Molecular iodine as a versatile reagent for the synthesis of thiazoloquinoline-A potential antibacterial agent

Article abstract of DOI:10.1080/10426507.2010.503209

A series of 3-(2-aminothiazol-4-yl)quinolin-2[1H]-ones 3 was prepared by neat reaction of quinolin-2[1H]-ones 1 with thioureas 2 in the presence of molecular iodine. The synthesized compounds were evaluated for their in vitro antimicrobial activities against Escherichia coli, Paedococcus sp., Lactobacillus, Yersinia enterocolitica, and Staphylococcus aureus. The green chemical approach for the synthesis of thiazoloquinolinone 3 was performed under neat conditions using molecular iodine as catalyst as well as reaction medium. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.503209

This article was downloaded by: [Laurentian University]
On: 06 December 2014, At: 11:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Molecular Iodine as a Versatile Reagent
for the Synthesis of Thiazoloquinoline—A
Potential Antibacterial Agent
R. Subashini a & F. Nawaz Khan a
a Organic and Medicinal Chemistry Laboratory, School of Advanced
Sciences , VIT University , Vellore, Tamil Nadu, India
Published online: 07 Mar 2011.
To cite this article: R. Subashini & F. Nawaz Khan (2011) Molecular Iodine as a Versatile Reagent for
the Synthesis of Thiazoloquinoline—A Potential Antibacterial Agent, Phosphorus, Sulfur, and Silicon
and the Related Elements, 186:3, 450-456, DOI: 10.1080/10426507.2010.503209
To link to this article: http://dx.doi.org/10.1080/10426507.2010.503209
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 186:450–456, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.503209
MOLECULAR IODINE AS A VERSATILE REAGENT FOR
THE SYNTHESIS OF THIAZOLOQUINOLINE—A
POTENTIAL ANTIBACTERIAL AGENT
R. Subashini and F. Nawaz Khan
Organic and Medicinal Chemistry Laboratory, School of Advanced Sciences,
VIT University, Vellore, Tamil Nadu, India
GRAPHICAL ABSTRACT
3'
2'
5'
6'
4'
1'
S
S
N
O
O
NHR3
H2N
NHR3
R1
R1
5
4
2(a-c)
6
3
2
1
8
N
Method A / B
N
O
R2
R2
3(a-i)
1(a-g)
Compound
R1
R2
R3
1 or 3
-Cl
-Cl
-Cl
-Cl
-Cl
-Cl
-H
-CH3
-CH3
-H
a
b
c
d
e
f
-CH3
-NH2
-H
-CH3
-C2H5
-C2H5
-CH2Ph
-CH3
-CH3
-CH3
-H
g
h
i
-H
-CH3
-CH3
-H
-H
-C2H5
Abstract A series of 3-(2-aminothiazol-4-yl)quinolin-2[1H]-ones 3 was prepared by neat re-
action of quinolin-2[1H]-ones 1 with thioureas 2 in the presence of molecular iodine. The
synthesized compounds were evaluated for their in vitro antimicrobial activities against Es-
cherichia coli, Paedococcus sp., Lactobacillus, Yersinia enterocolitica, and Staphylococcus
aureus. The green chemical approach for the synthesis of thiazoloquinolinone 3 was performed
under neat conditions using molecular iodine as catalyst as well as reaction medium.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords 2-Aminothiazole, 3-(2-aminothiazol-4-yl)quinolin-2(1H)-ones; antibacterial activ-
ity; quinoline; thioureas
Received 13 April 2010; accepted 18 June 2010.
The authors wish to express their gratitude to the Indian Institute of Science, SAIF, Bangalore and Indian
Institute of Technology, Chennai and Syngene International Limited for their support of NMR, HRMS facilities.
