Indium(III) chloride catalyzed three-component coupling reaction: A novel synthesis of 2-substituted aryl(indolyl)kojic acid derivatives as potent antifungal and antibacterial agents

Article abstract of DOI:10.1016/j.bmcl.2010.10.003

Three-component coupling of aldehyde, indole and kojic acid has been achieved using a catalytic amount of InCl₃ under solvent free conditions to produce a novel series of 2-substituted aryl(indolyl)kojic acid derivatives in good yields and with

Full text of DOI:10.1016/j.bmcl.2010.10.003

Bioorganic & Medicinal Chemistry Letters 20 (2010) 7507–7511
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Indium(III) chloride catalyzed three-component coupling reaction: A novel
synthesis of 2-substituted aryl(indolyl)kojic acid derivatives as potent
antifungal and antibacterial agents
B. V. Subba Reddy a, , M. Ramana Reddy a, Ch. Madan a, K. Pranay Kumar b, M. Srinivasa Rao b
⇑
a Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Three-component coupling of aldehyde, indole and kojic acid has been achieved using a catalytic amount
of InCl3 under solvent free conditions to produce a novel series of 2-substituted aryl(indolyl)kojic acid
derivatives in good yields and with high selectivity. These compounds are found to exhibit potent anti-
fungal properties.
Received 20 May 2010
Revised 29 September 2010
Accepted 1 October 2010
Available online 14 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Kojic acid
Indole
Aldehyde
Indium(III) halide
Antifungal and antibacterial activity
Multi-component, one-pot syntheses have received consider-
able attention because of their wide range of applications in phar-
maceutical chemistry for generation of structural diversity and
combinatorial libraries for drug discovery.1 The indole nucleus is
an important structural motif in medicinal chemistry.2–4 Substi-
tuted indoles have been referred to as privileged structures as they
are capable of binding to many receptors with high affinity.5–8
Therefore, the synthesis and selective functionalization of indoles
have been the focus of active research over the years.9–16 Recently,
InCl3 has emerged as a mild Lewis acid catalyst for a variety of or-
ganic transformations.17–24 However, to the best of our knowledge,
there are no reports on the coupling of indole, aldehyde and kojic
acid by means of a three-component reaction to produce a novel
class of 2-substituted aryl(indolyl)kojic acid derivatives.
Following our interest on catalytic application of indium(III)
chloride,25–29 we herein disclose a novel three-component reaction
for the one-pot synthesis of 2-substituted aryl(indolyl)kojic acid
derivatives from kojic acid, aryl aldehydes and indoles. Thus treat-
ment of benzaldehyde with indole and kojic acid in presence of
10 mol % of InCl3 at 120 °C under solvent free conditions gave
5-bromo, 5-chloro derivatives. Aromatic aldehydes such as p-
methoxy, m-phenoxy, o-chloro, 2,4,6-trimethylbenzaldehydes
and 2-naphthaldehyde reacted well with kojic acid to afford
2-substituted aryl(indolyl)kojic acid derivatives in good yields
(Table 1). Aliphatic aldehyde, for example, n-propanaldehyde also
participated well in this reaction under similar conditions (entry
l, Table 1). Both aromatic aldehydes and aliphatic aldehyde worked
well in this reaction. Interestingly, bromo and chloro substituted
indoles were also effective for this three-component reaction
(entries i and j, Table 1). In the absence of InCl3, the products were
obtained in low yield (20–35%) after long reaction times (8–12 h).
Mechanistically, we assume that the reaction proceeds via the for-
mation of enone from kojic acid and aldehyde. The resulting enone
may undergo conjugate addition with indole to give the desired
product as depicted in Scheme 2.
CHO
the
2-((1H-indol-3-yl)(phenyl)methyl)-3-hydroxy-6-(hydroxy-
O
O
InCl3
O
O
OH
methyl)-4H-pyran-4-one 4a in 85% yield (Scheme 1).
This result provided the incentive for further study of reactions
with various substituted indoles such as 2-methyl, 2-phenyl,
OH
+
º
120 C
HO
N
H
N
H
HO
4a
⇑
Corresponding author. Tel.: +91 40 7160512.
