Synthesis and antifungal activity of carabrone derivatives

Article abstract of DOI:10.3390/molecules15096485

Nine derivatives 6-14 of carabrone (1) were synthesized and tested in vitro against Colletotrichum lagenarium Ell et Halst using the spore germination method. Among all of the derivatives, compounds 6-8 and 12 showed more potent antifungal activity than 1

Full text of DOI:10.3390/molecules15096485

Molecules 2010, 15, 6485-6492; doi:10.3390/molecules15096485
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Synthesis and Antifungal Activity of Carabrone Derivatives
Jun-Tao Feng 1,*, Zhi-Qing Ma 1, Jiang-Hua Li 1, Jun He 1, Hui Xu 1,2,* and Xing Zhang 1
1
Research and Development Center of Biorational Pesticide, College of Plant Protection, Northwest
A&F University, Yangling 712100, China
2
Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F
University,Yangling 712100, China
* Author to whom correspondence should be addressed; E-Mails: fengjt67@hotmail.com (J.-T.F.);
orgxuhui@nwsuaf.edu.cn (H.X.)
Received: 6 July 2010; in revised form: 11 August 2010 / Accepted: 23 August 2010 /
Published: 16 September 2010
Abstract: Nine derivatives 6-14 of carabrone (1) were synthesized and tested in vitro
against Colletotrichum lagenarium Ell et Halst using the spore germination method.
Among all of the derivatives, compounds 6-8 and 12 showed more potent antifungal
activity than 1. Structure-activity relationships (SAR) demonstrated that the γ-lactone was
necessary for the antifungal activity of 1, and the substituents on the C-4 position of 1
could significantly affect the antifungal activity.
Keywords: carabrone; structural modification; synthesis; antifungal activity
1. Introduction
Carabrone (1, Figure 1), containing cyclopropane and sesquiterpene lactone moieties, was first
isolated from the fruits of Carpesium abrotanoides [1], and is widely distributed in feverfew and other
plant species [2-9]. It was demonstrated that compound 1 displays cytotoxic [10], antibacterial [11,12],
and antitumor activity [13]. In our course of screening for novel naturally occurring phytofungicides
from the plants in northwestern China, compound 1 was obtained from Carpesium macrocephalum,
and exhibited antifungal activities in vitro and in vivo against Botrytis cinerea, Colletotrichum
lagenarium, and Erysiphe graminis [14]. Subsequently, we prepared four derivatives (2-5, Figure 1)
from 1, and found that the 11,13-double bond and the carbonyl group on the C-4 position of 1 are two

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active sites [15,16]. In order to further investigate the effect of lactone and substituents on the C-4
position of 1 on the antifungal activity, herein we synthesized nine new carabrone derivatives 6-14 as
potential antifungal agents.
Figure 1. The chemical structures of carabrone and its derivatives.
14
O
9
8
O
O 12
O
2
O
10
O
11
1
3
5
OH
CH2OCH3
7
6
OH
O
4
O
3
13
2
1
15
O
O
O
O
5
4
2. Results and Discussion
Nine carabrone derivatives 6-14 were synthesized as shown in Scheme 1. Compound 6 was
prepared by the reaction of 2,4-dinitrophenyl hydrazine (DNPH) and 1 in the presence of hydrogen
chloride (HCl). Benzhydrazide or semicarbazide reacted with 1 to give compounds 7 and 8,
respectively. Compound 9 was prepared from 1 with dry HCl. Compound 10 was synthesized by the
reduction of the carbonyl group of 1 in the presence of NaBH4, followed by chlorination of the 4-OH
group of 2 with thionyl chloride (SOCl2). Compound 2 reacted with acyl chlorides in the presence of
pyridine to afford compounds 11-14. All compounds were characterized by 1H-NMR, IR, and HR-MS
spectra.
Scheme 1. The synthetic route to carabrone derivatives 6-14.