Address correspondence to F. Nawaz Khan, Organic and Medicinal Chemistry Laboratory, School of Ad-
vanced Sciences, VIT University, Vellore, Tamil Nadu 632014, India. E-mail: nawaz f@yahoo.co.in
450

MOLECULAR IODINE AS A VERSATILE REAGENT
451
INTRODUCTION
The quinolinenucleus occurs in several natural compounds and pharmacologically ac-
tive substances1 displaying a broad range of biological activities such as antiasthmatic,2 anti-
inflammatory,3 antimalarial,4 anticancer,5 antibiotic,6 antihypertensive,7 and anti-HIV.8,9 As
a result, several simple and elegant syntheses of substituted quinolines have recently been
published.10 Several drugs based on the quinoline structure have improved therapy of
protozoal diseases, especially malaria.11
Similarly, the thiazole ring, a structural component of natural compounds such as
vitamin B1 (thiamine), penicillin, and carboxylase, has been found to exhibit significant
biological activities such as cytotoxic, immunosuppressive, antifungal, and enzyme in-
hibitory activity.12 Moreover, among the different aromatic heterocycles, thiazoles occupy
a prominent position in the drug discovery process,13 and this ring structure is found in
several marketed drugs. Aminothiazoles are known to be ligands of estrogen receptors14 as
well as a novel class of adenosine receptor antagonists.15
In continuation of our interest in heterocyclic molecules,16–24 in this article, we report
a simple and facile, one-pot, two-step, synthesis of novel 3-(2-aminothiazol-4-yl)quinolin-
2(1H)-ones 3a–i. Their in vitro antibacterial properties were screened and evaluated. In the
present synthesis, iodine played a major role in the one-pot synthesis, resulting in good
yields of target compounds.
RESULTS AND DISCUSSION
The synthetic protocol of the title compounds is shown in Scheme 1. The starting
material, N-alkylated quinolin-2[1H]-one 1, synthesized by using DMF/K2CO3, readily
reacted with thioureas 2 in the presence of iodine under solvent free conditions to give 3-(2-
aminothiazol-4-yl)quinolin-2[1H]-ones 3. The optimization of the reaction was carried out
using bromine (Method A) or iodine (Method B). It should be noted that the reaction of N-
alkylated quinolin-2[1H]-one 1 with thioureas 2 in the presence of bromine gave less yield
of the compound 3, even after heating for a prolonged reaction time. However, under iodine-
mediated conditions, the notorious substrate 1 gave a good yield of thiazolylquinolinone
3 with high purity. All additional attempts to increase the yield in this reaction, however,
proved to be futile. Iodine played a major role in the formation of compound 3, through
an iodoacetyl intermediate that condenses with thiourea. Moreover the reaction work up
was simpler, i.e., water was added to the reaction mixture and boiled for few minutes so
that the product thiazoles were dissolved in distilled water, which was filtered while hot.
The filtrate, when neutralized with aqueous NH3, gave the title compounds 3 in high yield
3'
2'
5'
6'
4'
1'
S
S
N
O
O
NHR3
H2N
NHR3
R1
R1
5
4
2(a-c)
6
3
2
1
8
N
Method A/B
N
O
R2
R2
3(a-i)
1(a-g)
Scheme 1 Synthesis of 3-(2-aminothiazol-4-yl)quinolin-2(1H)-ones.

452
R. SUBASHINI AND F. NAWAZ KHAN
Table 1 Substitutents of 3-(2-aminothiazol-4-yl)-quinolin-2[1H]-ones
Compound 1 or 3
R1
R2
R3
a
b
c
d
e
f
g
h
i
-Cl
-Cl
-Cl
-Cl
-Cl
-Cl
-H
-CH3
-CH3
-CH3
-C2H5
-C2H5
-CH2Ph
-CH3
-CH3
-C2H5
-H
-CH3
-NH2
-H
-CH3
-CH3
-H
-H
-H
-CH3
-H
1
(Table 1). All the synthesized final compounds were confirmed by FTIR, H NMR, 13C
NMR and mass spectral studies. Compound 3a showed FTIR bands at 3296, 1639, 1518
cm−1 due to NH2, C O, and C N respectively. The disappearance of C O at
1705 cm−1 of 1a at C-3 indicates that it had been involved in condensation with thiourea.
1H NMR spectrum of 3a showed at δ 3.68 (s, 3H, N CH3), 6.10 (s, 1H, CH-thiazole),
and 6.65 (s, 2H, NH2).
