Phytochemical Investigation of Iphiona aucheri. Structural Revision of Donine

Article abstract of DOI:10.1007/s10600-019-02842-0

Investigation of an extract of Iphiona aucheri afforded compounds 1–3. These compounds were identified by detailed spectroscopic and spectrometric analysis, however, a literature search revealed that NMR and mass data similar to those of compound 3 have been reported for donine alkaloid 4. Investigation of the experimental and calculated NMR data of compound 4 revealed that the proposed structure should be revised to 3. This was further confirmed by synthesis of compounds 3 and 4.

Full text of DOI:10.1007/s10600-019-02842-0

DOI 10.1007/s10600-019-02842-0
Chemistry of Natural Compounds, Vol. 55, No. 5, September, 2019
PHYTOCHEMICAL INVESTIGATION OF Iphiona aucheri.
STRUCTURAL REVISION OF DONINE
1*
2
Yousef Dashti, Christian Hobson,
1
Fatemeh Mazraati Tajabadi,
and Hassan Rezadoost
3
Investigation of an extract of Iphiona aucheri afforded compounds 1–3. These compounds were identified
by detailed spectroscopic and spectrometric analysis, however, a literature search revealed that NMR and
mass data similar to those of compound 3 have been reported for donine alkaloid 4. Investigation of the
experimental and calculated NMR data of compound 4 revealed that the proposed structure should be revised
to 3. This was further confirmed by synthesis of compounds 3 and 4.
Keywords: Iphiona aucheri, donine, GIAO-NMR calculation, structure revision.
Iphiona aucheri belongs to the family Compositae and is distributed in Iran, the Arabian Peninsula, and North-East
Africa [1]. The plant has been reported to be toxic to animals [2]. Previous phytochemical investigations of this species
resulted in the identification of different secondary metabolites including the pyrrolizidine alkaloid isotussilagine and several
terpenoids including the diterpenoids atractyloside and carboxyatractyloside [3]. The latest metabolite, carboxyatractyloside,
was identified to be responsible for the plant toxicity [3]. In this study, investigation of the extract of I. aucheri resulted in the
identification of compounds 1–3. The mass and NMR data of compound 1 were identical to the reported values of dimethyl
(methylenedi-4,1-phenylene)biscarbamate which has been purified from Magnolia kachirachirai and Cortex Mori [4–6].
Compounds 2 and 3 were identified as analogues of compound 1; however, we noticed that NMR data similar to those of
compound 3 have been reported for the alkaloid donine (4) with a different structure [7]. Alkaloid 4 has been identified from
Arundo donax [7], and there is no other report on the isolation of donine or related alkaloids from any other natural sources.
A close investigation of the data reported for compound 4 revealed that the structure of the metabolite was misassigned and
should be revised to compound 3.
1''
1'
1
3'
O
3
O
O
O
O
N
H
N
H
O
7'
7
O
N
H
N
H
O
9
5'
5
1
2
H
N
H
N
O
O
O
O
O
N
H
N
O
H
O
O
4
3
COSY
HMBC
NOESY
1) Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111 Australia, e-mail:
dashti.yousef@gmail.com; 2) Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK; 3) Department of
Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113, Tehran,
Iran. Published in Khimiya Prirodnykh Soedinenii, No. 5, September–October, 2019, pp. 776–780. Original article submitted
September 21, 2018.
902
0009-3130/19/5505-0902 ©2019 Springer Science+Business Media, LLC

Compound 1 is symmetrical and shows only four proton and seven carbon chemical shifts. The LR-ESI-MS of
compound 2 showed a 14 Da mass difference from that of compound 1. A molecular formula of C H O N was established
18 20
4 2
for compound 2 by analysis of HR-ESI-MS and NMR data, establishing that 2 differed from compound 1 by a methylene.
