Solvent-free synthesis of novel spirocyclic oxindole derivatives via a Michael-aldol cascade by grinding

Article abstract of DOI:10.3184/174751918X15260499526233

A simple and novel synthesis of spirocyclic oxindole derivatives by the reaction of (E)-3-arylideneindole-2-ones and 1,4-dithiane-2,5-diol via a Michael-aldol cascade under solvent-free reaction conditions is reported. This method provides a new practical and facile approach to 4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-thiophen]-2-ones in moderate to good yields. The structures of all the products were characterised by NMR, infrared spectroscopy and HRMS.

Full text of DOI:10.3184/174751918X15260499526233

244 RESEARCH PAPER
VOL. 42 MAY, 244–246
JOURNAL OF CHEMICAL RESEARCH 2018
Solvent-free synthesis of novel spirocyclic oxindole derivatives via a
Michael-aldol cascade by grinding
Renzhi Liu, Qihong Mei, Yan Shen, Yiqiang Wu and Wenlin Xie*
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Key Laboratory of Theoretical Organic Chemistry and Functional
Molecules, Ministry of Education, Hunan Provincal Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Xiangtan, Hunan
411201, P.R. China
A simple and novel synthesis of spirocyclic oxindole derivatives by the reaction of (E)-3-arylideneindole-2-ones and 1,4-dithiane-2,5-diol
via a Michael-aldol cascade under solvent-free reaction conditions is reported. This method provides a new practical and facile approach
to 4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-thiophen]-2-ones in moderate to good yields. The structures of all the products
were characterised by NMR, infrared spectroscopy and HRMS.
Keywords: oxindole, spirocycle, Michael-aldol cascade, solvent free synthesis
The oxindole moiety is an important structure responsible
for the biological activity of alkaloids and pharmaceutically
active compounds, such as pteropodine,1 paraherquamide A,2
tryprostatins B3 and sunitinib.4 Compounds with an oxindole
unit have aroused great interest because of their broad spectrum
of biological activities, such as antitumour,5 anti-inflammatory,
analgesic,6 cyclooxygenase7 and myosin inhibition8 activity.
Spiroheterocycles are important structures found in many
biologically active natural products9 and their biological
properties make them good targets for drug candidates and
clinical pharmaceuticals.10,11
It is well known that there are pronounced advantages
to solvent-free synthetic approaches, including easy work-
up procedures, short reaction times and simple apparatus
requirements, which has attracted considerable attention in
recent years.12–14 Here we report a facile synthesis of spirocyclic
oxindole derivatives by the Michael-aldol cascade reaction of
1,4-dithiane-2,5-diol with (E)-3-arylideneindole-2-ones under
solvent-free conditions (Scheme 1).
The structures of all compounds 2a–j were established by
different spectroscopic techniques (NMR, IR) and HRMS.
The high-resolution mass spectrum of 2d gave the molecular
ion peak at m/z 332.0515, which indicates the addition of one
molecule of 1,4-dithiane-2,5-diol to 1d. The IR spectrum of
2d displayed νC=O at 1689.4 cm−1. The 1H NMR spectrum of 2d
revealed a doublet at δ 5.58 ppm (J = 6.0 Hz, OH), two singlets
— a singlet at δ 10.40 ppm for –NH and another singlet at δ 4.94
resulting from –HCPh — a multiplet at δ 4.70–4.65 ppm for –
CH–OH, a doublet of doublets at δ 3.32 ppm (J1 = 10.0 Hz, J2 =
6.0 Hz) and a triplet at δ 3.20 ppm (J = 10.0 Hz) resulting from
H2C5′, The presence of signals at δ 6.62–7.58 ppm corresponded
to the aromatic protons.
The 13C NMR spectrum of the product 2d exhibited the
presence of carbonyl carbons at δ 176.79 (C2). The signal at
δ 79.45 represented the spiro carbon of C3. Furthermore, the
structure of the product was confirmed by X-ray diffraction
analysis of 2d (Fig. 1).