CONCLUSIONS
This article reports the successful green chemical approach for the synthesis of new
3-(2-aminothiazol-4-yl)quinolin-2[1H]-ones 3 using molecular iodine as catalyst under
neat condition. The antibacterial activity study revealed that compounds 3a and 3c showed
good activity against S. aureus. Compound 3c exhibits moderate activity against B. subtilis
and Paedococcus, in comparison to the standard drug ampicillin (see the Supplemental
Materials, available online).
EXPERIMENTAL
All reagents were purchased from Aldrich Chemical Co. Solvents used were pur-
chased from Rankem Chemicals. TLC was performed on silica gel coated on plates and
dried. (SD Fine chemicals). The plates were illuminated under an iodine chamber. Melting
points (mp) are uncorrected and were determined using an Elchem Microprocessor–based
DT apparatus. FT-IR spectra, as KBr pellets, were recorded on a Nucon Infrared spec-
1
trophotometer. H NMR (400 and 500 MHz) spectra were recorded on a Bruker 400 and
500 MHz spectrometer in CDCl3 or DMSO (with TMS for 1H as internal references).
General Procedure for the Synthesis of 3-(2-Aminothiazol-4-yl)-
quinolin-2[1H]-ones 3 (a–i)
Method A. To a mixture of N-substituted quinolin-2[1H]-ones 1 (1 mmol) and
thioureas 2 (20 mmol), bromine (20 mmol) was added dropwise. Then the mixture was
heated on a water bath overnight. Reaction completion was monitored by TLC using pet.
ether:EtOAc (3:2). Upon completion of the reaction, water was added and refluxed on a
water bath and filtered while hot. Then the solution was made alkaline by adding a strong

MOLECULAR IODINE AS A VERSATILE REAGENT
453
ammonia solution. The solid separated was filtered and purified by column chromatography
to afford products 3a–i as yellow amorphous solids (38–41% yield).
Method B. A mixture of N-substituted quinolin-2[1H]-ones 1 (1 mmol), thioureas
2 (20 mmol), and iodine (10 mmol) was heated on water bath for 6–8 h. The reaction
completion was monitored by TLC using pet. ether:EtOAc (3:2). The mixture was cooled
and diluted with water, then heated until most of the solid dissolved. It was filtered while
hot, then the filtrate was cooled and made alkaline by adding a strong ammonia solution.
The solid was filtered, washed with water, and recrystallized form acetone to afford products
3a–i as yellow amorphous solids (78–89% yield). The purity of quinolinone-thioazoles was
ascertained by spectral analysis (Scheme 2).
I2
O
O
R1
R1
CH3
HI
CH2I
N
O
N
O
S
R2
R2
H2N
NHR3
(2a-c)
1(a, g)
H2O
SH
NHR3
H2N
S
N
I
SH
NHR3
NHR3
HI
R1
R1
N
N
O
N
O
R2
R2
H2O
3(a-i)
Excess
I2
Scheme 2 Plausible mechanistic pathway for the formation of thiazoloquinolinones 3a–i.
1-Methyl-3-(2-aminothiazol-4-yl)-4-phenyl-6-chloroquinolin-2(1H)-one
(3a). Yield: 89%. Mp: 210◦C. IR (KBr, cm−1) υ: 3296 ( NH2), 1639 ( C O), 1518
1
( C N). H NMR (400 MHz, DMSO-d6, δ, ppm): 3.68 (s, 3H, N CH3); 6.10 (s, 1H,
CH-Thiazole); 6.65 (s, 2H, NH2); 6.95 (s, 1H, CH-5); 7.18 (m, 2H, CH-2ꢀ, CH-6ꢀ);
7.36 (m, 3H, CH-3ꢀ, CH-4ꢀ, CH-5ꢀ); 7.65 (m, 2H, CH-7, CH-8). 13C NMR (100 MHz,
DMSO-d6, δ, ppm): 30.3 (N-CH3), 107.3 (C-5-Thiazole), 117.5, 122.1, 126.4, 126.7, 2
× 128.4, 128.7, 2 × 129.4, 130.7, 135.8 (C-Cl), 136.0, 138.4 (C-4- Thiazole), 145.0,
147.4, 160.3 ( C O), 167.1 (C-NH2). Mol. formula: C19H14ClN3OS requires 367.0546:
HRMS: m/z 367.1063 (M+).