Comparative analysis of the NMR data of compounds 1 and 2 showed that 2 was nonsymmetrical and possessed an additional
methyl (δ 15.2, δ 1.18), a methylene (δ 61.1, δ 4.25), and a quaternary carbon signal at δ 155.2 in the NMR spectra of
C
H
C
H
C
compound 2. Investigation of the COSY and HMBC correlations showed that an ethoxy group replaced one of the methoxy
groups of compound 1. One side of the unsymmetrical molecule 2 showed HMBC correlation between the protons of methyl
(H-8′) at δ 3.74 and the carbonyl C-7′ at δ 155.6, while the other side showed correlation between the methylene protons of the
ethyl group (H-8) at δ 4.25 and the quaternary carbon of carbonyl C-7 at δ 155.2. The unsymmetrical character of the compound
was obvious in the splitting pattern of the aromatic protons as well. While the aromatic protons of the symmetric molecule 1
showed two doublets, compound 2 showed two unresolved methene doublets at δ 7.29 and 7.87.
H
+
The HR-ESI-MS analysis of compound 3 showed a mass at m/z 365.1468 [M + Na] corresponding to the cationized
molecule with the molecular formula C H O N Na (calcd 365.1471). The mass difference of 14 Da from compound 2
19 22
4 2
1
13
indicated the addition of a CH unit in compound 3. The H and C NMR spectroscopic data revealed that the molecule is
symmetric. The C NMR spectrum (pyridine-d ) of compound 3 in conjunction with the HSQC showed eight carbon signals,
2
13
5
including one methyl at δ 15.2, two methylenes at δ 41.3 and 61.2, two methines at δ 119.8 and 130.2, and three quaternary
1
carbons at δ 136.7, 139.0, and 155.2. The H NMR spectroscopic data (pyridine-d ) displayed five signals corresponding to a
5
triplet methyl at δ 1.18 (J = 7.1 Hz), a quartet methylene at δ 4.25 (J = 7.1 Hz), one singlet methylene at δ 3.93, and two
aromatic protons at δ 7.29 (d, J = 8.4 Hz) and 7.89 (d, J = 8.4 Hz). The COSY correlation indicated an ethoxy moiety and a
2
para-substituted benzene ring. The HMBC experiment revealed a J correlation from proton H -1′′ at δ 3.93 to the quaternary
2
3
carbon C-1, 1′ at δ 136.7 and J correlation to C-2, 6, 2′, 6′ at δ 130.2 ppm, indicating the direct connection of the methylene
at the center of the molecule to the benzene ring. Protons H-2, 6, 2′, 6′ at δ 7.29 ppm showed J correlations to C-1′′ at δ 41.3
and C-4, 4′ at δ 139.0, as well as J correlations to C-3, 5, 3′, 5′ at δ 119.8 ppm. The HMBC correlation between the NH
C
3
2
protons at δ 10.57 to C-3, 5, 3′, 5′ revealed that NH is connected to the quaternary carbons C-4, 4′. The NOESY correlations
between H -1′′ and H-2, 6, 2′, 6′ as well as NH and H-3, 5, 3′, 5′ also confirmed that NH is between benzene rings and carbonyl
2
1
groups. All data indicated that compound 3 is an analog of compounds 1 and 2; however, it was noted that the H and
C NMR values obtained for compound 3 are very similar to those reported for the donine alkaloid (4) isolated from the plant
13
Arundo donax [7]. The structure of donine had been assigned as a symmetric compound with two para-substituted benzene
rings and two ethyl ester groups on two sides of the compound with a methylene group at the center of the molecule. The
difference between donine and compound 3 is the position of the NH groups in the structure. While two NH groups in
compound 3 are positioned between benzene rings and the carbonyl groups to form carbamate, in donine they are placed
between benzene rings and the methylene group at the center of the molecule. The similarities between our NMR data for
compound 3 and reported values for compound 4 prompted us to investigate the reported structure.
The structure of 4 had been assigned mostly based on one-dimensional NMR data and mass spectrometry results.