E-mail address: basireddy@iict.res.in (B.V.S. Reddy).
Scheme 1. 3CC reaction of indole, benzaldehyde and kojic acid.
0960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.10.003

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B. V. Subba Reddy et al. / Bioorg. Med. Chem. Lett. 20 (2010) 7507–7511
Table 1
InCl3-catalyzed one-pot synthesis of 2-substituted alkyl and aryl(indolyl)kojic acid derivatives
Entry
a
Indole (1)
Aldehyde (2)
Koijc acid (3)
Product (4)a
Time (min)
65
Yieldb (%)
85
CHO
O
Ar
HO
O
N
H
HO
OH
O
N
H
OH
O
CHO
O
Ar
HO
O
N
H
HO
OH
O
b
c
d
e
f
70
55
60
55
75
75
65
75
75
85
80
75
80
87
85
85
80
80
85
90
90
75
80
85
N
H
OH
O
OMe
CHO
O
Ar
HO
O
N
H
HO
OH
O
OPh
N
H
OH
O
CHO
O
Ar
HO
O
N
H
HO
OH
O
N
H
OH
O
OMe
CHO
O
Ar
HO
O
N
H
HO
OH
O
OPh
N
H
OH
O
CHO
O
Ar
HO
O
N
H
HO
OH
O
OMe
OH
N
H
OH
O
CHO
O
Ar
HO
O
N
H
HO
OH
O
g
h
i
N
H
OH
O
Cl
CHO
O
Ar
HO
O
N
H
HO
OH
O
N
H
OH
O
Br
CHO
O
Ar
HO
Br
Cl
O
HO
N
H
OH
O
N
H
OH
O
OMe
CHO
Cl
O
Ar
HO
O
HO
N
H
OH
O
j
N
H
OH
O
OMe
CHO
O
Ar
HO
Ph
O
N
H
HO
OH
O
k
l
Ph
N
H
OH
O
OMe
CHO
O
HO
Ph
O
N
H
HO
OH
O
Ph
N
H
OH
O
CHO
OH
O
Ar
HO
Ph
O
N
H
HO
OH
O
m
Ph
N
H
OH
O
a
All products were characterized by 1H NMR, IR and mass spectroscopy.
Yield refers to pure products after chromatography.
b
R
O
InCl3
R
H
O
O
O
O
HO
R
H
H
HO
+
O
O
O
N
H
HO
O
O
InCl3
-H2O
InCl3
OH
..
R
O
O
HO
N
OH
H
Scheme 2. A plausible reaction mechanism.
The scope and generality of this process is illustrated with re-
The minimum inhibitory concentrations (MIC) of various syn-
thetic compounds were tested against three representative Gram
positive organisms viz. Bacillus subtilis (MTCC 441), Staphylococcus
spect to various indoles and aldehydes and the results are pre-
sented in Table 1.30

B. V. Subba Reddy et al. / Bioorg. Med. Chem. Lett. 20 (2010) 7507–7511
7509
Table 2
Antibacterial activity of compounds 4d–4l
MIC (lg/mL)
Compd code
B. Subtilis
S. aureus
S. epidermidis
E. coli
P. aeruginosa
K. pneumoniae
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
150
150
150
150
150
150
150
150
150
150
150
18.75
150
1.562
6.25
150
150
150
150
75
150
75
150
18.75
150
37.5
4.68
75
9.375
37.5
12.5
6.25
150
75
75
150
75
150
18.75
150
37.5
4.68
75
37.5
18.75
12.5
1.562
75
75
75
150
75
150
75
150
75
18.75
150
75
37.5
37.5
150
18.75
150
18.75
18.75
150
150
150
18.75
150
18.75
150
150
18.75
150
37.5
150
18.75
2.34
37.5
9.375
4.68
1.562
6.25
4m
Penicillin
Streptomycin
75
6.25
3.125
3.125
3.125
Table 3
Antifungal activity of compounds 4d–4l
Zone of Inhibition (mm)
Compound code
R. oryzae
A. niger
C. rugosa
150
C. albicans
S. cerevisiae
100
l
g
150
l
g
100
l
g
150
lg
100
lg
lg
100
l
g
150
lg
100
l
g
150 lg
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
0
0
7
0
0
0
7
0
0
0
0
0
0
0
0
10
0
0
0
10
0
0
0
0
10
0
11
0
9
0
8
0
12
14
10
0
14
0
16
0
14
0
12
0
18
20
14
0
6
6
13
0
11
0
0
0
13
0
10
0
0
9
9
18
0
16
0
0
0
19
0
14
0
0
0
0
14
0
9
0
0
0
13
11
9
0
0
19
0
14
0
0
0
0
14
0
10
0
0
0
0
19
0
14
0
0
0
0
0
18
16
12
0
10
16
9
14
12
22
16
21
14
20
16
0
0
0
10
23.5
4m
0
25
0
14
Ampotericin B
24
22
aureus (MTCC 96), Staphylococcus epidermidis (MTCC 2639) and
Gram-negative organisms viz Escherichia coli (MTCC 443), Pseudo-
monas aeruginosa (MTCC 741), and Klebsiella pneumoniae (MTCC
618) by broth dilution method recommended by National Commit-
tee for Clinical Laboratory (NCCL) standards (1).31 Standard Anti-
bacterial agents like Penicillin and Streptomycin were also
screened under identical conditions for comparison. The minimum
inhibitory concentration (MIC) values are presented in Table 2.