There are three diastereoisomeric carbon atoms in the
products 2a–j; therefore, two diastereoisomers might exist in
1
Results and discussion
the obtained products. TLC and the H NMR spectra of the
The
4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-
reaction mixtures only showed one set of typical absorptions
for the characteristic groups in the molecules, which indicated
that the products 2a–j existed as only one diastereoisomer with
the structure being established via the single-crystal structure
determination.
thio-phen]-2-ones 2 were synthesised in moderate to good yields
by the Michael-aldol cascade reaction of (E)-3-arylideneindole-
2-ones with 1,4-dithiane-2,5-diol in the presence of triethylamine
under solvent-free conditions at room temperature. The reaction
can be scaled up to 5 mmol with similar yields, for example, 5
mmol of 1a gives 1.17 g of 2a (79.0% yield) under the reaction
conditions. The intermediate product (E)-3-arylideneindole-2-
ones 1 were obtained by condensation of oxindole and various
substituted benzaldehydes in the presence of triethylamine at
room temperature.
R
R
S
HO
S
S
Et3N, RT
OH
+
O
solvent-free, grinding
N
H
OH
O
N
H
1a-j
2a-j
2a: R = H, 2b: R = o-Cl, 2c: R = m-Cl, 2d: R = p-Cl, 2e: R = p-CH3, 2f: R = m-CH3,
2g: R = p-CH3O, 2h: R = o-Br, 2i: R = o-F, 2j: R = p-F
Fig. 1 ORTEP diagram of 2d with 50% probability.
Scheme 1 Synthesis of spiro oxindole-tetrahydrothiophenes.
* Correspondent. E-mail: xwl2000zsu@163.com

JOURNAL OF CHEMICAL RESEARCH 2018 245
Conclusion
4′-Hydroxy-2′-(3-chlorophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2c): White powder; yield 71.7%; m.p.
176–177 °C; IR (KBr) (ν cm−1): 3434, 3292, 3014, 2920, 1699, 1618,
1469, 1398, 1087; 1H NMR (500 MHz, DMSO): δ 10.45 (s, 1H,
NH), 7.57 (d, J = 7.5 Hz, 1H, ArH), 7.15–7.07 (m, 5H, ArH), 6.97 (t,
J = 7.5 Hz, 1H, ArH), 6.63 (d, J = 7.5 Hz, 1H, ArH), 5.61 (d, J = 6.0
Hz, 1H, OH), 4.94 (s, 1H, CH), 4.70–4.66 (m, 1H, CH–OH), 3.32 (dd,
J = 10.0, 6.0 Hz, 1H, CH2), 3.21 (t, J = 10.0 Hz, 1H, CH2); 13C NMR
(125 MHz, DMSO): δ 176.77, 142.28, 138.33, 132.32, 129.56, 128.16,
127.88, 127.60, 126.81, 126.42, 125.16, 121.06, 109.24, 79.40, 65.14,
52.02, 34.22. HRMS (ESI) m/z calcd for [C17H15ClNO2S]+ (M + H)+:
332.0507; found: 332.0502.
4′-Hydroxy-2′-(4-chlorophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2d): White powder; yield 81.3%; m.p.
176–177 °C; IR (KBr) (ν cm−1): 3294, 3019, 2926, 1689, 1619, 1467,
1399, 1326, 1171, 1082, 1017; 1H NMR (500 MHz, DMSO): δ 10.40 (s,
1H, NH), 7.57 (d, J = 7.0 Hz, 1H, ArH), 7.17–7.13 (m, 4H, ArH), 7.09 (t,
J = 7.5 Hz, 1H, ArH), 6.96 (t, J = 7.5 Hz, 1H, ArH), 6.62 (d, J = 8.0 Hz,
1H, ArH), 5.58 (d, J = 6.0 Hz, 1H, OH), 4.94 (s, 1H, CH), 4.70–4.65
(m, 1H, CH–OH), 3.32 (dd, J = 10.0, 6.0 Hz, 1H, CH2), 3.20 (t, J = 10.0
Hz, 1H, CH2); 13C NMR (125 MHz, DMSO): δ 176.79, 142.30, 134.81,
132.09, 129.84, 128.10, 127.70, 126.40, 125.24, 121.09, 109.19, 79.45,
65.15, 52.00, 34.20. HRMS (ESI) m/z calcd for [C17H15ClNO2S]+ (M +
H)+: 332.0507; found: 332.0515.
4′-Hydroxy-2′-(4-methylphenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2e): White powder; yield 89.5%; m.p.
