress of the
123

1218
Med Chem Res (2011) 20:1214–1219
9,90-(1,3-phenylene)bis(3,4,6,7-tetrahydro-2H-xanthene-
1,8-(5H,9H)-dione) (3h)
6.80–6.88 (m, 6H, ArH), 6.95–7.05 (m, 5H, ArH),
7.08–7.17 (m, 1H, ArH), 7.21–7.25 (m, 1H, ArH);
C64H62O14 requires: C, 72.85; H, 5.92; found C, 72.77; H,
5.89.
White crystal solid (ethanol); mp 212°C (dec.). IR (KBr) m
3025 (aromatic CH), 2953 (aliphatic CH), 1654 (C=O),
1590 (aromatic C=C), 1176 (CO) cm-1
;
1H NMR
9-(3-(3,6–bis(3,4-dimethoxyphenyl)-1,8-dioxo-
2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-Yl)phenyl)-2,7-
bis(3,4-dimethoxyphenyl)-3,4,5,6,7,9-hexahydro-1H-
xanthene-1,8-(2H)-dione (3d)
(400 MHz, CDCl3) d 1.79–1.90 (m, 4H, 29 CH2),
1.94–2.02 (m, 4H, 29 CH2), 2.21–2.36 (m, 8H, 49 CH2),
2.58–2.74 (m, 8H, 49 CH2), 4.53 and 4.66 (29 s, 2H, CH),
6.93–6.96 (m, 2H, ArH), 7.00–7.05 (t, 1H, ArH), 7.45–7.69
(m, 1H, ArH); C32H30O6 requires: C, 75.28; H, 5.92; found
C, 75.20; H, 5.88.
Yellow solid (ethanol); mp 293°C (dec.); IR (KBr) m 3071
(aromatic CH), 2936 (aliphatic CH), 1666 (C=O), 1591
;
and 1516 (aromatic C=C), 1183 (CO) cm-1 1H NMR
9,90-(1,4-phenylene)bis(3,3,6,6-tetramethyl-3,4,6,7-
tetrahydro-2H-xanthene-1,8-(5H,9H)-dione) (3i)
(400 MHz, CDCl3) d 2.33–2.34 (m, 4H, 49 CH),
2.67–2.77 (m, 8H, 49 CH2), 2.84–2.98 (m, 6H, 39 CH2),
3.16–3.20 (m, 2H, CH2), 3.73 and 3.74 (29 s, 24H, 89
OCH3), 4.65 and 4.67 (29 s, 2H, 29 CH), 6.75–6.77
(m, 2H, ArH), 6.84–6.89 (m, 6H, ArH), 6.99–7.07 (m, 5H,
ArH), 7.11–7.17 (m, 2H, ArH), 7.21 (s, 1H, ArH);
C64H62O14 requires: C, 72.85; H, 5.92; found C, 72.72; H,
5.86.
mp 273–275°C (dec.), 274–275 (Tu et al., 2004; Cagulada
et al., 2009).
9,90-(1,3-phenylene)bis(3,3,6,6-tetramethyl-3,4,6,7-
tetrahydro-2H-xanthene-1,8-(5H,9H)-dione) (3j)
mp 253–254°C (dec.), 252–253 (Tu et al., 2004).
9,90-(1,4-phenylene)bis(2,2,7,7-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione) (3e)
Antimicrobial activity
White crystal solid (ethanol); mp 269°C (dec.). IR (KBr) m
3049 (aromatic CH), 2964 (aliphatic CH), 1655 (C=O),
1578 and 1508 (aromatic C=C), 1183 (CO) cm-1; 1H NMR
(400 MHz, CDCl3) d 0.86 (s, 12H, 49 CH3), 0.99 (s, 12H,
49 CH3), 1.71–1.85 (m, 8H, 49 CH2), 2.59–2.78 (m, 8H,
49 CH2), 4.61 (s, 2H, 29 CH), 7.42 (s, 4H, ArH);
C40H46O6 requires: C, 77.14; H, 7.44; found C, 77.04;
H, 7.40.