The minimum inhibitory concentration (MIC) was determined
for each compound against with Penicillin and Streptomycin as
standard controls and the results are presented in Table 2. The
MIC values of indolyl kojic acid derivatives against tested organ-
isms displayed significant activity with a high degree of variation.
Only compound 4l showed substantial activity against all the
tested organisms. Moderate activity was shown by the compounds
4g, 4j, 4m and 4i against all the tested organisms except for
B. subtilis. Among them, 4j was more effective especially against
S. aureus, E. coli and P. aeruginosa. Compounds 4b and 4c were
showed similar activity against all tested strains. The compounds
4d, 4h, 4f and 4a have not been shown any notable activity com-
pared to other compounds and 4e, 4k showed some activity
against S. aureus.
Agar Well Diffusion Method (2). The ready-made Potato Dextrose
Agar (PDA) medium (Hi-media, 39 g) was suspended in distilled
water (1000 mL) and heated to boiling until it dissolved com-
pletely, the medium and Petri dishes were autoclaved at pressure
of 15 lb/inc32 for 20 min. Agar well bioassay was employed for test-
ing antifungal activity in Table 3.
The medium was poured into sterile Petri dishes under aseptic
conditions in a laminar air flow chamber. When the medium in the
plates solidified, 0.5 mL of (week old) culture of test organism was
inoculated and uniformly spread over the agar surface with a ster-
ile L-shaped rod. Solutions were prepared by dissolving the com-
pound in DMSO and different concentrations were made. After
inoculation, wells were scooped out with 6 mm sterile cork borer
and the lids of the dishes were replaced. To each well different con-
centrations of test solutions were added. Controls were main-
tained. The treated and the controls were kept at 27 °C for 48 h.
Inhibition zones were measured and the diameter was calculated
in millimeter. Three to four replicates were maintained for each
treatment.
The antifungal screening data of 4a–4m revealed that all the
tested compounds showed moderate to good antifungal activities
against the tested fungal strains. The compounds 4b, 4d, 4h, 4b,
4f are showing no activity against the tested organisms. The com-
pound 4c showed better antifungal activity against all fungal
strains. The compounds 4e, 4j, 4i and 4k displayed antifungal
activity except on R. oryzae. Compound 4e and 4k exhibited almost
In vitro antifungal activity of the newly synthesized compounds
was studied against the fungal strains, Candida albicans (MTCC
227), Candida rugosa (NCIM 3462), Saccharomyces cerevisiae (MTCC
36), Rhizopus oryzae (MTCC 262), Aspergillus niger (MTCC 282) by

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B. V. Subba Reddy et al. / Bioorg. Med. Chem. Lett. 20 (2010) 7507–7511
pyran-4-one (4b): solid, mp 97–99 °C; 1H NMR (300 MHz, DMSO + CDCl3, 1:4):
d 10.21 (s, 1H), 7.47 (s, 1H), 6.72–7.35 (m, 9H), 6.38 (s, 1H), 5.95 (s, 1H), 4.27 (s,
2H), 3.75 (s, 3H); 13C NMR (75 MHz, DMSO): d 173.2, 167.0, 157.9, 151.3, 140.6,
similar activity. The compounds 4j and 4c were observed as most
active with a zone of inhibition values in the range of 11–21 mm
at the concentration of 150 lg/mL. Narrow spectrum of activity
was observed with 4m against C. albicans and S. cerevisiae and 4l
136.1, 132.3, 129.2, 126.3, 123.8, 121.1, 118.5, 118.4, 111.5, 108.9; IR (KBr):
m
3288, 2929, 1652, 1618, 1580, 1511, 1456, 1309, 1255, 1095, 998, 765,
738 cmÀ1; ESI-MS: m/z [M+1] 378.
