Enantioselective 1,4-addition of kojic acid derivatives to β-nitroolefins catalyzed by a cinchonine derived sugar thiourea

Article abstract of DOI:10.1039/c3ra47423b

A highly enantioselective Michael addition reaction of kojic acid derivatives to β-nitroolefins has been accomplished using a cinchonine derived sugar thiourea. The reaction provides the corresponding Michael adducts in excellent yields with a high degree

Full text of DOI:10.1039/c3ra47423b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Enantioselective 1,4-addition of kojic acid
derivatives to b-nitroolefins catalyzed by a
Cite this: RSC Adv., 2014, 4, 9107
cinchonine derived sugar thiourea†
a
B. V. Subba Reddy, S. Madhusudana Reddy,a Manisha Swain,a Srikanth Dudem,b
*
Shasi V. Kalivendib and C. Suresh Reddyc
A highly enantioselective Michael addition reaction of kojic acid derivatives to b-nitroolefins has been
accomplished using a cinchonine derived sugar thiourea. The reaction provides the corresponding
Michael adducts in excellent yields with a high degree of enantioselectivity (up to 99% ee) in short
reaction time with low catalyst loading. The Michael adducts are found to exhibit promising cytotoxicity
against various cancer cell lines.
Received 9th December 2013
Accepted 20th January 2014
DOI: 10.1039/c3ra47423b
www.rsc.org/advances
Inspired by recent advancements in thiourea catalysis we
herein report the asymmetric Michael addition of kojic acid
Introduction
derivatives to b-nitrostyrenes to produce the Michael adducts in
high yields with good to excellent enantioselectivity using a
novel series of cinchona derived sugar thiourea catalysts.
Initially, we investigated the catalytic efficiency of thiourea
catalysts I–XII (Fig. 1) was evaluated in the Michael addition of
kojic acid TBS ether (1) to b-nitrostyrene (2a). Remarkably, the
reaction proceeds at low concentration of the catalyst II with
enhanced reaction rates compared to previously reported
catalysts.15
Cinchona thioureas (I–XII) containing different chiral
diamine skeletons were chosen as the catalysts (Fig. 1).
Accordingly, treatment of kojic acid TBS ether (1) with b-nitro-
styrene (2a) in the presence of catalysts I and VII in CH2Cl2 at
30 ꢀC afforded the desired product 3a reasonably in good yield
with moderate ee (Table 1, entries a and s). Replacement of the
catalyst I and VII with IV and X gave the product 3a in low ee
with opposite asymmetric induction (Table 1, entries p and v).
The above reaction was further carried out with other catalysts
II, V, VIII and XI to evaluate their efficiency. But to our surprise,
the catalysts II and VIII gave the Michael adduct 3a in excellent
yields (85 and 80%) with good ee 75 and 71% respectively (Table
1, entries b and t).
The Michael addition is one of the most elegant approaches for
the construction of carbon\carbon bonds under mild condi-
tions in an atom economic fashion.1 In particular, asymmetric
Michael reaction2 of nitroalkenes is very attractive to produce
the enantiopure nitroalkanes which are important building
blocks for the synthesis of chiral amines.3 Recently, cinchona
derived thiourea catalysts have received special attention in the
eld of organocatalysis.4 Among them, sugar–cinchona hybrid
thiourea catalysts5 have proved to be highly efficient for the
enantioselective Michael reaction.
Kojic acid is a fungal metabolite and is known to exhibit a
broad spectrum of biological activities such as antimicrobial,6
cosmetics,7 pesticide/insecticide,8 antitumor,9 antidiabetic,10
and anticonvulsant activity.11 Consequently, a large number of
kojic acid derivatives have been prepared to evaluate their effi-
ciency in biological systems.12 In addition, kojic acid has also
been used for the synthesis of biologically active natural prod-
ucts.13 In fact, kojic acid acts as a highly reactive nucleophile in
1,4-addition reactions.14 On the other hand, asymmetric
Michael addition of kojic acid derivatives to nitroalkenes
provides a direct access to enantiomerically enriched nitro
compounds15 which are key intermediates for b-peptides.16
However, the catalysts V and XI gave the product 3a in
similar yields but with low ee (Table 1, entries q and w). The
efficiency of other cinchona bifunctional thiourea catalysts such
as III, VI, IX and XII was also tested in the above reaction. None
of them gave the 3a with satisfactory yields and enantiose-
lectivity (Table 1, entries o, r, u and x).