The authors reported ten carbon signals instead of eight. Two additional signals had been identified as possible alternative
signals for the methine carbons of the benzene rings (Table 1). A close investigation of the reported carbon chemical shifts
identified three carbon resonances of the deuterated pyridine, which has been used as NMR solvent at δ 123.4, 135.5 and
C
149.8 with about 0.5 ppm downfield shift due to incorrect referencing. Excluding the solvent′s carbon chemical shifts, seven
carbons remained. Although not all of the carbon resonances of compound 4 have been annotated to their carbon, a comparative
analysis of the remaining seven carbon resonances of compound 4 to that of compounds 3 revealed a 0.5 ppm downfield shift
of the carbons of compound 3 compare to the molecule 4 (Table 1). The carbon that was not reported by the previous researchers
is a quaternary carbon at δ 136.7 (C-1, 1′) of compound 3.
The chemical shift reported for the carbonyl of compound 4 (δ 154.7) is too upfield for an ester group. This shift in
the carbon signal had been wrongly correlated to the inductive effect of the nitrogen atom in the para position of the benzene
ring, while the carbonyl carbon in a similar scaffold such as ethyl 4-aminobenzoate resonates at 166.9 ppm (CDCl ) [8]. The
3
reported chemical shift is more consistent for a carbamate. For instance, in compound 1 the carbon of carbonyl resonates at
δ 155.6 ppm (in both CDCl and pyridine-d ) and that in 2-[4′-[ethylcarbamoyl)phenyl]-N-acetylglycine resonates at δ 154.3
3
5
ppm (DMSO-d ) [4, 9]. The reported value for the carbon of the methylene (δ 40.8) at the center of compound 4 is also more
6
consistent with the values reported for the compounds with methylene directly attached to the benzene ring. Two examples are
molecule 1 (δ 41.2, pyridine-d ) and bis-(4-octanoylphenyl)methane (δ 41.8, CDCl ) [4, 10]. If the methylene is connected
C
6
C
3
from both sides to the nitrogen attached to a benzene ring, the carbon resonates more than 10 ppm downfield [11, 12].
903

TABLE 1. Comparison of the δ Chemical Shifts for Isolated and Synthesized Compound 3 and Also Reported Resonances
C
for Donine (4) and Synthesized Compound 4 (pyridine-d , δ, ppm)
5
C atom
Isolated
Synthesized
Reported *
Synthesized
4
3
3
4
41.3
136.7
130.2
119.8
139.0
155.2
61.2
41.3
136.7
130.3
119.8
139.0
155.2
61.2
40.8
53.3
152.9
112.8
132.4
119.5
167.3
60.7
1′′
Not reported/identified
′
1, 1
2, 6, 2′, 6′
129.7**
119.3**
138.5
154.7
60.6
′
′
3, 5, 3 , 5
4, 4′
7, 7′
8, 8′
9, 9′
15.2
15.2
14.7
15.0
______
*The extra carbon resonances of 123.4, 135.5, and 149.8 ppm belonging to the deuterated pyridine were also reported for
donine. **These resonances as well as the resonances at 123.4 and 135.5 ppm were reported as “possible alternative assignment
of the signals” of the carbon on the benzene ring of the donine.
130.2
128.0
136.7
135.9
41.3
41.2
119.8
115.5
154.7
165.1
H
N
H
N
40.8
54.6
61.2
61.5
O
O
O
O
15.2
13.6
O
N
H
N
H
O
O
O
139.0
135.5
155.2
151.6
3
4
13
Fig. 1. Comparison of the experimental and calculated C NMR chemical shifts of compound 3 and the
reported structure 4. Calculated chemical shifts are underlined.
In addition, the proton resonance of the methylene at the center of the donine structure was reported as a singlet at 3.89 ppm
(compound 3 shows a singlet at 3.93 ppm). Considering the fact that in the proposed structure of donine this methylene is
directly attached to the NH and pyridine-d has been used as NMR solvent, which is not a suitable solvent for proton-deuterium
5
exchange, the methylene should appear as a doublet instead of a singlet.