against S. cerevisiae.
2-((1H-Indol-3-yl)(3-phenoxyphenyl)methyl)-3-hydroxy-6-(hydroxymethyl)-4H-
pyran-4-one (4c): solid, mp 94–95 °C; 1H NMR (500 MHz, DMSO + CDCl3, 1:4): d
10.35 (s, 1H), 7.99 (s, 1H), 6.80–7.34 (m, 14H), 6.37 (s, 1H), 6.02 (s, 1H), 5.30 (s,
1H), 4.25 (s, 2H); 13C NMR (75 MHz, DMSO): d 173.7, 167.2, 156.6, 156.4, 150.6,
142.6, 141.0, 136.1, 129.9, 126.2, 124.0, 123.4, 121.3, 118.7, 118.5, 116.8, 112.4,
In summary, we have developed a novel method for the synthe-
sis of 2-substituted aryl(indolyl)kojic acid derivatives by means of
a three-component reaction between kojic acid, aldehyde and in-
dole using a catalytic amount of InCl3 under neat conditions. This
method is simple and convenient to prepare a wide range of kojic
acid derivatives in a single-step operation which are found to pos-
sess interesting antibacterial and antifungal properties.
111.6, 108.9, 59.5, 48.5, 30.1, 29.0, 17.2; IR (KBr):
m 3408, 2923, 1621, 1581,
1484, 1451, 1235, 1008, 746 cmÀ1; ESI-MS: m/z [M+1] 440.
3-Hydroxy-6-(hydroxymethyl)-2-((4-methoxy-phenyl)(2-methyl-1H-indol-3-
yl)methyl)-4H-pyran-4-one (4d): solid, mp 90–92 °C; 1H NMR (500 MHz,
DMSO + CDCl3, 1:4): d 10.42 (s, 1H), 8.13 (s, 1H), 6.72–7.20 (m, 8H), 6.36 (s,
1H), 6.04 (s, 1H), 5.25 (s, 1H), 4.10–4.27 (m, 2H), 3.74 (s, 3H), 2.37 (s, 3H); 13C
NMR (75 MHz, DMSO): d 173.6, 170.4, 167.1, 157.6, 151.5, 141.3, 135.2, 133.4,
131.7, 128.7, 127.4, 120.0, 118.9, 113.6, 110.5, 108.8, 59.7, 59.4, 54.9, 20.7,
Acknowledgement
14.07, 11.8; IR (KBr):
m 3391, 2924, 1713, 1618, 1576, 1509, 1456, 1302, 1245,
1179, 1030, 860, 828, 745 cmÀ1; ESI-MS: m/z [M+1] 392.
MRR thanks CSIR, New Delhi for the award of a fellowship.
References and notes
3-Hydroxy-6-(hydroxymethyl)-2-((2-methyl-1H-indol-3-yl)(3-
phenoxyphenyl)methyl)-4H-pyran-4-one (4e): solid, mp 85–87 °C; 1H NMR
(500 MHz, DMSO + CDCl3, 1:4): d 10.55 (s, 1H), 8.35 (s, 1H), 7.20–7.25 (m,
5H), 6.78–7.02 (m, 8H), 6.33 (s, 1H), 6.06 (s, 1H), 5.31 (s, 1H), 4.09–4.26 (m,
2H), 2.37 (s, 3H); 13C NMR (75 MHz, DMSO): d 173.5, 167.1, 156.4, 156.4, 150.6,
142.1, 141.4, 135.1, 133.6, 129.8, 127.2, 122.8, 123.2, 120.0, 118.8, 118.3, 118.2,