Aer numerous experiments, the catalyst II was found to be
superior in terms of yield and enantioselectivity (75% ee, Table
1, entry b) than other catalysts. With the best catalyst in hand,
we next screened the effect of other parameters like solvent,
temperature and catalyst loading. Of various solvents tested, the
aNatural Product Chemistry, Indian Institute of Chemical Technology, Uppal Road,
Tarnaka, Hyderabad, 500607, India. E-mail: basireddy@iict.res.in; Fax: +91 40
27160512
bCentre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road,
Tarnaka, Hyderabad, 500607, India
cDepartment of Chemistry, Sri Venkateswra University, Tirupati, India
† Electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR spectrum of products. Detailed procedures and spectroscopic data for
novel catalysts. Copies of 1H NMR, 13C NMR and HPLC data of novel
compounds and catalysts prepared are available. See DOI: 10.1039/c3ra47423b
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9107–9111 | 9107

View Article Online
RSC Advances
Paper
Table 1 Screening of thiourea catalysts in the Michael reaction of kojic
acid TBS ether (1) with b-nitrostyrene (2a)
Entry
Catalysta
Solvent
T (ꢀC)
Yield (%)b
ee (%)c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
I
II
II
II
II
II
II
II
II
II
II
II
II
II
III
IV
V
VI
VII
VIII
IX
X
CH2Cl2
CH2Cl2
PhCH3
Xylene
CH3CN
EtOH
THF
MeOH
Et2O
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
30
30
30
30
30
30
30
30
30
30
À10
0
75
85
89
90
91
94
93
96
71
97
96
97
98
98
71
74
84
76
76
80
78
72
79
76
68
75
78
85
79
85
78
89
67
91
97
98
5
5
99
99d
55
30
30
30
30
30
30
30
30
30
30
À56
À55
À45
67
71
54
À52
À56
À54
s
t
u
v
w
x
XI
XII
a
Reaction was carried out with 1 (0.2 mmol), 2a (0.22 mmol) in the
b
c
presence of 10 mol% of organocatalyst. Isolated yields. Determined
by chiral HPLC. d 5 mol% catalyst used.
reaction conditions for the Michael addition were determined
to be 0.1 mmol of the kojic acid TBS ether (1), 0.11 mmol of b-
nitrostyrene (2a), 5 mol% of the catalyst II in 1 mL i-PrOH at 5 ꢀC
for 7 h. The scope of the reaction was further investigated under
optimized conditions and the results are summarized in Table 2.
Notably, several aromatic nitroalkenes afforded the desired
Fig. 1 Representative bifunctional thiourea catalysts.
best results were achieved in i-PrOH, whereas the moderate products in high to excellent enantioselectivities (Table 2, 90–
enantioselectivity was observed in xylene, EtOH and MeOH. 99%, entries a–s) with (R)-conguration. The absolute congu-
However, poor yields and low enantioselectivity were obtained ration of the Michael products was assigned by comparison of
in toluene, CH3CN, THF and Et2O. Therefore, i-PrOH was the optical rotation with known compounds.15 It was found that
chosen as the optimal solvent for this reaction (91% ee). Indeed, nitroolens (2) either with electron-withdrawing or with elec-
the temperature was found to have a signicant inuence on tron-donating groups on the phenyl ring gave the products in
the enantioselectivity. For example, lowering the reaction good to excellent yields (85–99%) with high enantioselectivity
temperature to À10 ꢀC, the product 3a was obtained in 96% (84–99% ee). In addition, heteroaromatic substrates such as
yield with 97% ee (Table 1, entry k) aer a long reaction time. By 2-furanyl and 2-thienyl gave the Michael adducts with good
ꢀ
increasing the reaction temperature to 5 C, the reaction was yields and ee (Table 2, entries r and s). It is noteworthy to
complete in short time with a gradual increase of yield and ee mention that aliphatic nitroalkene also furnished the Michael
(Table 1, entry l and m). By decreasing the amount of the adduct with excellent selectivity (Table 2, entry t, 89% ee). A
catalyst from 10 to 5 mol% did not alter the yield and enan- large number of kojic acid derivatives (3a–3t) were prepared in
tioselectivity (98% of yield and 99% of ee, Table 1, entry n). high yields with excellent enantioselectivities (up to 99% ee).