1-Methyl-3-(2-(methylamino)thiazol-4-yl)-4-phenyl-6-chloroquinolin-2
(1H)-one (3b). Yield: 82.3%. Mp: 130–132◦C. IR (KBr, cm−1) υ: 3371 ( NH), 1632

454
R. SUBASHINI AND F. NAWAZ KHAN
1
( C O), 1513 ( C N). H NMR (400 MHz, CDCl3, δ, ppm): 2.82 (s, 3H, Thiazole
-N-CH3); 3.80 (s, 3H, N-CH3); 5.13 (s, 1H, -NH); 6.16 (s, 1H, CH- Thiazole); 7.18 (m,
2H, CH-5, CH-7); 7.37 (m, 5H, CH-2ꢀ, 3ꢀ, 4ꢀ, 5ꢀ, 6ꢀ); 7.49—7.51 (d, 1H, CH-8). 13C NMR
(100 MHz, CDCl3, δ, ppm): 30.2 (Thiazole -N-CH3), 32.6 (N-CH3), 109.1, 114.5, 122.0,
124.7, 2 × 128.2, 128.5, 3 × 130.2, 2 × 130.1, 130.5, 131.4, 135.2, 141.8, 164.1 (C O),
164.8 (C-NH2). Mol. formula: C20H16ClN3OS requires 381.0703 : HRMS: m/z 381.1352
(M+).
1-Methyl-3-(2-hydrazinothiazol-4-yl)-4-phenyl-6-chloroquinolin-2(1H)-
one (3c). Yield: 79.6%. Mp: 250–252◦C. IR (KBr, cm−1) υ: 3436 ( NH), 3357 ( NH2),
1637 ( C O), 1572 ( C N). 1H NMR (400 MHz, CDCl3, δ, ppm): 2.01—2.03 (d, 2H,
J = 8 Hz, NH2- Thiazole); 3.80 (s, 3H, N-CH3); 7.01 (s, 1H, CH- Thiazole); 7.17 (m,
2H, CH-5,7); 7.50 (m, 5H, CH-2ꢀ, 3ꢀ, 4ꢀ, 5ꢀ, 6ꢀ); 7.61–7.63 (d, 1H, CH-8); 8.42 (t, 1H,
NH- Thiazole). 13C NMR (100 MHz, CDCl3, δ, ppm): 30.6 (N-CH3), 109.1, 114.5, 122.0,
124.7, 2 × 128.2, 128.5, 3 × 130.2, 2 × 130.1, 130.5, 131.4, 135.2, 141.8, 164.1 (C O),
164.8 (C-NH2). Mol. formula: C19H15ClN4OS requires 382.0655 : HRMS: m/z 381.9078
(M+).
1-Ethyl-3-(2-aminothiazol-4-yl)-4-phenyl-6-chloroquinolin-2(1H)-one (3d).
Yield: 82.1%. Mp: 170–172◦C. IR (KBr, cm−1) υ: 3437 ( NH2), 1629 ( C O), 1519
( C N). 1H NMR (500 MHz, DMSO-d6, δ ppm): 1.26 (t, 3H, N-CH2CH3); 4.34 (q, 2H,
N-CH2CH3); 6.10 (s, 1H, CH- Thiazole); 6.69 (s, 2H, -NH2); 6.97 (s, 1H, CH-5); 7.19
(m, 2H, CH-2ꢀ, 6ꢀ); 7.38 (m, 3H, CH-3ꢀ, 4ꢀ, 5ꢀ); 7.69 (m, 2H, CH-7,8). 13C NMR (125
MHz, CDCl3, δ, ppm): 13.0 (N-CH2CH3), 37.9 (N-CH2CH3), 107.4, 117.2, 122.4, 2 ×
126.2, 127.0, 3 × 128.4, 2 × 129.4, 2 × 130.8, 135.9, 137.3, 147.5, 159.8 (C O), 167.1
(C-NH2). Mol. formula: C20H16ClN3OS requires 381.0703 : (ESI): HRMS: m/z 381.5604
(M+).