Test microorganisms
The antimicrobial activity of the synthesized compounds
was evaluated against Gram-positive (B. cereus NRRL
3711, Staphylococcus aureus ATCC 25923, S. epidermidis
ATCC 12228, Nocardia canis) and Gram-negative (Esche-
richia coli ATCC 25922, Proteus vulgaris NRRL-B-123,
Pseudomonas aeroginosa ATCC 27853) bacterial strains,
yeast cultures (Candida albicans ATCC 10231, Rhodotor-
ula rubra) and mould culture (Aspergillus niger ATCC
10949). Bacterial and fungal cultures of test organisms were
maintained on Nutrient agar slants at 4°C and were sub-
cultured in petri dishes prior to use. Ten compounds were
tested for their antimicrobial (antibacterial and antifungal)
activities by disc-diffusion method (NCCLS, 1997) using
Nutrient Agar medium for bacteria and fungi. The com-
pounds were dissolved in DMSO. Antimicrobial activity
was measured for three concentrations (40, 80 and 140 lg
for each disc). Disc containing DMSO was used as control.
Test bacteria were transferred to tubes containing 4 to 5 ml
Nutrient Broth. The test cultures were incubated at 37°C
until they were visibly turbid. The density of these cultures
was adjusted to 0.5 Mc Farland (at 625 nm, 0.08–0.1
absorbance) with sterile saline. After autoclaving, Nutrient
Agar was poured into petri dishes to give a uniform depth of
approximately 4 mm and was allowed to a cool temperature.
9,90-(1,3-phenylene)bis(2,2,7,7-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione) (3f)
Yellow solid (ethanol); mp 131°C (dec.). IR (KBr) m 3032
(aromatic CH), 2929 (aliphatic CH), 1665 (C=O), 1581 and
1514 (aromatic C=C), 1149 (CO) cm-1
;
1H NMR
(400 MHz, CDCl3) d 0.84, 0.98, 1.27 and 1.36 (49 s, 24H,
89 CH3), 1.71–1.86 (m, 8H, 49 CH2), 2.22–2.65 (m, 8H,
49 CH2), 4.47 and 4.52 (29 s, 2H, 29 CH), 6.79 (t, 1H,
ArH), 6.90–7.05 (m, 3H, ArH); C40H46O6 requires: C,
77.14; H, 7.44; found C, 77.10; H, 7.38.
9,90-(1,4-phenylene)bis(3,4,6,7-tetrahydro-2H-xanthene-
1,8-(5H,9H)-dione) (3g)
Yellow solid (ethanol); mp °C (dec.) [300, 338–340
(Cremlyn and Shabbir, 2004).
123

Med Chem Res (2011) 20:1214–1219
1219
A suspension containing approximately 108 CFU/ml for
bacteria, 107 CFU/ml for yeasts and 105 CFU/ml for mould
was spread on the plates of Nutrient Agar. The entire surface
of the Nutrient Agar plates were inoculated by streaking with
a sterile swab dipped into adjusted suspension. Then, the
paper discs impregnated with the solutions of the compounds
tested were placed on the surface of the media inoculated
with the microorganisms. The plates were incubated at 37°C
for 24 h for bacterial strains, 48 h for yeast and at room
temperature for 72 h for fungi, after pre-incubation for 1 h at
4°C. After incubation, the growth inhibition zone around the
disc were observed indicating that the examined compounds
inhibits the growth of microorganisms. Each assay in this
experiment was repeated three times. Tetracycline (10 lg/ml)
for bacteria and Nystatin (100 U) for yeast and fungi were
used as positive control.