Therefore, no signicant effect of the catalyst loading either on
Encouraged by the above results, we turned our attention to
yield or enantioselectivity was observed. Thus, the optimal evaluate the synthetic potential of catalyst II in Michael reaction
9108 | RSC Adv., 2014, 4, 9107–9111
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 2 Michael reaction of kojic acid TBS ether (1) with various
nitroolefins
Entry
R1
Producta
Yield (%)b
ee (%)c
Conf.
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
C6H5
4-FC6H4
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
97
98
97
95
90
95
96
95
99
98
96
97
93
92
95
94
90
94
85
90
99
96
94
94
91
91
85
88
95
88
91
88
91
84
87
91
95
95
92
89
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
S
4-ClC6H4
4-BrC6H4
4-MeC6H4
4-MeOC6H4
3-FC6H4
Fig. 2 A plausible ternary complex.
3-ClC6H4
2-FC6H4
carbohydrate of the catalyst II respectively through hydrogen
bonding. The nucleophilic attack of the enolate on b-nitro-
styrene from the Re-face leading to the formation of (R)-enan-
tiomer as a major product, which is consistent with the
observed results. The attack of enolate to the Si-face of the
nitroolen is restricted by cinchonine and carbohydrate
moieties of the catalyst. The carbohydrate serves as the chiral
auxiliary to enhance the selectivity. As shown in Fig. 2, the
complexation of cinchonine, thiourea and carbohydrate
moieties of the bifunctional catalyst with kojic acid and
nitroolen plays a signicant role in controlling the enantio-
selectivity of the Michael reaction.
2-ClC6H4
2-BrC6H4
2-MeOC6H4
2-Naphthyl
2-BnOC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
3,5-(Me)2C6H3
2-Furanyl
2-Thienyl
Butyl
s
t
3s
3t
a
Reaction was carried out with 1 (0.1 mmol), 2 (0.11 mmol), and in 1 mL
of i-PrOH. b Isolated yields. c Determined by chiral HPLC.
of 4a and 4b to b-nitrostyrene 2a. Interestingly, the reaction
proceeded effectively under present conditions to afford the
respective Michael products 5a and 5b in good yields (96–95%)
with excellent enantioselectivity (95–97%) (Table 3, entries a
and b).