1-Ethyl-3-(2-(methylamino)thiazol-4-yl)-4-phenyl-6-chloroquinolin-2(1H)-
one (3e). Yield: 80.7%. Mp: 140◦C. IR (KBr, cm−1) υ: 3432 (-NH2), 1632 ( C O),
1556 ( C N). 1H NMR (500 MHz, DMSO-d6, δ, ppm): 1.25 -1.28 (t, 3H, N-CH2CH3);
2.49 (s, 3H, 2ꢀNH-CH3); 4.34–4.36 (q, 2H, N-CH2CH3); 6.45 (s, 1H, CH- Thiazole); 6.97
(s, 1H, -NH); 7.37 (m, 3H, CH-5, 2ꢀ, 6ꢀ); 7.38 (m, 3H, CH-3ꢀ, 4ꢀ, 5ꢀ); 7.66 (m, 2H, CH-7,8).
13C NMR (125 MHz, CDCl3, δ, ppm): 13.1 (N-CH2CH3), 30.3 (Thiazole-N-CH3), 37.3
(N-CH2CH3), 109, 114.1, 121.9, 124.1, 2 × 127.9, 128.0, 3 × 129.8, 2 × 130, 130.2,
130.9, 135, 140.9, 163.5 (C O), 164.5 (C-NH-). Mol. formula: C21H18ClN3OS requires
395.0859 : HRMS: m/z 395.6901 (M+).
1-Benzyl-3-(2-(methylamino)thiazol-4-yl)-4-phenyl-6-chloro-quinolin-2
(1H)-one (3f). Yield: 78.2%. Mp: 222–226◦C. IR (KBr, cm−1) υ: 3462 (-NH2),
1623( C O), 1515( C N). 1H NMR (500 MHz, CDCl3, δ, ppm): 5.41 (s, 2H, N-CH2);
6.12 (s, 1H, CH- Thiazole); 6.40 (s, 1H, -NH2); 7.23 (d, 1H, CH-7, J = 2.5); 7.27 (s, 1H,
CH-5); 7.36 (m, 5H, Ar-H, -CH2-Ph); 7.51 (m, 5H, Ar-H, 4-Ph); 7.74 (d, 1H, CH-8, J =
2.5). 13C NMR (125 MHz, CDCl3, δ, ppm): 48.1 (N-CH2-C6H5), 30.3 (Thiazole-N-CH3),
108.8, 114.3, 121.7, 124.3, 5 × 127.8, 3 × 128.2, 3 × 129.9, 3 × 130.1, 130.4, 130.9,
134.9, 140.7, 163.2 (C O), 164.9 (C-NH-). Mol. formula: C26H20ClN3OS requires
457.1016 : HRMS: m/z 457.0097 (M+).
1-Methyl-3-(2-aminothiazol-4-yl)-4-phenylquinolin-2(1H)-one
(3g).
Yield: 81%. Mp: 167–169◦C. IR (KBr, cm−1) υ: 3439 ( NH2), 1631 ( C O),1503
1
( C N). H NMR (500 MHz, DMSO-d6, δ, ppm); 3.81 (s, 3H, N-CH3); 5.53 (s, 2H,
-NH2); 6.05 (s, 1H, CH- Thiazole); 7.40 (m, 9H, Ar-H). 13C NMR (125 MHz, CDCl3, δ,
ppm): 30.2 (N-CH3), 108.9, 121.8, 3 × 127.7, 3 × 129.7, 3 × 130.1, 2 × 130.3, 130.8,

MOLECULAR IODINE AS A VERSATILE REAGENT
455
135.2, 140.7, 163.3 (C O), 164.2 (C-NH2). Mol. formula: C19H15N3OS requires 333.0936
: HRMS: m/z 333.4634 (M+).