185–186 °C; IR (KBr) (ν cm−1): 3294, 3012, 2930, 1691, 1619, 1469,
1395, 1329, 1174, 1078; 1H NMR (500 MHz, DMSO): δ 10.33 (s, 1H,
NH), 7.60 (d, J = 7.0 Hz, 1H, ArH), 7.08 (t, J = 7.5 Hz, 1H, ArH),
7.01 (d, J = 8.0 Hz, 2H, ArH), 6.96 (t, J = 7.5 Hz, 1H, ArH), 6.87 (d,
J = 8.0 Hz, 2H, ArH), 6.61 (d, J = 7.5 Hz, 1H, ArH), 5.53 (d, J = 5.5
Hz, 1H, OH), 4.91 (s, 1H, CH), 4.69–4.64 (m, 1H, CH–OH), 3.30 (dd,
J = 10.0, 7.5 Hz, 1H, CH2), 3.17 (t, J = 10.0 Hz, 1H, CH2); 13C NMR
(125 MHz, DMSO): δ 176.98, 142.37, 136.71, 132.63, 128.29, 128.04,
127.90, 126.46, 125.63, 120.97, 109.09, 79.54, 65.12, 52.50, 34.04,
20.47. HRMS (ESI) m/z calcd for [C18H18NO2S]+ (M + H)+: 312.1053;
found: 312.1055.
A facile and green synthesis of spiro compounds was
accomplished by the Michael-aldol cascade of (E)-3-
arylideneindole-2-one and 1,4-dithiane-2,5-diol under solvent-
free reaction conditions. Simplicity of operation, high yields
and easy work-up are the key advantages of this method.
Experimental
Compound 1 ((E)-3-arylideneindole-2-ones) was prepared according
to the literature method.15 All of the reagents were from commercial
suppliers and used without further purification. All of the solvents
were freshly distilled from the appropriate drying agents before use.
The analytical TLCs were performed with silica gel 60 F254 plates.
Column chromatography was carried out by using silica gel 60
(200–300 mesh). All NMR spectra were recorded on a Bruker AV-II
1
500 MHz NMR spectrometer, operating at 500 MHz for H, and 125
MHz for 13C. TMS was used as an internal reference for H and 13C
1
chemical shifts and CDCl3 was used as solvent. Mass spectra were
collected on a Waters Xevo Q-TOF HRMS instrument. IR spectra were
recorded on a PerkinElmer spectrometer (Spectrum One). Melting
points were measured with a Yanaco MP500 melting point apparatus
and are uncorrected. X-ray analysis was performed on a Bruker
Apex-II CCD diffractometer. A single crystal of 2d was obtained by
slow evaporation of a CH2Cl2/CH3OH solution of 2d. Crystal data for
2d: C17H14ClNO2S, Mr = 331.80 g mol1, triclinic space group P21/c,
a = 13.6768(16) Å, b = 12.4921(15)Å, c = 8.9120(11) Å, β = 104.395(4),
V = 1474.8(3) Å3, T = 296(2) K, Z = 4, Dc = 1.494 g m–3, μ = 0.407 mm–1,
F(000) = 688, Rint = 0.0467, 9048 reflections, 2588 with I > 2σ(I) for
200 parameters, GOF = 1.068, R1 = 0.0338, wR2 = 0.0908 [I > 2σ(I)]
and R1 =0.0387, wR2 = 0.0960 (all data). CCDC 1814629 contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of 4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2); general procedure
(E)-3-arylideneindole-2-ones 1 (1.0 mmol) and 1,4-dithiane-2,5-
diol (1.0 mmol) was added into a mortar containing the triethylamine
(3 mmol). The resulting reaction mixture was ground at room
temperature. After completion of the reaction as monitored by TLC,
the mixture was purified by column chromatography on silica gel
using petroleum ether and ethyl acetate (3:1, V/V) as eluent and
recrystallised from ethyl alcohol to afford the corresponding product 2.
4′-Hydroxy-2′-phenyl-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-
thiophen]-2-ones (2a): White powder; yield 82.3%; m.p. 181–182 °C;
IR (KBr) (ν cm−1): 3458, 3183, 3060, 2939, 2888, 1687, 1621, 1469,
1404, 1345, 1188, 1089; 1H NMR (500 MHz, DMSO): δ 10.38 (s, 1H,
NH), 7.60 (d, J = 7.5 Hz, 1H, ArH), 7.15–7.13 (m, 2H, ArH), 7.08–7.06
(m, 4H, ArH), 6.96 (t, J = 7.5 Hz, 1H, ArH), 6.60 (d, J = 7.5 Hz, 1H,
ArH), 5.58 (d, J = 5.0 Hz, 1H, OH), 4.96 (s, 1H, CH), 4.71–4.67 (m,
1H, CH–OH), 3.32 (dd, J = 10.5, 7.5 Hz, 1H, CH2), 3.20 (t, J = 10.0
Hz, 1H, CH2); 13C NMR (125 MHz, DMSO): δ 176.96, 142.32, 135.68,
128.11, 127.93, 127.68, 127.57, 126.46, 125.53, 120.99, 109.08, 79.54,
65.14, 52.69, 34.08. HRMS (ESI) m/z calcd for [C17H16NO2S]+ (M +
H)+: 298.0896; found: 298.0905.