Table 4 Anti-proliferative activity (IC50values mMb) of Michael adducts
on HeLa, A549, DU145, MCF7
Compounda
HeLa
A549
DU145
MCF7
3a
3b
53 Æ 2.1
>100
38 Æ 2.1
47 Æ 1.5
38 Æ 2.7
18 Æ 1.7
8.3 Æ 1.1
29 Æ 1.8
38 Æ 2.7
84 Æ 3.4
9.1 Æ 0.8
37 Æ 2.8
36 Æ 2.4
50 Æ 2.8
55 Æ 2.7
>100
37 Æ 2.4
32 Æ 1.9
>100
78 Æ 2.8
40 Æ 2.8
>100
31 Æ 1.7
40 Æ 2.6
51 Æ 2.9
16 Æ 0.8
13 Æ 1.4
51 Æ 2.7
>100
36 Æ 1.9
14 Æ 1.2
>100
34 Æ 2.6
63 Æ 2.7
38 Æ 2.8
45 Æ 2.6
33 Æ 2.4
>100
3.5 Æ 1.8
33 Æ 2.2
46 Æ 2.1
37 Æ 2.8
24 Æ 2.1
41 Æ 2.6
36 Æ 2.7
60 Æ 2.4
56 Æ 2.8
34 Æ 2.4
18 Æ 1.1
24 Æ 1.6
53 Æ 2.8
>100
44 Æ 2.5
35 Æ 2.4
>100
48 Æ 2.4
35 Æ 2.1
57 Æ 2.6
47 Æ 2.6
38 Æ 2.8
54 Æ 2.4
37 Æ 1.9
26 Æ 1.4
58 Æ 2.7
87 Æ 2.8
65 Æ 3.2
47 Æ 1.6
>100
Based on the above results, a possible ternary complex of
the catalyst II was proposed in Fig. 2. According to the results
reported in Table 2, it was believed that nitroolen could be
effectively activated by thiourea moiety of the catalyst, while
the tertiary amine deprotonates the enolic OH to generate the
kojic acid enolate. In a ternary complex, both nitroolen and
kojic acid coordinate with thiourea, tertiary amine and
3c (racemic)
37 Æ 2.3
11 Æ 1.5
9.2 Æ 1.1
15 Æ 1.2
27 Æ 1.7
34 Æ 1.8
10 Æ 0.9
51 Æ 2.6
92 Æ 3.3
31 Æ 2.8
22 Æ 2.1
56 Æ 2.4
75 Æ 2.9
63 Æ 3.7
33 Æ 2.5
24 Æ 1.7
27 Æ 1.8
58 Æ 3.1
82 Æ 2.9
28 Æ 2.3
22 Æ 1.1
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
5a
5b
Table 3 Enantioselective Michael addtion of kojic acid derivatives (4a
and b) to b-nitrostyrene (2a)
Entry
R2
Producta
Yield (%)b
ee (%)c
Conf.
43 Æ 1.8
>100
a
b
H
5a
5b
96
95
95
97
R
R
55 Æ 2.8
4-ClC6H4S–
a
Cell lines were treated with different concentration of compounds for
Reaction was carried out with 1 (0.1 mmol), 2 (0.11 mmol), and in 1 mL 48 h as described in experimental section. b IC50 values are indicated as
a
of i-PrOH. b Isolated yields. c Determined by chiral HPLC.
a mean value of three independent experiments.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9107–9111 | 9109

View Article Online
RSC Advances
Paper
organocatalyst for the asymmetric Michael addition of kojic
acid derivatives to b-nitroolens. Our approach has signicantly
improved the reaction rate to 7 h using a new quinine–sugar–
thiourea catalyst, whereas the reported reaction took four days
for the completion using cyclohexane-derived thiourea catalyst.
High enantioselectivity (99%), low catalyst loading (5 mol%),
excellent yields, short reaction times, broad substrate scope and
mild reaction conditions are the salient features of this meth-
odology. This is the rst report on the evaluation of anti-cancer
properties of the Michael adducts, which are found to exhibit
promising anti-cancer activity. Further application of sugar
thiourea catalysts for asymmetric synthesis is under progress in
our laboratory.
In vitro anticancer activity
The Michael adducts were evaluated for their anti-proliferative
activity against four different human tumor cell lines; HeLa
(human epithelial cervical cancer), A549 (human lung carcinoma
epithelial), DU145 (human prostate carcinoma epithelial), and
MCF-7 (human breast adenocarcinoma). The inhibitory
concentration (IC50) values are summarized in Table 4.