This finding was also supported by GIAO-NMR calculation of the correct 3 and incorrect 4 structures. The method
developed by Tantillo and co-workers was used for NMR calculation [13]. Following conformational searches, the low-energy
13
conformers were optimized at the B3LYP/6-31+G(d,p) level in pyridine using the PCM model. Then the C NMR chemical
shifts of the low-energy conformers (19 conformers for compound 3 and 31 conformers for compound 4) with Boltzmann
populations greater than 1% were calculated at the mPW1PW91/6-311+G(2d,p) level in pyridine using the PCM model. The
calculated carbon chemical shifts of compound 3 were very close to the experimental values (Fig. 1).
Since the experimental carbon chemical shifts of compound 4 had not been clearly annotated to their corresponding
carbon atoms [7], comparison of the experimental and calculated chemical shifts is unreliable. However, the carbon chemical
shifts of the methylene at the center of the molecule (40.8 ppm) and the quaternary carbon of the carbonyl (154.7 ppm) are
identifiable. As expected, the calculated carbon chemical shifts of these two carbons in 4 showed more than a 10 ppm downfield
shift compared to the experimental values. Except for the close values for the ethoxy group, no other correlations were found
between the calculated and the experimental carbon chemical shifts of compound 4.
Compounds 3 and 4 were then synthesized using one-step literature procedures (Scheme 1) [14, 15], and the carbon
chemical shifts of the synthetic compounds were compared to the values obtained for the isolated compound 3 and reported
values for compound 4 (Table 1). This comparison clarified the identical chemical shifts for the synthesized and isolated
compound 3, while the carbon chemical shifts of the synthesized compound 4 were different from the values reported for
donine 4. All this information revealed that the reported structure for alkaloid 4 is not correct, and therefore the structure of
donine should be revised to compound 3.
904

O
O
a
H N
2
NH
2
O
N
H
N
H
O
3
H
N
H
NH
N
2
b
O
O
O
O
4
O
O
a. Ethyl chloroformate, Et N, DCM; b. CH O, EtOH
3
2
Scheme 1. Procedures used for synthesis of compounds 3 and 4.
a
O
O
TEA
NMP
O
O
OH
C
C
O
+
HO
N
N
N
H
N
H
O
n
Polyurethane
b
O
O
O
O
O
MeOH
N
H
N
H
O
O
N
N
H
O
H
n
Scheme 2. a) synthesis of polyurethane; b) possible degradation by methanol. TEA – triethylamine,
NMP – N-methylpyrrolidinone.
Compounds 1–3 have an unusual structural backbone that is not common in natural products; therefore, we sought to
investigate if they are real natural products or are contaminations of extraction process. Specifically, we suspected that these
compounds might be plasticizers as a plastic bucket was used for extraction. As shown in Scheme 2, polyurethane, which is a
component of many plastics, under exposure to methanol or ethanol might undergo methanolysis or ethanolysis to yield
compounds 1 and 3, respectively, and a mixture of methanol and ethanol might yield compound 2. We thus collected Iphiona
aucheri again from the same place at the same time of the year as it was previously collected. An extraction was performed
under previous conditions, but this time in a glass container instead of a plastic bucket. Upon investigation of the extract with
LC-MS, none of these compounds were detected. As we did not have access to the plastic container that was used for extraction,
we synthesized the polyurethane polymer based on a reported procedure [16] and then exposed it to methanol and ethanol
separately. Analysis by LC-MS after 1, 3, and 7 days did not show the target mass for compounds 1 and 3. Based on these data,
it was not possible to conclude whether compounds 1–3 are secondary metabolites produced by plants or extraction artifact,
and therefore more investigation needs to be performed to clarify whether these type of compounds are genuine natural
products or plasticizers.