Jamison JM, Krabill K, Hatwalkar A, Jamison E, Tsai C (1990)
Potentiation of the antiviral activity of poly r(a-u) by xanthene
dyes. Cell Biol Int Rep 14(12):1075–1084
Jin TS, Zhang JS, Xiao JC, Wang AQ, Li TS (2004) Clean synthesis
of 1,8-dioxo-octahydroxanthene derivatives catalyzed by
p-dodecylbenezenesulfonic acid in aqueous media. Synlett
(5):866–870
Jin TS, Zhang JS, Xiao JC, Wang AQ, Li TS (2005) Solid-state
condensation reactions between aldehydes and 5,5-dimethyl-1,
3-cyclohexanedione by grinding at room temperature. Synth
Commun 35(17):2339–2345
Jin TS, Zhang JS, Xiao JC, Wang AQ, Li TS (2006) The reaction of
aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione
under solvent-free grinding conditions. Indian J Chem
45(2):470–474
B
Kinjo J, Uemura H, Nohara T, Yamashita M, Marubayashi N,
Yoshihira K (1995) Novel yellow pigment from Pterocarpus
santalinus: biogenetic hypothesis for santalin analogs. Tetrahe-
dron Lett 36(31):5599–5602
Krasnoff SB, Faloon D, Williams JE, Gibson DM (1999) Toxicity of
xanthene dyes to Entomopathogenic fungi. Biocontrol Sci Techn
9(2):215–225
Limsuwan S, Trip EN, Kouwen TRHM, Piersma S, Hiranrat A,
Mahabusarakam W, Voravuthikunchai SP, van Dijl JM, Kayser
O (2009) Rhodomyrtone: a new candidate as natural antibacte-
rial drug from Rhodomyrtus tomentosa. Phytomedicine 16(6–7):
645–651
NCCLS (National Committee for Clinical Laboratory Standards)
(1997) Performance standards for antimicrobial disk suscepti-
bility test, 6th edn. Wayne PA: Approved Standard. M2-A6
Conclusions
In conclusion, novelty bisoctahydroxanthene derivatives
were synthesized with higher yields. Afterwards, the anti-
microbial activities of all synthesized compounds were
determined by disc-diffusion method. In general, tested
compounds showed antimicrobial activity against S. aureus,
B. cereus, C. albicans and R.rubra. 3f and 3g compounds
showed antimicrobial activity tested microorganisms except
P. aeroginosa and P. vulgaris at tested concentration
(140 lg/disc). The present study adds new data in the rela-
tionships of xanthenes and their antimicrobial activities.
¨
Odabasoglu M, Kaya M, Yıldırır Y, Bu¨yu¨kgu¨ngor O (2008) 9-(4-
Methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-
xanthene-1,8(5H,9H)-dione. Acta Cryst E 64:o681
Parekh J, Chanda S (2007) In vitro antibacterial activity of the crude
methanol extract of Woodfordia fruticosa kurz. flower (Lythr-
aceae). Braz J Microbiol. 38(2):204–207
Poupelin JP, Saintruf G, Perche JC, Roussey JC, Laude B, Narcisse G,
Bakrilogeais F, Hubert F (1980) 2-Hydroxy-1,3 indandione
derivatives: condensation of ninhydrine with polyphenois and
their o-methylated derivatives. Eur J Med Chem 15(3):253–262
Qiao YF, Okazaki T, Ando T, Mizoue K, Kondo K, Eguchi T,
Kakinuma K (1998) Isolation and characterization of a new
pyrano[40,30:6,7]naphtho[1,2-b]xanthene antibiotic FD-594.
J Antibiot 51(3):282–287
Acknowledgment The authors are very grateful to Dumlupinar
University Research Fund for providing financial support for this
project (Grant No. 2008-4).
Rojas R, Bustamante B, Bauer J, Fernandez I, Alban J, Lock O (2003)
Antimicrobial activity of selected Peruvian medicinal plants.
J Ethnopharmacol 88(2–3):199–204
References
Cagulada AM, Lynch DE, Hamilton DG (2009) Structure and
properties of modular components for applications in topological
supramolecular chemistry. Cryst Growth Des 9(2):825–832
Cremlyn RJ, Shabbir G (2004) Chlorosulfonation of 9-aryloctahy-
droxanthen-1,8-diones. Phosphorus Sulfur Silicon 179(12):
2635–2643
Hatakeyama S, Ochi N, Numata H, Takano S (1998) A new route to
substituted 3-methoxycarbonyldihydropyrans—enantioselective
synthesis of (-)-methyl elenolate. Chem Commun 17:1202–1204
Horning EC, Horning MG (1946) Methone derivatives of aldehydes.
J Org Chem 11:95
Shchekotikhin YM, Nikolaeva TG (2006) Transformations of sym-
octahydroxanthene-1,8-diones and salts of 1,8-dioxo-sym-octa-
hydroxanthylium in the recyclization reactions under the action
of amines. Chem Heterocycl Compd 1:32–38
Tu S, Gao Y, Miao C, Zhu S, Li T, Zhang X, Shi D (2004) The
reaction of aromatic dialdehyde with dimedone under micro-
wave irradiation. Synth Commun 34(14):2617–2622
Wang H, Lu L, Zhu S, Li Y, Cai W (2006) The phototoxicity of
xanthene derivatives against Escherichia coli, Staphylococcus
aureus, and Saccharomyces cerevisiae. Curr Microbiol 52(1):
1–5
123