As evident from Table 4, the test compounds showed
moderate to good cytotoxicity against four different cancer cell
lines. The chiral compound 3c was highly active than its racemic
form. The study of % viability vs concentration of chiral and
racemic products of 3c is shown in Fig. 3. Compound 3c was
active against A549, DU145, MCF7 cell lines at 18 mM, 16 mM, and
18 mM respectively whereas 3c was active against HeLa cell lines at
11 mM. Furthermore, compound 3d showed good activity against
HeLa, A549 and DU145 cell lines at 9 mM, 8 mM, and 13 mM
respectively while compound 3h was also active against A549,
HeLa and Du145 cell lines at 9 mM, 10 mM and 14 mM respectively.
Experimental
General. All reactions were carried out under nitrogen atmo-
sphere. Commercial reagents were used as received, unless
otherwise stated. 1H NMR spectra were recorded on 300 MHz or
500 MHz spectrometer using CDCl3 and DMSO-d6 as a solvent.
13C NMR were recorded on 75 MHz and 125 MHz spectrometer
using CDCl3 and DMSO-d6. TMS was used as an internal refer-
ence for 1H NMR analysis. All the compounds were puried by
column chromatography on silica gel (60–120 mesh) using
hexane–ethyl acetate mixture as eluent. Mass analysis was
carried out using ESI mass spectrometer. Infrared (IR) spectra
were recorded on FT-IR spectrometer. Optical rotations were
measured using Rudolph (Digipol 781 M6U) polarimeter. The ee
values were determined by chiral high-performance liquid
chromatography (HPLC) using Daicel Chiracel OJ-H.
Conclusion
In conclusion, a novel bifunctional cinchona–sugar based
thiourea catalyst has proved to be
a highly efficient
Materials and methods
Cell culture and maintenance
All cell lines used in this study were purchased from the
American Type Culture Collection (ATCC). A549m (human lung
carcinoma epithelial) and HeLa (human epithelial cervical
cancer) were grown in Dulbecco's modied Eagle's medium
(DMEM) containing non-essential amino acids and 10% FBS.
MCF-7 (human breast adenocarcinoma) and DU145 (human
prostate carcinoma epithelial) cells were cultured in Eagle's
minimal essential medium (MEM) containing non-essential
amino acids, 1 mM sodium pyruvate, and 10% FBS. All cell lines
maintained in humidied atmosphere of 5% CO2 at 37 ꢀC. Cells
were trypsinized when sub conuent from T75 asks per 90 mm
dishes and seeded in 96 well plate at a concentration of 1 Â 104
cells mLÀ1 in complete medium, treated with compounds at
desired concentrations and harvested as required.17
Cell proliferation assay using MTT
The assay is a quantitative colorimetric method for the determi-
nation of cell survival and proliferation. Metabolically active cells
reduce pale yellow tetrazolium salt (MTT) to a dark blue water-
insoluble formazan, which is quantied aer solubilisation with
DMSO. The absorbance of the solubilized formazan directly
correlates with a number of viable cells. Cells were plated at a
Fig. 3 Effect of chiral and racemic forms of 3c on cell viability. Four
different cancer cell lines were treated with compounds in concen-
tration dependent manner (1 mM, 10 mM, 25 mM) for 48 h in 96 well plate
followed by MTT assay.
9110 | RSC Adv., 2014, 4, 9107–9111
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
density of 1 Â 104 cells in 200 mL of medium per well of 96-well
plate. The 96-well microtiter plate was incubated for 24 h prior to
addition of the experimental compounds. Cells were treated at
different concentrations (1, 10 and 25 mM) of the test compounds
for 48 hours. The assay was terminated with the addition of MTT
(5%, 10 mL) and incubated for 60 min at 37 ꢀC. The supernatant
was aspirated and plates were air dried. MTT-formazon crystals
were dissolved in 100 mL DMSO. The optical density (O.D) was
measured at 560 nm using TECAN multimode reader. The growth
percentage of each treated well of 96 well plate was calculated
27, 445; (d) A. Fassihi, D. Abedi, L. Saghaie, R. Sabet,
H. Fazeli and G. Bostaki, Eur. J. Med. Chem., 2009, 44, 2145.
7 (a) G. A. Burdock, M. Soni and I. G. Carabin, Regul. Toxicol.
