Structural Revision of Guttiferone F and 30-epi-Cambogin

Article abstract of DOI:10.1021/acs.jnatprod.0c01031

Guttiferone F, a natural polyprenylated polycyclic acylphloroglucinol, was originally assigned as the 30-epimer of garcinol by NMR data analyses. Conversion of guttiferone F in the presence of acid afforded its cyclized form (2a, which was previously assi

Full text of DOI:10.1021/acs.jnatprod.0c01031

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Structural Revision of Guttiferone F and 30-epi-Cambogin
Dan Zheng,# Jia-Ming Jiang,# Si-Min Chen, Shi-Jie Wan, Han-Gui Ren, Gan Chen, Gang Xu, Hua Zhou,
Hong Zhang,* and Hong-Xi Xu*
Cite This: J. Nat. Prod. 2021, 84, 1397−1402
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ABSTRACT: Guttiferone F, a natural polyprenylated polycyclic acylphlor-
oglucinol, was originally assigned as the 30-epimer of garcinol by NMR data
analyses. Conversion of guttiferone F in the presence of acid afforded its
cyclized form (2a), which was previously assigned as 30-epi-cambogin.
However, the absolute configurations of guttiferone F and 2a have not been
determined. Reinvestigation of the structures of those two compounds, using
X-ray and NMR data analyses and chemical transformation, revealed that the
original assignment of the C-30 absolute configuration in guttiferone F and 2a
should be inverted. Guttiferone F is indeed garcinol, and 2a, which was
previously identified as 30-epi-cambogin, is cambogin.
n 1999, Fuller and co-workers reported the isolation of a new
natural polyprenylated polycyclic acylphloroglucinol
guttiferone F and 2a due to their structural complexity and
instrumentation limitations previously. In the current study,
experimental and calculated ECD data were tentatively used to
determine the absolute configuration of 1. However, the
calculated ECD spectrum of both (1R,5R,7R,30S)-1 and
(1R,5R,7R,30R)-1 matched well with the experimental ECD
spectrum of 1 (Figure 1), which indicated that the ECD data
could not be used to determine the C-30 absolute configuration.
Since attempts to confirm the absolute configuration of 1 using
ECD data failed, attempts were made to obtain its crystals
suitable for X-ray diffraction analysis. Indeed, crystals of 1
(CDCC 2032861) were obtained by the slow evaporation of a
MeCN solution at room temperature. The X-ray diffraction
experiments with Cu Kα radiation not only permitted definition
of the 2D structure but also allowed the assignment of the
absolute configuration of 1 as (1R,5R,7R,30S) [Figure 2, Flack
parameter value 0.14(7)]. This result provided definitive
evidence for assigning the (30S) absolute configuration of 1,
which was in accordance with garcinol instead of 30-epi-garcinol.
Fuller et al.1 compared NMR spectra of guttiferone F in
methanol-d4 + 0.1% TFA with those of garcinol in CDCl3.16
Since the NMR solvent has a significant influence on the
chemical shift values, even for the same compound, their NMR
data cannot be simply used to determine the structure of
I
(PPAP), guttiferone F, from the root wood of Allanblackia
stuhlmannii. Its structure was identified as the C-30 epimer of
garcinol by extensive NMR data analyses and by treatment with
acid to afford its analogue (2a), previously assigned as 30-epi-
cambogin.1 These two compounds received a significant amount
of attention.2−12 In a recent investigation, guttiferone F was also
isolated from the twigs of Garcinia esculenta Y. H. Li.13 The
bioactive investigation revealed that guttiferone F induced HeLa
cell caspase 3-mediated apoptosis4 and prostate cancer cell
apoptosis under serum starvation via Ca2+ and c-Jun-N-terminal
kinase (JNK) elevation.14,15 An in vivo study showed that
guttiferone F significantly inhibited the growth of the xenograft
model using PC3 cells, combined with caloric restriction.14
These results suggested that guttiferone F is a potential
anticancer compound. However, the assignment of the absolute
configuration of guttiferone F is a challenging task due to its
structural complexity. Herein, we reinvestigated the absolute
configurations of guttiferone F and 2a using chemical trans-
formation and X-ray and NMR data analyses. These data
revealed that the original assignment of the C-30 absolute
configuration of guttiferone F and 2a should be inverted, and
their structures should be revised as garcinol and cambogin,
respectively. The HRMS, 1H and 13C NMR, and optical rotation
data of 1, reisolated from the twigs of G. esculenta, were highly
similar to those of guttiferone F1 (Table 1 and Experimental
Section). Its structure was originally assigned as the C-30 epimer
of garcinol based on its acid-catalyzed conversion to 2a
(Schemes 1 and 2).1 However, little evidence, except the
spectroscopic data comparison with garcinol and cambogin, was
presented to support the configurational assignments of
Received: September 23, 2020
Published: March 8, 2021
© 2021 American Chemical Society and
American Society of Pharmacognosy
https://dx.doi.org/10.1021/acs.jnatprod.0c01031
J. Nat. Prod. 2021, 84, 1397−1402
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Note
Table 1. 1H and 13C NMR Spectroscopic Data of Guttiferone
F, Garcinol, and 1
recorded in methanol-d4 + 0.1% TFA
recorded in CDCl3
garcinol
a
b
c
d
guttiferone F (ref)
1
(ref)
1
no.
