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Absolute Configuration of 12S‑Deoxynortryptoquivaline from
Ascidian-Derived Fungus Aspergillus clavatus Determined by
Anisotropic NMR and Chiroptical Spectroscopy
Elisa Doro-Goldsmith,
#
Qi Song,
#
Xiao-Lu Li, Xiao-Ming Li, Xue-Yi Hu, Hong-Lei Li, Hao-Ran Liu,
Bin-Gui Wang,*and Han Sun*
Cite This: J. Nat. Prod. 2024, 87, 381−387
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sı Supporting Information
ABSTRACT: Tryptoquivalines are highly toxic metabolites
initially isolated from the fungus Aspergillus clavatus. The relative
and absolute configuration of tryptoquivaline derivates was
primarily established by comparison of the chemical shifts, NOE
data, and ECD calculations. A de novo determination of the
complete relative configuration using NMR spectroscopy was
challenging due to multiple spatially separated stereocenters,
including one nonprotonated carbon. In this study, we isolated a
new tryptoquivaline derivative, 12S-deoxynortryptoquivaline (1),
from the marine ascidian-derived fungus Aspergillus clavatus AS-
107. The correct assignment of the relative configuration of 1was
accomplished using anisotropic NMR spectroscopy, while the
absolute configuration was determined by comparing calculated
and experimental ECD spectra. This case study highlights the effectiveness of anisotropic NMR parameters over isotropic NMR
parameters in determining the relative configuration of complex natural products without the need for crystallization.
The tryptoquivalines constitute a series of highly toxic
metabolites that induce tremors and were initially
discovered in Aspergillus clavatus in 1975.
1
This fungus was
one of several collected from mold-infested rice found in a
Thai household where a child had died from an unidentified
toxicosis. The complete relative and absolute configurations of
the tryptoquivalines remained unknown until 1979, when
nortryptoquivaline was revealed by Springer using single-
crystal X-ray diffraction.
2
Tryptoquivaline derivatives have also
been isolated from other fungi, such as the mangrove-derived
fungus Cladosporium sp. PJX-41.
3
These tryptoquivalines have
shown significant activity against influenza virus A (H1N1).
Furthermore, subsequent in silico studies have suggested
deoxytryptoquivaline and deoxynortryptoquivaline as potential
inhibitors to the SARS-CoV-2 main protease (Mpro),
4,5
which
is currently considered as a key target for preventing infectious
diseases caused by the SARS-CoV-2 virus.
6
Over the past two decades, anisotropic NMR spectroscopy
has revolutionized the field of structural elucidation of complex
natural products, eliminating the need for crystallization.
7−9
Anisotropic NMR parameters, such as residual dipolar
coupling (RDC), residual chemical shift anisotropy (RCSA),
and residual quadrupolar coupling (RQC), have been used
extensively to determine the constitution, relative configu-
ration, and conformation of challenging organic mole-
cules.
10−15
These long-range NMR parameters prove partic-
ularly valuable in studies involving molecules with multiple
spatially separated stereocenters, proton-deficient molecules,
and conformationally flexible molecules.
In this study, we characterized a new tryptoquivaline
alkaloid, 12S-deoxynortryptoquivaline (1), from the marine
ascidian-derived fungus Aspergillus clavatus AS-107. Here, we
employed anisotropic NMR spectroscopy to determine the
relative configuration of compound 1(Figure 1). 12S-
Deoxynortryptoquivaline presents a substantial challenge for
conventional stereochemical elucidation using NMR spectros-
copy. This is because the molecule features five stereocenters,
some of which are spatially separated and one of which is a
quaternary carbon. To address this challenge, we adopted a
cross-validation approach, leveraging the recent development
of the program StereoFitter.StereoFitter is a module in Mnova
from Mestrelab Research that can incorporate various types of
isotropic and anisotropic NMR parameters for stereochemical
and conformational analysis. Notably, in this study, the analysis
Received: November 27, 2023
Revised: January 9, 2024
Accepted: January 9, 2024
Published: January 30, 2024
Articlepubs.acs.org/jnp
© 2024 The Authors. Published by
American Chemical Society and
American Society of Pharmacognosy 381
https://doi.org/10.1021/acs.jnatprod.3c01157
J. Nat. Prod. 2024, 87, 381−387
This article is licensed under CC-BY 4.0

of RDCs alone effectively distinguished the correct relative
configuration among the 16 possible ones. Although isotropic
NMR data, including 13C chemical shifts and NOEs, supported
the results obtained from the RDC analysis, they did not offer
the same level of discrimination as the anisotropic NMR
analysis. Finally, we conclusively determined the absolute
configuration of 12S-deoxynortryptoquivaline (1) by compar-
ing the computed and experimental ECD spectra.