1. Zhu, J.; Bienayme, H. Multi-Component Reactions; Wiley: Weinheim, 2005.
2. Sundberg, R. J. Indoles; Academic Press, 1996.
3. Faulkner, D. J. Nat. Prod. Rep. 2001, 18, 1.
118.1, 116.6, 110.5, 108.5, 108.7, 107.8, 59.3, 11.7; IR (KBr): m 3393, 2924, 2854,
1620, 1580, 4184, 1455, 1238, 1161, 1081, 746 cmÀ1; ESI-MS: m/z [M+1] 454.
3-Hydroxy-2-((4-hydroxy-3-methoxyphenyl) (2-methyl-1H-indol-3-yl)methyl)-6-
(hydroxymethyl)-4H-pyran-4-one (4f): solid, mp 80–82 °C; 1H NMR (300 MHz,
DMSO + CDCl3, 1:4): d 10.41 (s, 1H), 8.13 (s, 1H), 6.55–7.29 (m, 7H), 6.33 (s, 1H),
5.97 (s, 1H), 5.10 (s, 1H), 4.14–4.27 (m, 2H), 3.65 (s, 3H), 2.35 (s, 3H); 13C NMR
(75 MHz, DMSO): d 173.6, 168.1, 167.0, 151.1, 147.4, 145.0, 141.1, 139.2,
138.16, 133.4, 130.6, 127.5, 120.2, 118.9, 118.3, 115.2, 112.3, 110.5, 109.8,
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Abhilash, K. G. Tetrahedron Lett. 2006, 47, 2871.
108.9, 59.5, 55.6, 11.8; IR (KBr):
m 3388, 2952, 2855, 1651, 1617, 1573, 1512,
1456, 1198, 1029, 859, 744 cmÀ1; ESI-MS: m/z [M+1] 408.
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2-((4-Chlorophenyl)(2-methyl-1H-indol-3-yl)
methyl)-3-hydroxy-6-
(hydroxymethyl)-4H-pyran-4-one (4g): solid, mp 92–94 °C; 1H NMR (500 MHz,
DMSO + CDCl3, 1:4): d 10.64 (s, 1H), 8.45 (s, 1H), 7.12–7.25 (m, 6H), 6.94 (t, 1H,
J = 7.3 Hz), 6.82 (t, 1H, J = 7.3 Hz), 6.33 (s, 1H), 6.03 (s, 1H), 5.33 (s, 1H), 4.09–
4.25 (m, 2H), 2.39 (s, 3H); 13C NMR (75 MHz, DMSO): d 173.5, 167.1, 150.4,
141.4, 138.8, 135.2, 133.7, 130.9, 129.5, 128.1, 127.1, 120.1, 118.7, 118.4, 110.5,
108.8, 107.7, 59.3, 38.2, 11.7; IR (KBr):
m 3391, 2922, 1650, 1621, 1576, 1457,
1304, 1201, 1089, 1013, 860, 821, 747 cmÀ1; ESI-MS: m/z [M+1] 396.
3-Hydroxy-6-(hydroxymethyl)-2-((2-methyl-1H-indol-3-yl)(naphthalen-2-
yl)methyl)-4H-pyran-4-one (4h): solid, mp 87–89 °C; 1H NMR (500 MHz,
DMSO + CDCl3, 1:4):
d 10.19 (s, 1H), 7.24–7.74 (m, 9H), 6.95 (t, 1H,
J = 7.3 Hz), 6.82 (t, 1H, J = 7.3 Hz), 6.42 (s, 1H), 6.23 (s, 1H), 5.07 (s, 1H),
4.13–4.27 (m, 2H), 2.42 (s, 3H); 13C NMR (75 MHz, DMSO): d 173.6, 167.2,
150.9, 141.5, 137.6, 135.6, 135.1, 133.7, 132.8, 131.6, 127.4, 127.7, 126.5, 126.0,
125.5, 125.5, 120.0, 118.7, 118.3, 110.5, 108.8, 108.1, 59.4, 59.7, 20.6, 11.8,
14.0; IR (KBr):
m 3484, 3265, 2908, 1713, 1626, 1583, 1457, 1372, 1244, 1194,
1159, 1159, 1094, 983, 858, 827, 751 cmÀ1; ESI-MS: m/z [M+1] 412.