δC
δH (J in Hz)
δC
δH (J in Hz)
δC
δC
1
2
3
4
5
6
7
8
69.4
69.8
69.9
69.9
193.7
117.9
196.1
59.7
50.2
47.9
194.3
118.0
196.3
60.0
50.4
48.1
195.2
116.0
194.0
58.1
42.7
47.0
194.5
116.0
194.1
58.0
42.7
47.0
1.49, m
2.24, d
(13.5)
1.48, m
2.25, d
(14.0)
43.8
43.9
49.8
49.7
2.04, dd
(13.5, 7.4)
2.05, m
9
210.6
195.5
129.5
210.8
195.6
129.7
207.1
199.1
127.8
116.6
143.9
149.9
114.4
120.2
209.4
198.6
128.1
116.5
143.8
149.9
114.4
120.3
10
11
12
13
14
15
16
117.3 7.19, d (2.0) 117.4 7.19, d (2.1)
146.3
152.5
115.0 6.68, d (8.0) 115.2 6.69, d (8.3)
125.3 6.96, dd 125.4 6.97, dd
(8.0, 2.0) (8.3, 2.1)
Figure 1. Experimental and calculated ECD spectra of 1.
146.4
152.6
17
27.1
2.71, dd
(13.0, 9.0)
27.2
2.72, dd
(13.3, 9.3)
27.2
27.2
2.56, dd
(13.0, 3.0)
2.57, dd
(13.3, 3.2)
18
19
20
21
22
23
24
121.3 5.03, m
135.9
121.5 5.07, m
136.0
122.8
135.5
26.2
18.4
22.9
27.2
29.1
122.8
135.3
26.2
18.5
22.8
27.2
29.1
26.4
18.3
23.2
27.3
30.3
1.73, s
1.69, s
1.15, s
0.99, s
2.09, m
2.02, m
26.6
18.5
23.3
27.5
30.4
1.74, s
1.70, s
1.16, s
1.00, s
2.09, m
2.02, m
25
26
27
28
29
125.6 4.87, m
133.6
125.7 4.87, m
133.8
123.9
133.1
25.9
18.1
36.3
124.0
133.0
25.9
18.1
36.3
25.9
18.2
37.3
1.65, s
1.49, s
1.98, m
26.1
18.4
37.5
1.66, s
1.50, s
1.98, m
1.92, dd
(13.5, 4.5)
1.92, dd
(14.0, 5.4)
30
31
32
33
34
35
36
37
38
45.2
149.5
2.62, m
45.4
149.6
2.63, m
43.7
43.7
148.2
112.9
17.8
148.2
112.8
17.8
113.0 4.45 (2H), s 113.1 4.46, d (3.9)
18.2
33.5
124.1 5.03, m
132.7
26.0
1.58, s
2.01, m
18.4
33.6
124.3 5.03, m
132.8
26.1
18.4
1.59, s
2.02, m
32.8
32.8
124.2
132.2
26.0
124.3
132.1
26.0
1.65, s
1.57, s
1.66, s
1.58, s
18.2
18.1
18.0
a
b
Recorded at 500 MHz (1H) and 125 MHz (13C). Recorded at 400
c
MHz (1H) and 100 MHz (13C). Recorded at 150 MHz (13C).
d
Recorded at 150 MHz (13C).