O
O
O
O
NNH
NNH
COPh
NO
2
7
NO
6
2
benzhydrazide
60%
O
86%
DNPH
O
O
O
RCOCl/Py/DCM
56-73%
semicarbazide
84%
NaBH
MeOH
4
OCOR
R
1
2
11-14
NNH
CONH
R
2
HCl/MeOH
53%
SOCl /DCM
2
11 CH=CH 13 (CH ) Me
2
2 4
8
73%
12 i-Pr
14 Ph
O
O
Cl
CO Me
2
Cl
O
10
9

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The antifungal activity was assayed in vitro against Colletotrichum lagenarium Ell et Halst by the
spore germination method. Chlorothalonil was used as a positive control. As described in Table 1,
compounds 6-8 exhibited the most potent antifungal activity with the EC50 values of 2.24, 4.32 and
3.03 μg/mL, respectively, i.e., the antifungal activity of 6, 7 and 8 was 1.5-3 times more potent than
that of 1. However, the antifungal activity of other compounds was 1-8 times less than that of 1.
Obviously, substituents on the C-4 position of 1 could significantly affect the antifungal activity. For
example, introducing the hydrazone substituents on the C-4 position of 1 lead to the most potent
compounds (e.g., 6-8), while when other substituents, such as the hydroxy group, chloro atom, and
ester groups (except isobutyryloxy group), were introduced on the C-4 position of 1, the corresponding
compounds showed the less potent activity than 1 (e.g., 10, 11, 13 and 14). Interestingly, when the
isobutyryloxy group was introduced on the C-4 position of 1 to give 12, the EC50 value of 12 was
6.39 μg/mL, which was more potent than that of 1. Meanwhile, compound 1 was nearly eightfold more
potent than 9 (EC50 7.10 μg/mL for 1 vs. EC50 56.30 μg/mL for 9). This demonstrated that the γ-
lactone was necessary for the antifungal activity of 1, and opening the lactone would lead to a less
potent compound (1 vs. 9).
Table 1. Inhibition rates of carabrone derivates (6-14) against spore germination of
Colletotrichum lagenarium. a
Regression equation
Compd.
r
EC50b (μg/mL)
EC50 95% CL/(μg/mL)
(Y = a + bX)
1
6
0.9974
0.9923
0.9817
0.9979
0.9942
0.9969
0.9882
0.9920
0.9970
0.9962
0.9935
7.10
2.24
6.19～8.02
1.97～2.55
Y = 3.6090 + 1.6337X
Y = 4.5130 + 1.3891X
Y = 3.4038 + 2.5118X
Y = 4.3577 + 1.3351X
Y = 3.1867 + 1.0358X
Y = 3.2442 + 1.1736X
Y = 4.2780 + 0.6720X
Y = 4.3568 + 0.7209X
Y = 3.7775 + 0.9365X
Y = 3.7676 + 1.0011X
Y = 5.1247 + 1.0081X
7
8
9
10
11
12
13
14
4.32
3.03
3.81～4.85
2.58～3.55
56.30
31.34
10.78
6.39
20.20
17.02
0.75
42.95～73.80
26.08～37.66
9.16～12.68
5.33～7.65
16.85～24.22
14.41～20.11
0.63～0.90
chlorothalonil c
a
b
Values are means of three separate experiments;
EC50 (50% effective concentration),
c
concentration of compound that reduces spore germination by 50%; Chlorothalonil was used as a
positive control.
3. Experimental
3.1. General
All the solvents were of analytical grade and the reagents were commercially available. Thin-layer
chromatography (TLC) and silica gel-column chromatography were performed with silica gel plates
using silica gel 60 GF254, and 200-300 mesh (Qingdao Haiyang Chemical Co., Ltd., China). Melting
points were determined on a digital melting-point apparatus and uncorrected. All compounds were
characterized by proton nuclear magnetic resonance (1H-NMR), high-resolution mass spectra (HR-
MS), mass spectra (MS-ESI), and infrared spectra (IR), respectively.

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3.2. Synthesis
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-keto 2, 4-dinitrophenyl hydrazone-butyl)-5a-methyl-3-methylene-3a, 4,
4a, 5, 6, 6a-hexahydrocyclopropa[f]benzofuran-2-one (6). A mixture of compound 1 (124 mg,
0.5 mmol), 2,4-dinitrophenyl hydrazine (DNPH, 39.6 mg, 2 mmol) and hydrochloric acid (0.2 mL,
6 mol/L) in anhydrous methanol (MeOH, 10 mL) was reacted at 60 ºC until a precipitate formed. The
reaction mixture was then filtered, and the filtrate was evaporated under educed pressure. The residue
was recrystallized in dimethyl sulfoxide (DMSO) to produce 6 as a yellow solid. Yield: 86%, m.p.