4′-Hydroxy-2′-(3-methylphenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2f): White powder; yield 87.8%; m.p.
174–175 °C; IR (KBr) (ν cm−1): 3422, 3221, 2929, 3015, 1704, 1617,
1
1466, 1402, 1328, 1094; H NMR (500 MHz, DMSO): δ 10.37 (s,
1H, NH), 7.60 (d, J = 7.5 Hz, 1H, ArH), 7.08 (t, J = 7.5 Hz, 1H, ArH),
6.98–6.87 (m, 5H, ArH), 6.61 (d, J = 7.5 Hz, 1H, ArH), 5.56 (d, J = 6.0
Hz, 1H, OH), 4.90 (s, 1H, CH), 4.69–4.65 (m, 1H, CH-OH), 3.31 (dd,
J = 10.0, 7.5 Hz, 1H, CH2), 3.18 (t, J = 10.0 Hz, 1H, CH2); 13C NMR
(125 MHz, DMSO): δ 176.99, 142.35, 136.61, 135.62, 128.88, 128.22,
127.90, 127.52, 126.52, 125.61, 125.26, 120.88, 109.09, 79.55, 65.09,
52.66, 34.06, 20.84. HRMS (ESI) m/z calcd for [C18H18NO2S]+ (M +
H)+: 312.1053; found: 312.1062.
4 ′- Hydrox y-2 ′- (4 - methox yphenyl) - 4 ′, 5′- dihydro -2 ′ H-
spiro[oxindole-3,3′-thiophen]-2-ones (2g): Yellow powder; yield
61.3%; m.p. 196–197 °C; IR (KBr) (ν cm−1): 3391, 3225, 3016, 2932,
1704, 1510, 1401, 1248, 1176, 1060, 1028; 1H NMR (500 MHz,
DMSO): δ 10.33 (s, 1H, NH), 7.61 (d, J = 7.5 Hz, 1H, ArH), 7.09 (t,
J = 7.0 Hz, 1H, ArH), 7.04 (d, J = 8.5 Hz, 2H, ArH), 6.97 (t, J = 7.5 Hz,
1H, ArH), 6.64–6.62 (m, 3H, ArH), 5.52 (d, J = 6.0 Hz, 1H, OH), 4.89
(s, 1H, CH), 4.68–4.63 (m, 1H, CH–OH), 3.60 (s, 3H, CH3), 3.30 (dd,
J = 10.5, 7.5 Hz, 1H, CH2), 3.17 (t, J = 10.0 Hz, 1H, CH2); 13C NMR
(125 MHz, DMSO): δ 176.98, 158.52, 142.40, 129.30, 127.90, 127.36,
126.48, 125.66, 120.98, 113.03, 109.10, 79.42, 65.16, 54.84, 52.29,
34.09. HRMS (ESI) m/z calcd for [C18H18NO3S]+ (M + H)+: 328.1002;
found: 328.1008.
4′-Hydroxy-2′-(2-chlorophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2b): White powder; yield 85.6%; m.p.
182–183 °C; IR (KBr) (ν cm−1): 3379, 3229, 3012, 2934, 1713, 1621,
1
1468, 1402, 1353, 1322, 1240, 1080; H NMR (500 MHz, DMSO): δ
10.34 (s, 1H, NH), 8.05 (d, J = 8.0 Hz, 1H, ArH), 7.40 (t, J = 7.5 Hz,
1H, ArH), 7.25–7.16 (m, 2H, ArH), 7.02 (t, J = 7.5 Hz, 1H, ArH), 6.69
(d, J = 7.5 Hz, 1H, ArH), 6.52 (t, J = 7.5 Hz, 1H, ArH), 6.00 (d, J = 7.5
Hz, 1H, ArH), 5.61 (d, J = 5.0 Hz, 1H, OH), 5.13 (s, 1H, CH), 4.51–4.47
(m, 1H, CH–OH), 3.48 (t, J = 10.0 Hz, 1H, CH2), 3.15 (dd, J = 10.0,
6.0 Hz, 1H, CH2); 13C NMR (125 MHz, DMSO): δ 178.09, 143.30,
136.90, 134.21, 131.42, 129.10, 128.83, 128.24, 127.79, 126.80, 124.00,
120.40, 108.69, 80.76, 61.53, 48.50, 33.37. HRMS (ESI) m/z calcd for
[C17H15ClNO2S]+ (M + H)+: 332.0507; found: 332.0512.