In conclusion, three compounds were purified from extract of Iphiona aucheri. The structures of the compounds were
assigned by analysis of 1 and 2 D NMR and HR-ESI-MS data. It was noticed that mass and NMR data similar to those of
compound 3 have been reported for donine alkaloid 4 isolated from Arundo donax. Reinvestigation of the NMR data reported
for donine, GIAO-NMR calculations, and also synthesis of 3 and 4 revealed that the structure of donine should be
revised to 3.
EXPERIMENTAL
General Procedure. UV spectra were acquired on a Jasco V650 UV/vis spectrophotometer. Infrared spectra were
obtained on a FT-IR JASCO A-302 spectrophotometer in CHCl solvent. One- and two-dimensional NMR spectra were
3
1
13
recorded on a Varian spectrometer operating at 500 ( H NMR) and 125 ( C NMR) MHz. A Waters ZQ electrospray mass
spectrometer with a Phenomenex Luna C column (4.6 × 50 mm, 3 μm) was used for LC-MS analysis. A Betasil C column
18
18
(21.2 × 150 mm) was used for semipreparative HPLC separation. All HPLC and LC-MS experiments were performed with
905

MeOH–H O gradient solvent system. Silica gel mesh size 70–230 (E. Merck) was used for column chromatography.
2
Precoated silica gel plates (DC-Alugram 60 UV254, E. Merck) were utilized for thin-layer chromatography (TLC), and detection
was performed under UV (254 nm) and cerium(IV) sulfate spray reagent.
Extraction and Isolation. Aerial parts of I. aucheri were collected from Karri Village in Bushehr Province, Iran.
The plant material was air-dried under the shed and powdered. About 2 kg of the powdered material was extracted with 80%
EtOH (3 × 4.5 L) overnight at room temperature. After filtration, the extract was concentrated by rotary evaporation to yield
160 g crude extract. The crude extract was then fractionated by vacuum liquid chromatography (VLC) using silica gel as
stationary phase and eluted with stepwise-gradient solvents hexane, hexane–CHCl , CHCl –MeOH, and MeOH to give 12
3
3
main fractions. The polarity was first increased by 10%, then by 20% from 60% CHCl –hexane, to 20% MeOH–CHCl
3
3
followed by 50:50 MeOH–CHCl , and then finished by 100% MeOH. Subsequently, fraction 10 (60 mg) obtained from 20%
3
MeOH–CHCl was subjected to silica gel column chromatography with hexane–acetone as solvent system (from 5% to 50%
3
acetone–hexane), resulting in nine subfractions.
Subfraction 2 (18 mg) was then chromatographed by HPLC using a semipreparative reversed-phase C Betasil
18
column (21.2 mm × 150 mm). Initially isocratic conditions of 10% MeOH were used for 10 min, then a linear gradient from
10 to 100% MeOH was performed over 40 min and continued isocratically for 10 min at a flow rate of 9 mL/min.
Sixty fractions were collected in 1 min increments over 60 min. Compound 1 (4 mg) eluted in fraction 31, 2 (6 mg) in fractions
32 and 33, and 3 (5 mg) in fraction 34.
–1
Ethyl Methyl (Methylenedi-4,1-phenylene)biscarbamate (2). White amorphous solid. IR (CHCl , λ , cm ):
3
max
1
3298, 2926, 1715, 1603, 1531, 1227, 1070. UV (MeOH, λ , nm) (log ε): 206 (4.42), 246 (4.36). H NMR (500 MHz,
max
pyridine-d , δ, ppm, J/Hz): 1.18 (3H, t, J = 7.1, H-9), 3.74 (3H, s, H-8′), 3.93 (2H, s, H-1′′), 4.25 (2H, q, J = 7.1, H-8), 7.29
5
13
(4H, dd, J = 8.5, 1.9, H-2, 6, 2′, 6′), 7.87 (4H, t, J = 8.5, H-3, 5, 3′, 5′), 10.56 (NH), 10.65 (NH). C NMR (125 MHz,
pyridine-d , δ, ppm): 15.2 (C-9), 41.3 (C-1′′), 52.3 (C-8′), 61.1 (C-8), 119.8 (C-3, 5, 3′, 5′), 130.2 (C-2, 6, 2′, 6′), 136.6 (C-1, 1′),
5
+
139.0 (C-4, 4′), 155.2 (C-7), 155.6 (C-7′). HR-ESI-MS m/z 351.1315 [M + Na] (calcd for C H O N Na, 351.1315).