1-Methyl-3-(2-(methylamino)thiazol-4-yl)-4-phenylquinolin-2(1H)-one
(3h). Yield: 79%. Mp: 233◦C. IR (KBr, cm−1) υ: 3392 ( NH), 1637 ( C O), 1506
( C N). 1H NMR (500 MHz, DMSO-d6, δ, ppm); 2.72 (s, 3H, 2ꢀ-NHCH3); 3.81 (s, 3H,
N-CH3); 5.80 (s, 1H, NH); 6.18 (s, 1H, CH-5ꢀ); 7.02–7.57 (m, 9H, Ar-H). 13C NMR
(125 MHz, DMSO, δ, ppm): 30.7 (N-CH3), 107.7 (C-5-Thiazole), 117.2, 122.4, 126.2,
126.9, 2 × 128.5, 3 × 128.9, 2 × 129.7, 133, 136.1, 138.0 (C-4- Thiazole), 145.2, 147.8,
161.5 (-C O), 169 (C-NH2). Mol. formula: C20H17N3OS requires 347.1092 : HRMS: m/z
347.3448 (M+).
1-Ethyl-3-(2-aminothiazol-4-yl)-4-phenylquinolin-2(1H)-one (3i). Yield:
80.3%. Mp: 194–196◦C. IR (KBr, cm−1) υ: 3439 ( NH2), 1631 ( C O), 1503 ( C N).
1H NMR (500 MHz, DMSO-d6, δ, ppm): 1.48 (t, 3H, N-CH2CH3); 2.80 (q, 2H,
N-CH2CH3), 4.41 (s, 2H, -NH2), 6.17 (s, 1H, CH- Thiazole), 7.37 (m, 9H, Ar-H). 13C
NMR (125 MHz, CDCl3, δ, ppm): 13 (N-CH2CH3), 37.5 (N-CH2CH3), 107.2, 122.1,
127.4, 3 × 128.0, 128.2, 3 × 129.4, 2 × 129.5, 130.6, 131.2, 138.3, 139, 162 (C O), 163
(C-NH2). Mol. formula: C20H17N3OS requires 347.1092 : HRMS: m/z 346.8739(M+).
REFERENCES
1. (a) Maguire, M. P.; Sheets, K. R.; Vety, K. M.; Spada, A. P.; Zilberstein, A. J. Med. Chem. 1994,
37, 2129–2137; (b) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia, M. Eur. J. Med.
Chem. 2000, 35, 1021–1035 (c) Chen, Y. L.; Fang, K. C.; Sheu, J. Y.; Hsu, S. L.; Tzeng, C. C. J.
Med. Chem. 2001, 44, 2374–2377.
2. Doube, D.; Blouin, M.; Brideau, C.; Chan, C.; Desmarais, C.; Ethier, D.; Falgueyret, J. P.; Friesen,
R. W.; Girard, M.; Girard, Y.; Guay, J.; Tagari, P.; Young, R. N. Bioorg. Med. Chem. Lett. 1998,
8, 1255–1260.
3. Leatham, P. A.; Bird, H. A.; Wright, V.; Seymour, D.; Gordon, A. Eur. J. Rheumatol. Inflamm.
1983, 6, 209–211.
4. Arcadi, A.; Chiarini, M.; Giuseppe, S. D.; Marinelli, F. Synlett 2003, 203–206, and references
cited therein.
5. Denny, W. A.; Wilson, W. R.; Ware, D. C.; Atwell, G. J.; Milbank, J. B.; Stevenson, R. J. U.S.
Patent, 7064117, 2006.
6. Mahamoud, A.; Chevalier, J.; Davin-Regli, A.; Barbe, J.; Pages, J.-M. Current Drug Targets
2006, 7, 843–847.
7. Muruganantham, N.; Sivakumar, R.; Anbalagan, N.; Gunasekaran, V.; Leonard, J. T. Biol. Pharm.
Bull. 2004, 27, 1683–1687.
8. Wilson, W. D.; Zhao, M.; Patterson, S. E.; Wydra, R. L.; Janda, L.; Strekowski, L. Med. Chem.
Res. 1992, 2, 102–110.