Figure 2. X-ray crystallographic structures of 1 and 2.
guttiferone F as the C-30 epimer of garcinol. To clarify this
problem, the 1H and 13C NMR spectra of 1 were remeasured in
CDCl3, and these data were similar to those of garcinol (Table 1
and Experimental Section).16−18 On the basis of the above
analysis, we concluded that guttiferone F is actually garcinol,
instead of 30-epi-garcinol (Table 2).
In order to further verify the epimeric configuration at C-30 of
guttiferone F, Fuller et al. transformed it via acid treatment into
the substituted tetrahydropyran (2a) (Scheme 2). When the
reaction was repeated using the same reaction conditions,1 the
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Note
Scheme 1. Structures of Garcinol, Cambogin, and Their C-30 Epimers
a
Reaction conditions: garcinol was refluxed with benzene solution containing traces of acid, such as HCl or CF3COOH, or heated at about 200 °C
for 5−10 min.
Scheme 2. Originally Reported and Reassigned Structures of Guttiferone F and 2a
Table 2. Comparison of the Chemical Shift Values of C-29−
C-32 for 1 in CDCl3 and Methanol-d4 + 0.1% TFA
confirmed that the structure of 2 and 2a was the same (Scheme
2). The absolute configuration of 2 was assigned as
(1R,5R,7R,30S) by single-crystal X-ray (Cu Kα) diffraction
data analysis, which showed that the absolute configuration of 2
was the same as that of cambogin (Figure 2). The Flack
parameter was refined, giving a value of 0.06(4), which indicates
the correct handedness. This is different from the orientation of
the substituent at C-30 originally assigned for 2a. In addition, the
NMR data of 2 in pyridine-d5 were also similar to the literature
data of cambogin (Table 3), the absolute configuration of which
was confirmed by X-ray crystallographic data analysis.19
Therefore, 2a is actually cambogin, not 30-epi-cambogin as
originally proposed.
recorded in methanol-d4 + 0.1%
recorded in CDCl3
garcinol (ref)
TFA
no.
1
guttiferone F (ref)
1
29
30
31
32
36.3
43.7
148.2
112.9
36.3
43.7
148.2
112.8
37.3
45.2
149.5
113.0
37.5
45.4
149.6
113.1
major reaction product 2 was obtained as colorless prisms from
1
an acetone/MeOH solution. Examination of the H and 13C
NMR data (Table 3), as well as the value of the specific rotation,
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Note
Table 3. 1H and 13C NMR Spectroscopic Data of 2a, 2, and Cambogin
recorded in methanol-d4 + 0.1% TFA
recorded in pyridine-d5
a
b
d
e
2a (ref)
2
cambogin (ref)
2
no.