Diethyl (Methylenedi-4,1-phenylene)biscarbamate (3). White amorphous solid. IR (CHCl , λ , cm ): 3296,
2926, 1712, 1600, 1531, 1226, 1068. UV (MeOH, λ , nm) (log ε): 206 (4.47), 246 (4.45). H NMR (500 MHz, pyridine-d ,
18 20
4 2
–1
3
max
1
max
5
δ, ppm, J/Hz): 1.18 (6H, t, J = 7.1, H-9, 9′), 3.93 (2H, s, H-1′′), 4.25 (4H, q, J = 7.1, H-8, 8′), 7.29 (4H, d, J = 8.4, H-2, 6, 2′, 6′),
13
7.89 (4H, d, J = 8.4, H-3, 5, 3′, 5′), 10.57 (NH). C NMR (125 MHz, pyridine-d , δ, ppm): 15.2 (C-9, 9′), 41.3 (C-1′′), 61.2
5
(C-8, 8′), 119.8 (C-3, 5, 3′, 5′), 130.2 (C-2, 6, 2′, 6′), 136.7 (C-1, 1′), 139.0 (C-4, 4′), 155.2 (C-7, 7′). HR-ESI-MS m/z
+
365.1468 [M + Na] (calcd for C H O N Na, 365.1471).
19 22
4 2
1
Synthesized Diethyl 4,4′-(Methylenebis(azanediyl))-dibenzoate (4). White amorphous solid. H NMR (500 MHz,
DMSO-d , δ, ppm, J/Hz): 1.26 (6H, t, J = 7, H-9, 9′), 4.20 (4H, q, J = 7, H-8, 8′), 4.57 (2H, t, J = 5.5, H-1′′), 6.72 (4H, d,
6
13
J = 8.5, H-2, 6, 2′, 6′), 7.25 (2H, t, J = 5.5, NH), 7.70 (4H, d, J = 8.5, H-3, 5, 3′, 5′). C NMR (125 MHz, DMSO-d , δ, ppm):
6
14.3 (C-9, 9′), 51.2 (C-1′′), 59.6 (C-8, 8′), 111.6 (C-2, 6, 2′, 6′), 117.0 (C-4, 4′), 130.8 (C-3, 5, 3′, 5′), 151.6 (C-1, 1′), 165.8
1
(C-7, 7′). H NMR (500 MHz, pyridine-d , δ, ppm, J/Hz): 1.22 (6H, t, J = 7, H-9, 9′), 4.32 (4H, q, J = 7, H-8, 8′), 4.97 (2H, t,
5
13
J = 5.5, H-1′′), 7.02 (4H, d, J = 8.5, H-2, 6, 2′, 6′), 7.87 (2H, t, J = 5.5, NH), 8.15 (4H, d, J = 8.5, H-3, 5, 3′, 5′). C NMR
(125 MHz, pyridine-d , δ, ppm): 15.0 (C-9, 9′), 53.3 (C-1′′), 60.7 (C-8, 8′), 112.8 (C-2, 6, 2′, 6′), 119.5 (C-4, 4′), 132.4 (C-3,
5
+
5, 3′, 5′), 152.9 (C-1, 1′), 167.3 (C-7, 7′). HR-ESI-MS m/z 365.1471 [M + Na] (calcd for C H O N Na, 365.1472).