1
181–182 ºC [17]; IR (KBr) cm-1: 3321, 2956, 1756, 1593, 1530, 1345; H-NMR (400 MHz, CDCl3)
δ: 10.79 (s, 1H, =NNH), 8.84 (m, 1H, H-3´), 8.35 (d, J = 6.8 Hz, 1H, H-5´), 7.82 (d, J = 10.0 Hz, 1H,
H-6´), 5.99 (d, J = 2.4 Hz, 1H, H-13), 5.62 (d, J = 2.4 Hz, 1H, H-13), 4.80 (m, 1H, H-8), 3.31 (m, 2H),
3.18 (m, 1H, H-7), 2.43~2.55 (m, 1H), 2.26~2.35 (m, 1H), 2.05 (s, 3H, H-15), 1.54~1.64 (m, 2H), 1.05
(s, 3H, H-14), 0.85~0.91 (m, 2H), 0.53 (m, 1H, H-5), 0.35 (m, 1H, H-1); HR-MS (ESI): m/z calcd for
C21H25N4O6 ([M+H]+), 429.1769; found, 429.1763.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-keto benzoyl hydrazone-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6,
6a-hexahydrocyclopropa[f]benzofuran-2-one (7). A mixture of 1 (125 mg, 0.5 mmol), benzhydrazide
(82 mg, 0.6 mmol), and 1-2 drops of HOAc in absolute ethanol (10 mL) was stirred at 80 ºC. After 3 h,
the solvent was removed under reduced pressure to give a residue, which was dissolved in CH2Cl2.
Then the organic phase was washed with H2O, dried by anhydrous Na2SO4, and evaporated under
reduced pressure. Finally, the residue was purified by silica gel-column chromatography using
1
CH2Cl2-EtOAc as the eluent to give 7 as a pale yellow solid. Yield: 60%, m.p. 45–46 ºC; H-NMR
(500 MHz, CDCl3) δ: 8.77 (s, 1H, CONH), 7.79 (s, 2H, Ar-H), 7.46 (s, 1H, Ar-H), 7.42 (s, 2H, Ar-H),
6.19-6.20 (m, 1H, H-13), 5.22 (d, J = 2.2 Hz, 1H, H-13), 4.72-4.4.77 (m, 1H, H-8), 3.11-3.13 (m, 1H,
H-7), 2.48-2.51 (m, 2H), 2.26-2.33 (m, 3H), 2.21 (s, 1H), 1.94 (s, 2H), 1.51-1.73 (m, 2H), 1.23 (s, 1H),
1.06 (s, 3H, H-14), 0.83-0.97 (m, 2H, H-2). MS (ESI): m/z 389 ([M+Na]+), 100).
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-keto carbamoyl hydrazone-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6,
6a-hexahydrocyclopropa[f]benzofuran-2-one (8). A mixture of 1 (223.2 mg, 0.9 mmol), semicarbazide
hydrochloride (111.5 mg, 1 mmol) and sodium acetate (176.8 mg, 1.3 mmol) in distilled H2O (5 mL)
was stirred at 60 ºC until a white precipitate was produced, then the reaction mixture was filtered, and
the filtrate was evaporated under reduced pressure. The residue was recrystallized from distilled H2O-
MeOH to give 8 as a white solid. Yield: 84%, m.p. 171–173 ºC; IR (KBr) cm-1: 3317, 2963, 1753,
1690, 1620; 1H-NMR (400 MHz, CDCl3) δ: 6.14 (d, J = 2.6 Hz, 1H, H-13), 5.64 (d,
J = 2.4 Hz, 1H, H-13), 4.88 (m, 1H, H-8), 4.78 (s, 1H, =NNH), 4.60 (s, 2H, O=CNH2), 3.36 (m, 2H),
3.20 (m, 1H, H-7), 2.24~2.27 (m, 1H), 1.97~2.13 (m, 1H), 1.85 (s, 3H, H-15), 1.81~1.84 (m, 1H),
1.43~1.51 (m, 1H), 1.04 (s, 3H, H-14), 0.85~0.92 (m, 2H), 0.53 (m, 1H, H-5), 0.38 (m, 1H, H-1);
HR-MS (ESI): m/z calcd for C16H24N3O3 ([M+H]+), 306.1812; found, 306.1812.