9. Strekowski, L.; Mokrosz, J. L.; Honkan, V. A.; Czarny, A.; Cegla, M. T.; Patterson, S. E.; Wydra,
R. L.; Schinazi, R. F. J. Med. Chem. 1991, 34, 1739–1746.
10. (a) Lin, X. F.; Cui, S. L.; Wang, Y. G. Tetrahedron Lett. 2006, 47, 3127–3130; (b) Sakai, N.; Aoki,
D.; Hamajima, T.; Konakahara, T. Tetrahedron Lett. 2006, 47, 1261–1265; (c) Sakai, N.; Annaka,
K.; Konakahara, T. J. Org. Chem. 2006, 71, 3653–3655; (d) Tanaka, S. Y.; Yasuda, M.; Baba,
A. J. Org. Chem. 2006, 71, 800–803 (e) Wang, G. W.; Jia, C. S.; Dong, Y. W. Tetrahedron Lett.
2006, 47, 1059–1063; (f) Wang, X.; Dixon, S.; Kurth, M. J.; Lam, K. S. Tetrahedron Lett. 2005,
46, 5361–5364; (g) De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 1647–1649; (h) Taguchi,
K.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 2005, 46, 4539–4542; (i) Kobayashi, K.; Yoneda,
K.; Miyamoto, K.; Morikawa, O.; Konishi, H. Tetrahedron 2004, 60, 11639–11645; (j) Zhang,
X.; Campo, M. A.; Yao, T.; Larock, R. C. Org. Lett. 2004, 7, 763–766.

456
R. SUBASHINI AND F. NAWAZ KHAN
11. Basco, L. K.; Dechy-Cabaret, O.; Ndounga, M.; Meche, F. S.; Robert, A.; Meunier, B. Antimicrob.
Agents Chemother. 2001, 45, 1886–1888.
12. Sperry, J. B.; Wright, D. L. Curr. Opin. Drug. Discovery Dev. 2005, 8, 723–740.
13. Dolle, R. E.; Le Bourdonnec, B.; Morales, G. A.; Moriarty, K. J.; Salvino, J. M. J. Comb. Chem.
2006, 8, 597–635.
14. Fink, B. A.; Mortensen, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol.
1999, 6, 205–219.
15. Van Muijlwijk-Koezen, J. E.; Timmerman, H.; Vollinga, R. C.; Von Drabbe Kunzel, J. F.; De
Groote, M.; Visser, S.; Ijzerman, A. P. J. Med. Chem. 2001, 44, 749–762.
16. Patil, N. T.; Nawaz Khan, F.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 8497–8499.
17. Nawaz Khan, F.; Jayakumar, R.; Pillai, C. N. J. Mol. Catal. A, Chem. 2003, 195, 139–145.
18. Nawaz Khan, F.; Jayakumar, R.; Pillai, C. N. Tetrahedron Lett. 2002, 43, 6807–6809.
19. Hathwar, V. R.; Manivel, P.; Nawaz Khan, F.; Guru Row, T. N. Acta Cryst. 2007, E63, o3707.
20. Hathwar, V. R.; Manivel, P.; Nawaz Khan, F.; Guru Row, T. N. Acta Cryst. 2007, E63, o3708.
21. Syed Tajudeen, S.; Nawaz Khan, F. Synth. Commun. 2007, 37, 3649–3656.
22. Maiyalagan, T.; Hathwar, V. R.; Manivel, P.; Burcu Arslan, N.; Nawaz Khan, F. Acta Cryst. 2008,
E65, o128.
23. (a) Manivel, P.; Roopan, S. M.; Nawaz Khan, F. J. Chil. Chem. Soc. 2008, 53, 1609–1610;
(b) Manivel, P.; Roopan, S. M.; Nawaz Khan, F. Indian J. Heterocycl Chem. 2008, 18, 21–24;
(c) Roopan, S. M.; Maiyalagan, T.; Nawaz Khan, F. Can. J. Chem. 2008, 86, 1019–1025.
24. (a) Roopan, S. M.; Reddy, B. R.; Kumar, A. S.; Khan, F. N. Indian J. Heterocy Chem. 2009, 19,
81–82; (b) Roopan, S. M.; Khan, F. N.; Mandal, B. K. Tetrahedron Lett. 2010, 51, 2309–2311;
(c) Roopan, S. M.; Khan, F. N. Arkivoc 2009, 13, 161–169.