4′-Hydroxy-2′-(2-bromophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-
3,3′-thiophen]-2-ones (2h): White powder; yield 70.1%; m.p.
175–176 °C; IR (KBr) (ν cm−1): 3354, 3227, 3029, 2934, 1712, 1620,
1
1466, 1433, 1403, 1352, 1238, 1080; H NMR (500 MHz, DMSO): δ
10.34 (s, 1H, NH), 8.08 (d, J = 8.0 Hz, 1H, ArH), 7.45 (t, J = 7.5 Hz, 1H,
ArH), 7.35 (d, J = 8.0 Hz, 1H, ArH), 7.16 (t, J = 7.5 Hz, 1H, ArH), 7.02

246 JOURNAL OF CHEMICAL RESEARCH 2018
(t, J = 7.5 Hz, 1H, ArH), 6.68 (d, J = 8.0 Hz, 1H, ArH), 6.50 (t, J = 7.5 Hz,
1H, ArH), 5.91 (d, J = 7.5 Hz, 1H, ArH), 5.60 (d, J = 5.0 Hz, 1H, OH),
5.07 (s, 1H, CH), 4.53–4.49 (m, 1H, CH–OH), 3.48 (t, J = 10.0 Hz, 1H,
CH2), 3.15 (dd, J = 10.0, 6.0 Hz, 1H, CH2); 13C NMR (125 MHz, DMSO):
δ 177.97, 143.46, 138.67, 132.10, 131.90, 129.42, 128.15, 127.77, 127.36,
125.84, 123.99, 120.36, 108.69, 80.45, 61.54, 50.81, 33.12. HRMS (ESI)
m/z calcd for [C17H15BrNO2S]+ (M+H)+: 376.0001; found: 376.0009.
4′-Hydroxy-2′-(2-fluorophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-
thiophen]-2-ones (2i): White powder; yield 82.4%; m.p. 171–172 °C; IR
(KBr) (ν cm−1): 3266, 3011, 2930, 1696, 1618, 1470, 1400, 1330, 1225,
1178, 1089; 1H NMR (500 MHz, DMSO): δ 10.35 (s, 1H, NH), 7.51 (d,
J = 7.0 Hz, 1H, ArH), 7.45–7.42 (m, 1H, ArH), 7.10–7.07 (m, 2H, ArH),
6.98–6.92 (m, 2H, ArH), 6.87 (t, J = 7.5 Hz, 1H, ArH), 6.63 (d, J = 7.0 Hz,
1H, ArH), 5.62 (d, J = 5.5 Hz, 1H, OH), 5.24 (s, 1H, CH), 4.72–4.68 (m,
1H, CH–OH), 3.34 (dd, J = 10.0, 7.5 Hz, 1H, CH2), 3.25 (t, J = 10.0 Hz,
1H, CH2); 13C NMR (125 MHz, DMSO): δ 176.48, 159.86 (d, J = 245.0
Hz), 142.52, 130.89 (d, J = 2.5 Hz), 129.36 (d, J = 8.8 Hz), 128.08, 126.66,
125.43, 123.40 (d, J = 3.8 Hz), 123.02 (d, J = 13.8 Hz), 120.85, 114.68 (d, J
= 22.5 Hz), 109.09, 79.86, 63.85, 44.49, 34.40. HRMS (ESI) m/z calcd for
[C17H15FNO2S]+ (M + H)+: 316.0802; found: 316.0810.