Pharmacol., 2001, 33, 80; (b) J. M. Noh, S. Y. Kwak,
D. H. Kim and Y. S. Lee, Biopolymers, 2007, 88, 300.
8 J. Alverson, J. Invertebr. Pathol., 2003, 83, 60.
9 (a) Y. Higa, M. Kawawbe, K. Nabae, Y. Toda, S. Kitamoto and
T. Hara, J. Toxicol. Sci., 2007, 32, 143; (b) M. Yamato,
K. Hashigaki, Y. Yasumoto, J. Sakai, R. F. Luduena and
A. Banerjee, J. Med. Chem., 1987, 30, 1897.
based on test wells relative to control wells. The cell growth 10 X. Xiong and M. C. Pirrung, Org. Lett., 2008, 10, 1151.
¨
inhibition of compounds was analyzed by generating dose 11 M. D. Aytemir, E. Septioglu and U. Çalıs,
response curves as a plot of the percentage of surviving cells Arzneimittelforschung, 2010, 60, 22.
versus drug concentration. Anticancer activity of the cancer cells 12 (a) V. G. Yuen, P. Caravan, L. Gelmini, N. Glover,
to the test compounds was articulated in terms of IC50 value,
which denes as a concentration of compound resulting in the
reduction of absorbance to 50% with respect to controls.18
J. H. Mcneill, I. A. Setyawati, Y. Zhouand and C. J. Orvig,
J. Inorg. Biochem., 1997, 73, 109; (b) Y. Ohyamaand and
Y. Mishima, Fragrance J., 1990, 6, 53; (c) J. S. Chen,
C. I. Wei, R. S. Rolle, W. S. Otwell, M. O. Balaban and
M. R. Marshall, J. Agric. Food Chem., 1991, 39, 1396; (d)
H. Mitani, I. Koshiishi, T. Sumita and T. Imanari, Eur. J.
Pharmacol., 2001, 411, 169; (e) H. S. Rho, S. M. Ahn,
D. S. Yoo, M. K. Kim, D. H. Cho and J. Y. Cho, Bioorg. Med.
Chem. Lett., 2010, 20, 6569; (f) S. Y. Kwak, J. M. Noh,
S. H. Park, J. W. Byun, H. R. Choi, K. C. Rark and Y. S. Lee,
Bioorg. Med. Chem. Lett., 2010, 20, 738; (g) A. Shahrisa and
Z. Ghasemi, Chem. Heterocycl. Compd., 2010, 46, 37; (h)
B. V. S. Reddy, M. R. Reddy, G. Narasimhulu and
J. S. Yadav, Tetrahedron Lett., 2010, 51, 5677; (i)
J. H. Kasser, W. Kandioller, C. G. Hartinger, A. A. Nazarov,
V. B. Arion, P. J. Dyson and B. K. Keppler, J. Organomet.
Chem., 2010, 695, 875.
Acknowledgements
S. M. S. R. and M. S thanks to Council of Scientic and Indus-
trial Research, Government of India for the award of a fellow-
ship. Funding from the CSIR project, SMiLE is gratefully
acknowledged.
Notes and references
1 P. Perlmutter, Conjugate addition reactions in organic
synthesis, Pergamon: Oxford, UK, 1992.
2 For selected reviews of asymmetric Michael additions see: (a)
B.-L. Li, Y.-F. Wang, S.-P. Luo, A.-G. Zhong, Z.-B. Li, X.-H. Du
and D.-Q. Xu, Eur. J. Org. Chem., 2010, 656; (b) J.-R. Chen,
Y.-J. Cao, Y.-Q. Zhou, F. Tan, L. Fu, X.-Y. Zhu and
W.-J. Xiao, Org. Biomol. Chem., 2010, 8, 1275; (c) X.-Y. Cao,
J.-C. Zheng, Y.-X. Li, Z.-C. Shu, X.-L. Sun, B.-Q. Wang and
Y. Tang, Tetrahedron, 2010, 66, 9703; (d) C. Yu, Y. Zhang,
A. Song, Y. Ji and W. Wang, Chem. – Eur. J., 2011, 17, 770;
(e) Y. Zhang and W. Wang, Catal. Sci. Technol., 2012, 2, 42.