1
2
3
4
5
6
7
8
δC
δH (J in Hz)
δC
δH (J in Hz)
δC
δH (J in Hz)
δC
δH (J in Hz)
69.6
196.3
110.2
173.9
52.6
46.7
47.5
40.0
69.6
196.5
c
69.2
195.0
127.2
171.4
52.2
46.8
47.0
39.8
69.1
195.0
127.1
171.4
52.1
46.7
173.8
52.8
47.2
47.6
40.2
1.50, m
2.28, d (14.0)
2.02, dd (14.5, 7.4)
1.50, m
2.28, d (14.6)
2.02, dd (14.6, 7.3)
1.59, dt (6.2, 6.1)
2.43, brd (14.1)
2.11, dd (14.1, 7.3)
46.9
39.8
1.59, m
2.42, brd (14.5)
2.09, dd (14.5, 7.4)
9
208.0
194.3
131.2
116.3
146.8
152.5
115.6
124.4
26.5
208.1
194.4
131.3
116.4
146.7
152.7
115.8
124.5
26.7
207.9
193.0
130.0
116.6
147.8
153.7
116.5
124.3
26.7
207.9
193.0
130.8
116.5
147.7
153.7
116.4
124.4
26.6
10
11
12
13
14
15
16
17
7.24, d (2.0)
7.24, d (2.0)
8.05, d (2.0)
8.08, d (2.0)
6.73, d (8.0)
6.73, d (8.0)
7.28, d (8.1)
7.28, d (8.2)
7.02, dd (8.0, 2.0)
2.63, dd (13.8, 8.0)
2.43, dd (13.5, 5.0)
4.91, m
7.03, dd (8.0, 2.0)
2.64, dd (12.9, 8.8)
2.44, dd (13.3, 5.3)
4.91, m
7.68, dd (8.1, 2.0)
2.95, dd (13.5, 7.6)
2.76, dd (13.7, 5.6)
5.42, brt (6.5)
7.69, dd (8.2, 2.0)
2.94, dd (13.5, 7.7)
2.75, dd (13.5, 5.5)
5.42, t (6.3)
18
19
20
21
22
23
24
121.1
135.3
26.3
18.2
22.8
27.0
30.5
121.3
135.6
26.3
18.2
23.0
27.2
30.7
121.7
134.5
26.6
18.8
27.1
23.1
30.4
121.6
134.4
26.5
18.7
27.0
23.0
30.3
1.58, s
1.57, s
1.14, s
0.98, s
2.67, m
2.12, m
4.91, m
1.59, s
1.58, s
1.15, s
0.98, s
2.68, m
2.12, m
4.91, m
1.57, s
1.71, s
1.05, s
1.30, s
1.56, s
1.70, s
1.04, s
1.29, s
3.20, m
1.81, m
5.07, m
3.21, ddd (14.4, 10.7, 9.5)
1.82, ddd (14.2, 9.5, 9.5)
5.09, brt (6.5)
25
26
27
28
29
126.2
133.5
26.1
18.5
29.0
126.7
134.1
26.1
18.8
29.4
126.4
132.9
26.5
19.0
29.1
126.4
133.3
26.4
18.9
29.0
1.68, s
1.66, s
3.02, dd (14.0, 3.0)
1.01, dd (14.0)
1.36, m
1.69, s
1.67, s
3.03, dd (14.2, 3.6)
1.03, m
1.38, m
1.74, s
1.91, s
3.27, dd (13.9, 3.1)
1.14, dd (13.9, 13.7)
1.66, dt (9.9, 5.0)
1.74, s
1.91, s
3.27, dd (14.2, 3.5)
1.14, m
1.66, m
30
31
32
33
34
44.7
88.1
29.0
21.3
30.5
44.8
88.4
29.2
21.7
30.7
43.8
87.2
21.7
29.4
30.4
43.7
87.1
21.6
29.3
30.3
0.90, s
1.25, s
2.05, m
1.83, m
5.20, m
0.90, s
1.26, s
2.08, m
1.83, m
5.21, t (7.0)
1.23, s
1.07, s
2.42 brd (14.1)
1.96 brd (14.1)
5.09, brt (6.5)
1.22, s
1.07, s
2.42, d (14.5)
1.98, m
5.07, m
35
36
37
38
122.8
134.6
26.1
123.1
134.8
26.1
122.8
133.7
26.2
122.7
133.7
26.1
1.78, s
1.63, s
1.79, s
1.64, s
1.68, s
1.56, s
1.67, s
1.55, s
17.8
18.2
18.3
18.2
a
b
c
d
Recorded at 500 MHz (1H) and 125 MHz (13C). Recorded at 400 MHz (1H) and 100 MHz (13C). Not detected. Recorded at 500 MHz (1H)
e
and 125 MHz (13C). Recorded at 400 MHz (1H) and 100 MHz (13C).