2-((5-Bromo-1H-indol-3-yl)(4-methoxyphenyl)
methyl)-3-hydroxy-6-
(hydroxymethyl)-4H-pyran-4-one (4i): viscous liquid; 1H NMR (300 MHz,
DMSO + CDCl3, 1:4): d 10.98 (s, 1H), 8.60 (s, 1H), 7.39–6.76 (m, 8H), 6.32 (s,
1H), 5.90 (s, 1H), 4.26 (s, 2H), 3.74 (s, 3H); 13C NMR (75 MHz, DMSO): d 182.1,
172.3, 156.6, 149.2, 139.3, 133.5, 130.3, 127.6, 126.7, 123.8, 122.1, 112.1, 111.7,
111.4, 110.0, 107.2, 94.2, 58.3, 53.3, 27.8; IR (KBr):
m 3330, 2929, 1618, 1510,
1457, 1249, 1031, 797, 762 cmÀ1; ESI-MS: m/z [M+1] 457.
2-((5-Chloro-1H-indol-3-yl)(4-methoxyphenyl)
methyl)-3-hydroxy-6-
(hydroxymethyl)-4H-pyran-4-one (4j): viscous liquid; 1H NMR (500 MHz,
DMSO + CDCl3, 1:4): d 10.37 (s, 1H), 6.73–7.42 (m, 8H), 6.39 (s, 1H), 5.90 (s,
1H), 5.22 (s, 1H), 4.30 (s, 2H), 3.76 (s, 3H); 13C NMR (75 MHz, DMSO): d 173.6,
167.0, 158.0, 150.8, 140.7, 134.6, 131.9, 129.1, 127.3, 125.7, 123.2, 121.1, 117.6,
26. Yadav, J. S.; Reddy, B. V. S.; Kumar, G. M. Synlett 2001, 1781.
27. Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Prabhakar, A.; Kunwar, A. C. Tetrahedron
Lett. 2003, 44, 2221.
113.7, 113.1, 108.9, 59.4, 54.9, 48.4, 45.6, 30.0, 28.9, 17.1; IR (KBr):
m 3355,
2930, 1621, 1578, 1510, 1459, 1249, 1181, 1030, 799, 763 cmÀ1; ESI-MS: m/z
28. Yadav, J. S.; Reddy, B. V. S.; Reddy, Ch. S. Tetrahedron Lett. 2004, 45, 4583.
29. Yadav, J. S.; Reddy, B. V. S.; Madan, Ch. New J. Chem. 2000, 24, 853.
30. General procedure: A mixture of aldehyde (1 mmol), kojic acid (1 mmol), indole
(1 mmol) and InCl3 (10 mol %) was stirred at 120 °C for a specified time as
required to complete the reaction (Table 1). After complete conversion, as
indicated by TLC, the reaction mixture was diluted with water and extracted
with ethyl acetate (2 Â 10 mL). The combined organic layers were dried over
anhydrous Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 60–120 mesh, ethyl acetate/hexane,
3:7) to afford the pure substituted aryl(Indolyl)kojic acid derivative.
2-((1H-Indol-3-yl)(phenyl)methyl)-3-hydroxy-6-(hydroxymethyl)-4H-pyran-4-
one (4a): solid, mp 78–80 °C; 1H NMR(500 MHz, DMSO + CDCl3, 1:4): d 10.86 (s,
1H), 8.77 (s, 1H), 6.9–7.31 (m, 10H), 6.31 (s, 1H), 5.98 (s, 1H), 5.28 (s, 1H), 4.22
(s, 2H); 13C NMR(75 MHz, DMSO): d 173.5, 167.1, 150.4, 141.4, 138.8, 135.1,
133.4, 129.5, 130.9, 128.1, 127.1, 120.1, 118.7, 118.4, 110.5, 108.8, 107.7, 59.3,
[M+1] 412.