3 (a) O. N. Garcia and R. Alonso, Org. Biomol. Chem., 2013, 11,
512; (b) H. Ishikawa, M. Honma and Y. Hayashi, Angew.
Chem., Int. Ed., 2011, 50, 2824.
13 (a) P. A. Wender, N. D. Angelo, V. I. Elitzin, M. Ernst,
E. E. J. Ugueto, J. A. Kowalski, S. McKendry, M. Rehfeuter
and R. Sun, Org. Lett., 2007, 9, 1829; (b) P. A. Wender and
J. L. Mascarenas, Tetrahedron Lett., 1992, 33, 2115; (c)
P. A. Wender and J. L. Mascarenas, J. Org. Chem., 1991, 56,
6267; (d) P. A. Wender and F. E. McDonald, J. Am. Chem.
Soc., 1990, 112, 4956.
14 (a) A. A. Shestopalov, L. A. Rodinovskaya, A. M. Shestopalov
and V. P. Litvinov, Russ. Chem. Bull., 2004, 53, 724; (b)
M.-Z. Piao and K. Imafuku, Tetrahedron Lett., 1997, 38, 5301.
15 J. Wang, Q. Zhang, H. Zhang, Y. Feng, W. Yuana and
X. Zhang, Org. Biomol. Chem., 2012, 10, 2950.
4 (a) B. Vakulya, S. Varga, A. Csampai and T. Soos, Org. Lett.,
´
2005, 7, 1967; (b) B. Vakulya, S. Varga and T. Soos, J. Org.
16 (a) R. P. Cheng, S. H. Gellman and W. F. DeGrado, Chem.
Rev., 2001, 101, 3219; (b) D. Seebach, A. K. Beck,
S. Capone, G. Deniau, U. Groselj and E. Zass, Synthesis,
2009, 1; (c) D. Seebach and J. Gardiner, Acc. Chem. Res.,
2008, 41, 1366; (d) G. Lelais and D. Seebach, Biopolymers,
2004, 76, 206.
17 M. A. Reddy, N. Jain, D. Yada, C. Kishore, J. R. Vangala,
P. R. Surendra, A. Addlagatta, S. V. Kalivendi and
B. Sreedhar, J. Med. Chem., 2011, 54, 6751.
Chem., 2008, 73, 3475; (c) S. J. Connon, Chem. Commun.,
2008, 2499; (d) C. Curti, G. Rassu, V. Zambrano, L. Pinna,
G. Pelosi, A. Sartori, L. Battistini, F. Zanardi and
G. Casiraghi, Angew. Chem., Int. Ed., 2012, 51, 6200.
5 (a) S. Kong, W. Fan, G. Wu and Z. Miao, Angew. Chem., Int.
Ed., 2012, 51, 8864; (b) B. V. S. Reddy, S. M. Reddy and
M. Swain, RSC Adv., 2013, 3, 930.
´
´
6 (a) J. Brtko, L. Rondahl, M. Fickova, D. Hudecova, V. Eybl and
M. Uher, Cent. Eur. J. Public Health, 2004, 12, 8; (b)
¨
18 A. S. Kumar, M. A. Reddy, N. Jain, C. Kishor, T. R. Murthy,
D. Ramesh, B. Supriya, A. Addlagatta, S. V. Kalivendi and
B. Sreedhar, Eur. J. Med. Chem., 2013, 60, 305.
M. D. Aytemir, D. D. Erol, R. C. Hider and M. Ozalp, Turk.
J. Chem., 2003, 27, 757; (c) M. D. Aytemir, R. C. Hider,
D. D. Erol, M. Ozalp and M. Ekizoglu, Turk. J. Chem., 2003,
¨
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9107–9111 | 9111