In summary, our reinvestigation of the structure determi-
nation of guttiferone F and 2a, using X-ray and NMR data
analyses and chemical transformation, revealed that the assigned
absolute configuration of C-30 in guttiferone F and 2a should be
inverted and their structures should be reassigned as garcinol
and cambogin, respectively. In recent years, the absolute
configurations of PPAPs have been determined by X-ray
diffraction data or comparison of their experimental and
calculated ECD spectra. However, the absolute configurations
of many PPAPs are difficult to define by single-crystal X-ray
diffraction because they are more often than not obtained as
gums or oils. Although ECD methods have been widely used to
determine the absolute configuration of many PPAPs, this
method is not suitable to assign the absolute configuration of a
stereocenter located far away from the chromophores,20 such as
C-30 in garcinol. The absolute configuration of many derivatives
of garcinol remains unknown and needs to be further
investigated.13,21,22 In view of such problems, our team is now
focusing on establishing a strategy to quickly synthesize a class of
PPAPs with chiral side chains by asymmetric total synthesis,
including 30-epi-garcinol.
1400
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Note
1670, 1598, 1517, 1440, 1371, 1292, 1182, 1105, 773, 640 cm−1;
HRESIMS m/z 603.3687 [M + H]+ (calcd for C38H51O6, 603.3686).
Crystal Data for 2. C38H50O6 (M = 602.78 g/mol): monoclinic,
space group P21 (no. 4), a = 14.5894(3) Å, b = 11.1597(3) Å, c =
20.4193(5) Å, β = 93.6280(10)°, V = 3317.87(14) Å3, Z = 4, T = 173.01
K, μ(Cu Kα) = 0.636 mm−1, Dcalc = 1.207 g/cm3, 22 097 reflections
measured (6.07° ≤ 2θ ≤ 136.87°), 11 551 unique (Rint = 0.0209, Rsigma
= 0.0294), which were used in all calculations. The final R1 was 0.0295
(I > 2σ(I)) and wR2 was 0.0826. Flack parameter = 0.06(4). Hooft =
0.06(4). Crystallographic data for 2 have been deposited at the
Cambridge Crystallographic Data Center (deposition number: CCDC
2032864).
Computational Details. The calculations of 1 were performed
using Gaussian 09. Conformational analysis was initially carried out
using Accelrys Discovery Studio 2.5 to generate conformers by Best,
then minimized by Smart Minimizer using the CHARMm molecular
mechanics force field. The minimized conformers were optimized at the
B3LYP/6-31G(d,g) level in the gas phase. Room-temperature
equilibrium populations were calculated according to the Boltzmann
distribution law. The ECD calculations were performed using TDDFT
at the B3LYP/6-31G(d,p) level in the gas phase. SpecDis 1.61 was used
to visualize the ECD spectra of 1 after a Boltzmann statistical weighting,
to generate the Gaussian curve, and for comparison with experimental
data.
EXPERIMENTAL SECTION
■
General Experimental Procedures. Optical rotations were
measured using an Autopol VI polarimeter. Ultraviolet absorption
spectra were recorded on a UV-2401 PC spectrophotometer. ECD
spectra were recorded on a Chirascan-plus spectrometer (Applied
Photophysics Ltd., Surrey, UK). IR spectra were recorded on a
PerkinElmer 577 spectrometer. NMR spectra were measured on Bruker
AV-400 and Bruker AV-600 spectrometers. Mass spectrometry was
performed on a SYNAPT G2-Si HDMS (Waters Corp., Manchester,
UK) with an electrospray ion source (Waters, Milford, MA, USA)
connected to a lock-mass apparatus, which performed real-time
calibration correction. Column chromatography was performed with
CHP20P MCI gel (75−150 μm, Mitsubishi Chemical Corporation,
Japan), silica gel (100−200 or 200−300 mesh, Qingdao Haiyang
Chemical Co., Ltd.), Sephadex LH-20 (GE Healthcare Bio-Sciences
AB, Sweden), and reversed-phase C18 silica gel (50 μm, YMC, Kyoto,
Japan). Precoated TLC sheets of silica gel 60 GF254 (Qingdao Haiyang
Chemical Co., Ltd.) were used.
Plant Material. The G. esculenta plants, including twigs and leaves,
were collected in Nujiang, Yunnan, People’s Republic of China, in
September 2014. The sample was identified by Dr. Hongmei Zhang,
Shanghai University of Traditional Chinese Medicine. A voucher
specimen (Herbarium No. 20140901) was deposited at the School of
Pharmacy, Shanghai University of Traditional Chinese Medicine.