3-Hydroxy-6-(hydroxymethyl)-2-((4-methoxy-
phenyl)(2-phenyl-1H-indol-3-
yl)methyl)-4H-pyran-4-one (4k): solid, mp 96–98 °C; 1H NMR (300 MHz,
DMSO + CDCl3, 1:4): d 11.12 (s, 1H), 7.82 (s, 1H), 7.62–6.63 (m, 13H), 6.37 (s,
1H), 6.09 (s, 1H), 4.28–4.05 (m, 2H), 3.72 (s, 3H); 13C NMR (75 MHz, DMSO): d
173.7, 167.4, 157.7, 151.0, 141.4, 136.7, 136.3, 132.0, 128.8, 128.6, 128.4, 127.9,
127.4, 121.3, 118.7, 113.7, 111.7, 111.3, 109.2, 108.8, 59.7, 59.4, 54.9, 48.4, 30.1,
29.0, 20.7, 17.1, 14.0; IR (KBr):
m 3325, 3060, 2923, 2855, 1715, 1619, 1455,
1313, 1093, 859, 748 cmÀ1; ESI-MS: m/z [M+1] 454.
3-Hydroxy-6-(hydroxymethyl)-2-(1-(2-phenyl-1H-indol-3-yl)propyl)-4H-pyran-
4-one (4l): solid, mp 85–87 °C; 1H NMR (300 MHz, DMSO + CDCl3, 1:4): d 10.58
(s, 1H), 7.8–6.9 (m, 9H), 6.4 (s, 1H), 4.59 (t, 1H, J = 7.9 Hz), 4.45–4.26 (m, 2H),
2.28–2.10 (m, 2H), 0.79 (t, 3H, J = 7.9 Hz); 13C NMR (75 MHz, DMSO): d 174.1,
167.6, 152.9, 141.2, 136.7, 136.5, 133.1, 131.2, 129.6, 128.9, 128.1, 127.6, 121.7,
121.2, 119.2, 111.7, 110.5, 109.0, 60.2, 30.0, 18.9, 14.5, 12.7; IR (KBr):
m 3301,
38.2, 11.7; IR (KBr):
MS: m/z [M+1] 347.
2-((1H-Indol-3-yl)(4-methoxyphenyl)methyl)-3-hydroxy-6-(hydroxymethyl)-4H-
m
3327, 2923, 2855, 1715, 1619, 1456, 1203, 748 cmÀ1; ESI-
2965, 2871, 1621, 1572, 1454, 1203, 1092, 986, 857, 746 cmÀ1; ESI-MS: m/z
[M+1] 376.
3-Hydroxy-6-(hydroxymethyl)-2-((2-hydroxy- phenyl)(2-phenyl-1H-indol-3-

B. V. Subba Reddy et al. / Bioorg. Med. Chem. Lett. 20 (2010) 7507–7511
7511
yl)methyl)-4H-pyran-4-one (4m): solid, mp 97–99 °C; 1H NMR (300 MHz,
DMSO + CDCl3, 1:4): d 11.03 (s, 1H), 9.08 (s, 1H), 7.6–6.6 (m, 13H), 6.30 (s, 1H),
6.20 (s, 1H), 4.16 (s, 2H); 13C NMR (75 MHz, DMSO): d 173.9, 167.0, 155.2,
152.1, 141.6, 136.5, 133.3, 129.8, 128.9, 128.1, 128.0, 126.9, 121.5, 120.4, 119.4,
31. National Committee for Clinical Laboratory (NCCL). Methods for Dilution
Antimicrobial Susceptibility Tests for Bacteria, which Grows Aerobically, 5th ed.;
Approved Standard M7-A5, NCCLS: Villanova, PA, 2000.
32. Linday, M. E. Practical Introduction to Microbiology; E and F. N. Spon Ltd: United
Kingdom, 1962.
119.0, 115.2, 111.7, 109.5, 109.3, 59.9, 36.1, 14.5; IR (KBr):
m 3388, 2920, 1651,
1616, 1570, 1510, 1455, 1370, 1198, 1083, 1029, 859, 740 cmÀ1; ESI-MS: m/z
[M+1] 440.