4-oxo-7β-(2-methylformate) propene-8-chloro-carabrane (9) [18]. Compound 1 (248 mg, 1 mmol)
was dissolved in anhydrous MeOH (40 mL) under reflux, and a flow of dry HCl was passed for 6 h.
When the starting material was nearly complete as checked by TLC, the reaction mixture was cooled
to room temperature. Sodium bicarbonate (NaHCO3, 20 mg) and distilled H2O (30 mL) were added to

Molecules 2010, 15
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the above mixture, which was extracted with CH2Cl2 (50 mL × 3). The organic phases were combined,
and washed with 2% aq. NaHCO3, and distilled H2O, dried over anhydrous Na2SO4, and evaporated
under reduced pressure. Finally, the residue was purified by silica gel-column chromatography using
18
petroleum ether-EtOAc as the eluent to give 9 as a colorless oily liquid. Yield: 53%, [α]D +49.7 (C
1
0.35, CHCl3); IR (KBr) cm-1 2942, 1756, 1695, 1632; H-NMR (400 MHz, CDCl3) δ: 6.13 (d,
J = 2.6 Hz, 1H, H-13), 5.58 (d, J = 2.4 Hz, 1H, H-13), 3.85 (m, 1H, H-8), 3.76 (s, 3H, OCH3), 3.31 (m,
2H), 2.82 (m, 1H, H-7), 2.26~2.13 (m, 2H), 1.94 (s, 3H, H-15), 1.58~1.63 (m, 2H), 1.16 (s, 3H, H-14),
0.86~0.93 (m, 2H), 0.54 (m, 1H, H-5), 0.32 (m, 1H, H-1); HR-MS (ESI): m/z calcd for C16H27NO3Cl
([M+NH4 ]+), 316.1697; found, 316.1695.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-chloro-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6, 6a-
hexahydrocyclopropa[f]benzofuran-2-one (10) [19]. A mixture of 2 (100 mg, 0.4 mmol) and pyridine
(0.1 mL) in anhydrous CH2Cl2 (15 mL) was stirred at 0 ºC. Thionyl chloride (SOCl2, 0.1 mL) was
added dropwise. After the addition was complete, the mixture was stirred under reflux. When the
starting material was nearly completely consumed, as checked by TLC, NaHCO3 (20 mg) and distilled
H2O (10 mL) were added to the above mixture, which was extracted with CH2Cl2 (20 mL × 3). The
organic phases were combined, washed with 0.3% HCl, saturated aq. Na2CO3 and brine, dried over
anhydrous Na2SO4, and evaporated under reduced pressure. Finally, the residue was purified by silica
gel-column chromatography using petroleum ether-EtOAc as the eluent to produce 10 as colorless
1
acicular crystals. Yield: 73%, m.p. 97–99 ºC; IR (KBr) cm-1: 2943, 1757, 1625, 1148, 628; H NMR
(400 MHz, CDCl3) δ: 6.24 (d, J = 2.6 Hz, 1H, H-13), 5.56 (d, J = 2.4 Hz, 1H, H-13), 4.81 (m, 1H, H-
8), 4.04 (m, 1H, H-4), 3.14 (m, 1H, H-7), 2.17~2.37 (m, 2H, H-3), 1.79~1.83 (m, 2H), 1.56 (d,
J = 6.0 Hz, 3H, H-15), 1.43~1.46 (m, 2H), 1.09 (s, 3H, H-14), 0.88~0.95 (m, 2H), 0.47 (m, 1H, H-5),
0.38 (m, 1H, H-1); HR-MS (ESI): m/z calcd for C15H25NO2Cl ([M+NH4 ]+), 286.1568; found,
286.1565.