Isolation of Compound 1. The dried and powdered plants of G.
esculenta, including twigs and leaves (23 kg), were extracted by refluxing
with 95% EtOH (4 × 200 L). The combined crude extracts were
evaporated, diluted with H2O, and extracted with petroleum ether and
EtOAc. The petroleum ether-soluble extract (350 g) was subjected to
passage over an MCI column eluted with H2O and 95% EtOH. The
95% EtOH-eluting fraction (249.3 g) was chromatographed by a silica
gel column using a gradient of petroleum ether/acetone (100:0 to
50:50, v/v) to afford 16 fractions, A−P, as described previously.23
Fraction D was separated by ODS and eluted in a step-gradient manner
with MeOH/H2O (5:95 to 100:0), to afford compound 1 (1.5 g).
Garcinol (1): yellow gum; [α]2D0 −160 (c 0.04, CHCl3); UV (MeOH)
λmax (log ε) 280 (3.47) nm; ECD (c 4.85 × 10−4 M, MeOH) λmax nm
(Δε) 198 (−27.99), 225 (+13.12), 269 (−21.29); IR (KBr) νmax 3396,
2969, 2923, 1727, 1639, 1602, 1523, 1442, 1375, 1290, 1193, 1116, 892,
777 cm−1; 1H NMR (600 MHz, CDCl3) δ 7.01−6.98 (m, 2H), 6.65 (d,
J = 8.2 Hz, 1H), 5.10 (m, 1H), 5.04 (d, J = 8.2 Hz, 1H), 4.92 (t, J = 7.0
Hz, 1H), 4.40 (d, J = 24.0 Hz, 2H), 2.77−2.71 (m, 2H), 2.59−2.56 (m,
1H), 2.35 (d, J = 14.0, 1H), 2.15−2.08 (m, 4H), 1.95−2.01 (m, 2H),
1.93−1.85 (m, 2H), 1.80 (s, 3H), 1.73 (s, 3H), 1.69 (s, 3H), 1.67 (s,
3H), 1.60 (s, 3H), 1.54 (s, 3H), 1.44−1.42 (m, 2H), 1.25 (s, 3H), 1.15
(s, 3H), 1.05 (m, 1H), 1.01 (s, 3H); HRESIMS m/z 603.3687 [M +
H]+ (calcd for C38H51O6, 603.3686).
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c01031.
HRESIMS, IR, ECD, NMR spectra, and X-ray crystallo-
graphic data of compounds 1 and 2 (PDF)
Single-crystal X-ray diffraction data for compound 1
(CIF)
Single-crystal X-ray diffraction data for compound 2
(CIF)
AUTHOR INFORMATION
■
Corresponding Authors
Hong-Xi Xu − Shuguang Hospital, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China; orcid.org/0000-0001-6238-4511;
Phone: +86-21-51323089; Email: xuhongxi88@gmail.com
Hong Zhang − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China; Phone: +86-21-51322066;
Email: zhnjau19851010@163.com
Crystal Data for 1. C40H53NO6 (M = 643.83 g/mol): monoclinic,
space group P21 (no. 4), a = 10.8272(4) Å, b = 9.0795(3) Å, c =
19.3623(7) Å, β = 103.0290(10)°, V = 1854.42(11) Å3, Z = 2, T = 173.0
K, μ(Cu Kα) = 0.607 mm−1, Dcalc = 1.153 g/cm3, 13 031 reflections
measured (4.684° ≤ 2θ ≤ 136.366°), 6546 unique (Rint = 0.0253, Rsigma
= 0.0339), which were used in all calculations. The final R1 was 0.0350
(I > 2σ(I)) and wR2 was 0.0943. Flack parameter = 0.14(7). Hooft =
0.14(7). Crystallographic data for 1 have been deposited at the
Cambridge Crystallographic Data Center (deposition number: CCDC
2032861).