19 22
4 2
Computational Methods. Conformational searches were performed in Schrodinger MacroModel 9.1 using the OPLS
2005 (Optimized Potential for Liquid Simulations) force field in H O. Gaussian 09 was used for optimization and NMR
2
calculations. Conformers occurring within a 2 kcal/mol energy window from the global minimum were chosen for geometrical
optimization with the B3LYPfunctional and the 6-31+G(d,p) basis set in the gas-phase with the Gaussian 09 program. Vibrational
analysis was done at the same level to confirm minima, and frequency lists were checked to ensure that no imaginary frequencies
were present. The NMR calculations were performed in Gaussian 09 using the gauge-independent atomic orbitals (GIAO)
method and SCRF-mPW1PW91/6-311+G(2d,p) level of theory in pyridine as solvent. The calculated NMR isotopic shifts
were empirically scaled according to the following formula:
δ = (b – σ)/–m,
where δ is the calculated chemical shift referenced to the TMS, b is the y-intercept, σ is the calculated isotopic chemical
13
shielding value, and m is the slope. The scaling factors used for C shifts were m = –1.0533 and b = 186.5242, obtained from
the CHESHIRE CCAT website (http://cheshirenmr.info/). The calculated chemical shifts were obtained from the
Boltzmann-averaged chemical shift of all the conformers.
906

REFERENCES
1.
2.
3.
4.
5.
6.
A. Anderberg, Nord. J. Bot., 5, 169 (1985).
U. Wernery, E. Roder, A. Billah, and M. Ali, Tierarztl Umsch, 47, 196 (1992).
E. Roeder, T. Bourauel, U. Meier, and H. Wiedenfeld, Phytochemistry, 37, 353 (1994).
H. S. Chang, M. J. Cheng, and I. S. Chen, Helv. Chim. Acta, 94, 703 (2011).
Q. Yang, A. Robertson, and H. Alper, Org. Lett., 10, 5079 (2008).
L. Feng, Y-h. Xu, S-s. Wang, W. Au-yeung, Z-g. Zheng, R-s. Wang, Q. Zhu, and P. Xiang, Phytother. Res., 26,
412 (2012).
7.
8.
V. U. Khuzhaev, S. F. Aripova, and U. A. Abdullaev, Chem. Nat. Compd., 32, 194 (1996).
B. K. Banik, I. Banik, and F. F. Becker, Indium/Ammonium Chloride-Mediated Selective Reduction of Aromatic Nitro
Compounds: Ethyl 4-aminobenzoate, in: Organic Syntheses, John Wiley & Sons, Inc., 2003.
C. Suparpprom and T. Vilaivan, J. Nat. Prod., 64, 1114 (2001).
Z-M. Lu, Q-J. Zhang, R-Y. Chen, and D-Q. Yu, Chin. J. Nat. Med., 9, 90 (2011).
S. J. Rochfort, S. Moore, C. Craft, N. H. Martin, R. M. Van Wagoner, and J. L. C. Wright, J. Nat. Prod.,
72, 1773 (2009).
9.
10.
11.
12.
13.
X-H. Cai, H. Jiang, Y. Li, G-G. Cheng, Y-P. Liu, T. Feng, and X-D. Luo, Chin. J. Nat. Med., 9, 259 (2011).
M. W. Lodewyk, C. Soldi, P. B. Jones, M. M. Olmstead, J. Rita, J. T. Shaw, and D. J. Tantillo, J. Am. Chem. Soc.,
134, 18550 (2012).
14.
15.
16.
W. S. Murphy and K. P. Raman, J. Chem. Soc., Perkin Trans. 1, 447 (1981).
D-H. Bae and H. J. Shine, J. Org. Chem., 45, 4448 (1980).
Y. Nagase, M. Oku, K. Ishihara, and Y. Iwasaki, European Pat. No. EP1528063A1 (2004).
907