4′-Hydroxy-2′-(4-fluorophenyl)-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-
thiophen]-2-ones (2j): Grey powder; yield 72.2%; m.p. 175–176 °C; IR
(KBr) (ν cm−1): 3304, 3012, 2916, 1691, 1619, 1508, 1468, 1397, 1225, 1168,
1080; 1H NMR (500 MHz, DMSO): δ 10.39 (s, 1H, NH), 7.59 (d, J = 7.0
Hz, 1H, ArH), 7.17–7.14 (m, 2H, ArH), 7.09 (t, J = 7.0 Hz, 1H, ArH), 6.97
(t, J = 7.5 Hz, 1H, ArH), 6.92 (t, J = 8.5 Hz, 2H, ArH), 6.62 (d, J = 7.5 Hz,
1H, ArH), 5.58 (d, J = 5.5 Hz, 1H, OH), 4.94 (s, 1H, CH), 4.70–4.66 (m,
1H, CH–OH), 3.32 (dd, J = 10.0, 7.5 Hz, 1H, CH2), 3.20 (t, J = 10.0 Hz,
1H, CH2); 13C NMR (125 MHz, DMSO): δ 176.84, 161.34 (d, J = 242.5
Hz), 142.33, 131.84 (d, J = 2.5 Hz), 129.99 (d, J = 8.8 Hz), 128.04, 126.44,
125.34, 121.05, 114.50 (d, J = 21.2 Hz), 109.15, 79.39, 65.20, 52.00, 34.22.
HRMS (ESI) m/z calcd for [C17H15FNO2S]+ (M + H)+: 316.0802; found:
316.0809.
Hunan Province (2015JJ4026) and the Scientific Research Fund
of Hunan Provincial Education Department (No. 17K032) for
financial support of this work.
Received 28 February 2018; accepted 19 April 2018
Paper 1805288
https://doi.org/10.3184/174751918X15260499526233
Published online: 30 May 2018
References
1
T.H. Kang, K. Matsumoto, Y. Murakami, H. Takayama, M. Kitajima, N. Aimi
and H. Watanabe, Eur. J. Pharmacol., 2002, 444, 39.
2
3
4
R.M. Williams and R.J. Cox, Acc. Chem. Res., 2003, 36, 127.
C.B. Cui, H. Kakeya and H. Osada., Tetrahedron, 1996, 52, 12651.
L. Sun, C. Liang, S. Shirazian, Y. Zhou, T. Miller, J. Cui, J.Y. Fukuda, J.Y. Chu,
A. Nematalla, X.Y. Wang, H. Chen, A. Sistla, T.C. Luu, F. Tang, J. Wei and C.
Tang, J. Med. Chem., 2003, 46, 1116.
5
D.B. Mendel, A.D. Laird, B.D. Smolich, R.A. Blake, C. Liang, A.L. Hannah,
R.M. Shaheen, L.M. Ellis, S. Weitman, L.K. Shawver and J.M. Cherrington,
Anticancer Drug Des., 2000, 15, 29.
6
7
L. Zhou, J.S. Yang, X. Wu, J.H. Zou, X.D. Xu and G.Z. Tu, Heterocycles, 2005,
65, 1409.
R.P. Robinson, L.A. Reiter, W.E. Barth, A.M. Campeta, K. Cooper, B.J.
Cronin, R. Destito, K.M. Donahue, F.C. Falkner, E.F. Fiese, D.L. Johnson, A.V.
Kuperman, T.E. Liston, D. Malloy, J.J. Martin, D.Y. Mitchell, F.W. Rusek, S.L.
Shamblin and C.F. Wright, J. Med. Chem., 1996, 39, 10.
8
9
C.C. Hughes, J.B. MacMillan, S.P. Gaudêncio, W. Fenical and J.J. LaClair,
Angew. Chem. Int. Ed., 2009, 48, 728.
B.M. Trost and M.K. Brennan, Synthesis, 2009, 18, 3003.
10 J. Orbe, J.A. Sanchez-Arias, O. Rabal, J.A. Rodriguez, A. Salicio, A. Ugarte, M.
Belzunce, M. Xu, W. Wu, H. Tan, H. Ma, J.A. Paramo and J. Oyarzabal, J. Med.
Chem., 2015, 58, 2465.
11 S. Emami and Z. Ghanbarimasir, Eur. J. Med. Chem., 2015, 93, 539.
12 S. Hirashima, T. Sakai and K. Nakashima, Tetrahedron Lett., 2014, 55, 4334.
13 W.L. Xie, G.W. Xiao and L.Q. Gu, Chin. J. Org. Chem., 2008, 28, 1123.
14 M. Pattarawarapan, S. Jaita and W. Phakhodee, Tetrahedron Lett., 2016,
57, 3171.
Acknowledgements
The authors thank the National Natural Science Foundation
of China (No. 21571058), the Natural Science Foundation of
15 X.F. Li, A.T. Zheng, B. Liu, X.Y. Yu and P.G. Yi, J. Heterocyclic Chem.,
2013, 50, 1198.