General procedure for the synthesis of compounds 11-14 [20]
A mixture of 2 (100 mg, 0.4 mmol) and pyridine (0.1 mL) in anhydrous CH2Cl2 (15 mL) was stirred
at 0 ºC. Acyl chloride (0.1 mL) in anhydrous CH2Cl2 (2 mL) was added dropwise. After the addition,
the mixture was stirred under reflux. When the reaction was nearly complete, as checked by TLC,
NaHCO3 (20 mg) and distilled H2O (10 mL) were added to the above mixture, which was extracted
with CH2Cl2 (30 mL × 3). The organic phases were combined, washed by 0.3% HCl, saturated aq.
Na2CO3 and brine, and evaporated under the reduced pressure. Finally, the residue was purified by
silica gel column chromatography using petroleum ether-acetone as the eluent to give compounds 11-14.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-vinylCarbonate-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6, 6a-
18
hexahydrocyclopropa[f]benzofuran-2-one (11). Yield: 73%, a colorless oily liquid; [α]D +58.7 (C
1
0.47, CHCl3); IR (KBr) cm-1: 2977, 1757, 1715, 1642, 1203; H-NMR (400 MHz, CDCl3) δ: 6.40 (d,
J = 16.8 Hz, 1H, CH=CH2), 6.23 (d, J = 2.8 Hz, 1H, H-13), 6.10 (m, 1H, CH=CH2), 5.82 (d,
J =10.8 Hz, 1H, CH=CH2), 5.56 (d, J =2.4 Hz, 1H, H-13), 4.99 (m, 1H, H-8), 4.78 (m, 1H, H-4), 3.16
(m, 1H, H-7), 2.31~2.39 (m, 2H), 1.59~1.62 (m, 2H), 1.36~1.45 (m, 2H), 1.27 (d, J =6.0 Hz, 3H, H-

Molecules 2010, 15
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15), 1.06 (s, 3H, H-14), 0.85~0.99 (m, 2H), 0.43 (m, 1H, H-5), 0.35 (m, 1H, H-1); HR-MS (ESI): m/z
calcd for C18H28NO4 ([M+NH4 ]+), 322.2013; found, 322.2008.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-isopropylCarbonate-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6, 6a-
18
hexahydrocyclopropa[f]benzofuran-2-one (12). Yield: 72%; a colorless oily liquid; [α]D +36.4 (C
1
0.41, CHCl3); IR (KBr) cm-1: 2974, 1757, 1722, 1660, 1148; H-NMR (400 MHz, CDCl3) δ: 6.23 (d,
J = 2.6 Hz, 1H, H-13), 5.56 (d, J = 2.4 Hz, 1H, H-13), 4.95 (m, 1H, H-8), 4.80 (m, 1H, H-4), 3.16 (m,
1H, H-7), 2.51 (m, 1H, CH(CH3)2), 2.30~2.38 (m, 2H), 1.59~1.61 (m, 2H), 1.35~1.44 (m, 2H), 1.23 (d,
J = 6.0 Hz, 3H, H-15), 1.18 (d, J = 10.8 Hz, 3H, CHCH3), 1.14 (d, J = 11.2 Hz, 3H, CHCH3), 1.07 (s,
3H, H-14), 0.87~0.98 (m, 2H), 0.43 (m, 1H, H-5), 0.34 (m, 1H, H-1); HR-MS (ESI): m/z calcd for
C19H28O4Na ([M+Na]+), 343.1880; found, 343.1875.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-pentylCarbonate-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6, 6a-
18
hexahydrocyclopropa[f]benzofuran-2-one (13). Yield: 70%; a colorless oily liquid; [α]D +49.4 (C
1
0.52, CHCl3); IR (KBr) cm-1: 2935, 1722, 1660, 1146; H-NMR (400 MHz, CDCl3) δ: 6.23 (d,
J = 2.6 Hz, 1H, H-13), 5.56 (d, J = 2.4 Hz, 1H, H-13), 4.95 (m, 1H, H-8), 4.78 (m, 1H, H-4), 3.16 (m,
1H, H-7), 3.01~3.04 (m, 1H, O=CCH2), 2.51~2.54 (m, 1H, O=CCH2), 2.30~2.38 (m, 2H), 1.59~1.61
(m, 2H), 1.27~1.51 (m, 8H), 1.23 (d, J = 6.0 Hz, 3H, H-15), 1.06 (s, 3H, H-14), 0.90~0.99 (m, 2H),
0.86~0.89 (m, 3H, CH2CH3), 0.43 (m, 1H, H-5), 0.35 (m, 1H, H-1); HR-MS (ESI): m/z calcd for
C21H36NO4 ([M+NH4]+), 366.2639; found, 366.2632.