Authors
Dan Zheng − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Jia-Ming Jiang − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Si-Min Chen − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Shi-Jie Wan − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Conversion of 1 to 2. A solution of 10 mg of 1 in 5 mL of toluene
and 30 μL of concentrated HCl was refluxed for 40 min. After cooling,
the reaction mixture was washed with H2O (3 × 5 mL) and evaporated
to dryness. Compound 2 (3.5 mg) was obtained as colorless prismatic
crystals from acetone/MeOH. The conversion can also be achieved
thermally by heating 1 (10 mg) at 200 °C for 5 min, from which 5 mg of
2 was obtained under the same recrystallization conditions.
Cambogin (2): colorless prismatic crystal; mp 238−239 °C; [α]D20
−132 (c 0.02, CHCl3); UV (MeOH) λmax (log ε) 234 (3.66), 279
(3.73) nm; ECD (c 6.31 × 10−4 M, MeOH) λmax nm (Δε) 228 (+8.18),
263 (−10.03), 343 (+3.35); IR (KBr) νmax 3461, 2971, 2925, 1720,
Han-Gui Ren − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
1401
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J. Nat. Prod. 2021, 84, 1397−1402

Journal of Natural Products
pubs.acs.org/jnp
Note
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Bian, Z.; Yang, D.; Chen, S. U.S. Patent 9,408,811B2, 2016.
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1980, 21, 1975−1978.
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(18) Sang, S.; Liao, C.-H.; Pan, M.-H.; Rosen, R. T.; Lin-Shiau, S.-Y.;
Lin, J.-K.; Ho, C.-T. Tetrahedron 2002, 58, 10095−10102.
(19) Marti, G.; Eparvier, V.; Moretti, C.; Susplugas, S.; Prado, S.;
Grellier, P.; Retailleau, P.; Gueritte, F.; Litaudon, M. Phytochemistry
2009, 70, 75−85.
(20) Yang, X. W.; Grossman, R. B.; Xu, G. Chem. Rev. 2018, 118,
3508−3558.
(21) Liu, X.; Yu, T.; Gao, X. M.; Zhou, Y.; Qiao, C. F.; Peng, Y.; Chen,
S. L.; Luo, K. Q.; Xu, H. X. J. Nat. Prod. 2010, 73, 1355−1359.
(22) Xia, Z. X.; Zhang, D. D.; Liang, S.; Lao, Y. Z.; Zhang, H.; Tan, H.
S.; Chen, S. L.; Wang, X. H.; Xu, H. X. J. Nat. Prod. 2012, 75, 1459−
1464.
Gan Chen − School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Gang Xu − State Key Laboratory of Phytochemistry and Plant
Resources in West China and Yunnan Key Laboratory of
Natural Medicinal Chemistry, Kunming Institute of Botany,
Chinese Academy of Sciences, Kunming 650201, People’s
Republic of China; orcid.org/0000-0001-7561-104X
Hua Zhou − Shuguang Hospital, Shanghai University of
Traditional Chinese Medicine, Shanghai 201203, People’s
Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jnatprod.0c01031
Author Contributions
#D.Z. and J.-M.J. contributed equally to this work.
Notes
(23) Zheng, D.; Zhang, H.; Jiang, J.-M.; Chen, Y.-Y.; Wan, S.-J.; Lin,
Z.-X.; Xu, H.-X. Nat. Prod. Res. 2019, 1−8.
The authors declare no competing financial interest.
Crystallographic data for the structure(s) have been deposited
with the Cambridge Crystallographic Data Centre. Copies of the
data can be obtained, free of charge, on application to the
Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: + 44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
NOTE ADDED AFTER ASAP PUBLICATION
■
This paper was published ASAP on March 8, 2021, with an error
in the TOC and Abstract graphic. The corrected version was
reposted on March 24, 2021.
ACKNOWLEDGMENTS
■
This research was supported by the Xinglin Talent Tracking
Program (H.Z.), the NSFC-Joint Foundation of Yunnan
Province (No. U1902213), and the Guangdong Province Key
Area R & D Program of China (No. 2020B1111110003).
Calculations with the Gaussian 09 program were performed on
computers of the National Supercomputing Center in Shenzhen
(Shenzhen Cloud Computing Center). The authors are grateful
to Dr. S. Liang for fruitful discussions regarding structural
elucidation and manuscript preparation.
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