(3aR, 4aS, 5S, 5aR, 6aR)-5-(3-phenylCarbonate-butyl)-5a-methyl-3-methylene-3a, 4, 4a, 5, 6, 6a-
18
hexahydrocyclopropa[f]benzofuran-2-one (14). Yield: 56%; a colorless oily liquid; [α]D +73.9 (C
1
0.31, CHCl3); IR (KBr) cm-1: 2942, 1757, 1711, 1485, 715; H-NMR (400 MHz, CDCl3) δ: 8.03 (m,
2H, H-3´, 5´), 7.57 (m, 1H, H-4´), 7.46 (m, 2H, H-2´, 6´), 6.24 (d, J = 2.6 Hz, 1H, H-13), 5.55 (d,
J = 2.4 Hz, 1H, H-13), 5.18 (m, 1H, H-8), 4.77 (m, 1H, H-4), 3.15 (m, 1H, H-7), 2.28~2.36 (m, 2H),
1.63~1.79 (m, 2H), 1.42~1.56 (m, 2H), 1.23 (d, J = 6.0 Hz, 3H, H-15), 1.08 (s, 3H, H-14), 0.88~0.92
(m, 2H), 0.47 (m, 1H, H-5), 0.35 (m, 1H, H-1); HR-MS (ESI): m/z calcd for C22H30NO4 ([M+NH4]+),
372.2169; found, 372.2168.
3.3. Spore Germination Assay
Microorganisms and maintenance: the strain of Colletotrichum lagenarium (36199) was provided
by Agricultural Culture Collection of China and maintained on potato dextrose agar (PDA).
Compounds 1 and 6-14 were dissolved in acetone or DMSO and added to 2% water agar medium after
sterilization to produce concentrations of 100, 75, 50, 25, 10, and 5 µg/mL or 10, 5, 2, 1, 0.5 and 0.25
µg/mL of medium. Conidial suspensions (0.2 mL) containing 1 × 105 condia/mL, derived from
cultures grown for 12 d on PDA plates, were spread on 2% water agar. Conidia were allowed to
germinate 25 ± 1 ºC for 8 h. Germination was quantified at three sites by counting 100 conidia per site.
A conidium was scored as germinated if the germ tube had reached at least half the length of the
conidium. Three plates for each concentration were used and the experiment was performed thrice,
along with 98% chlorothalonil (Syngenta Crop Protection Co., Ltd., China) as a positive control. The

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EC50 for inhibition of spore germination was calculated for each isolate. Analysis of parameters was
made with the statistical analysis system (SAS institute, Inc., Cary, NC, USA) [21].
4. Conclusions
In summary, nine new carabrone derivatives were synthesized and evaluated in vitro against
Colletotrichum lagenarium Ell et Halst. Compounds 6-8, and 12 displayed the more potent antifungal
activity than 1. Meanwhile, the structure-activity relationship (SAR) demonstrated that a γ-lactone
moiety was necessary for the antifungal activity of 1, and the substituents on the C-4 position of 1
could significantly affect their antifungal activity, e.g., introduction of the hydrazone substituents on
the C-4 position of 1 lead to more potent compounds.
Acknowledgements
This work was supported by a grant from the National Natural Science Foundation of China (grant
No. 30971934) and the National Department Public Benefit Research Foundation of China (grant No.
200903052). We are deeply grateful for kind and helpful advice given by Tian Xuan, during the
spectroscopic analysis of these compounds.
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Sample Availability: Samples of the compounds are available from the authors.
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