■RESULTS AND DISCUSSION
Identification of 12S-Deoxynortryptoquivaline (1).
Compound 1was initially isolated as a white amorphous
powder. Its molecular formula was determined to be
C28H28O6N4by analysis of HRESIMS data at m/z517.2079
[M + H]+(calculated for C28H29O6N4, 517.2082, Figure S1),
requiring 17 degrees of unsaturation. The 1H and 13C chemical
shift assignments of the compound were performed using 1D
1H and 13C, and 2D COSY, HSQC, and HMBC spectra (Table
1,Figures S2−S7). From the HSQC spectrum, eight individual
chemical shifts were identified within an overlapped aromatic
portion of the 1H spectrum (δH= 7.37−8.24 ppm). The COSY
and HMBC spectra were used to distinguish the two aromatic
ring systems at C4−C9 and C19−C24 and to assign the 1H
and 13C signals. Quaternary carbons were identified by
comparing 13C and HSQC spectra, and their assignments
were achieved using the HMBC spectrum, with key
correlations shown in Figure 1. All 1H and 13C chemical shifts
of compound 1could be confidently assigned, aside from
prochiral C13−H13a/b methylene and prochiral methyl
groups C29−H29 and C30−H30, which could not be
distinguished with certainty. The 1H and 13C NMR data of
compound 1are similar to those of deoxynortryptoquivaline
3
isolated from the mangrove-derived fungus Cladosporium sp.
PJX-41. Further structural identification confirmed that they
should have the same planar structure, but different relative
and absolute configurations.
Measurement of NMR Structural Data. The 3JHH
couplings of compound 1were measured from the isotropic
1H spectrum (Table 1). NOE correlations were measured from
the 1H−1H-NOESY spectrum, and peak intensities were
extracted from the correlations to calculate 1H−1H distances
according to the isolated spin-pair approximation (Table S1).
As part of this calculation, a reference distance of 1.78 Å was
used between geminal protons H13a and H13b.
To measure the RDCs of 1, we used an oligopeptide-based
alignment medium, AAKLVFF (28.8 mg/mL), in MeOH-d4
(Table S2).
17
In methanol, AAKLVFF undergoes a self-
assembly process to form nanotubes over several days. During
this time, the degree of alignment of the analyte increases, and
the necessary spectra can be acquired using standard NMR
equipment and experiments. For RDC extraction, we acquired
two 1H−13C-CLIP-HSQC spectra
16
under the isotropic and
fully aligned, anisotropic states (Figure S8). This anisotropic
state was achieved 4 days after AAKLVFF was added to the
sample, resulting in a deuterium splitting of 13.5 Hz (Figure
S9). The RDCs were calculated as the difference between
couplings in the fully aligned state and the isotropic state. In
total, 18 1DCH RDCs were measured for compound 1, with
only one coupling (C13−H13) not being measured due to an
irregular peak shape in the anisotropic spectrum (Table S2).
Additionally, we acquired ΔΔRCSAs of compound 1from
the same sample following the previously proposed proce-
dure.
17
These ΔΔRCSA values were extracted from two
anisotropic 13C spectra measured on days 1 and 4 using three
references: (i) C-28, which exhibited the smallest theoretically
calculated chemical shift anisotropy (CSA); (ii) C-12, which
exhibited the second-smallest theoretically calculated CSA; and
(iii) the MeOH-d4solvent. In total, we measured 26
ΔΔRCSAs for compound 1(Table S3).
Determination of the Relative Configuration. Com-
pound 1possesses five unknown stereocenters at C2, C3, C12,
C15, and C27 (Figure 1), resulting in 16 possible relative
configurations, RC1−RC16 (Table S4). To determine the
correct relative configuration, we employed a cross-validation
approach. For this, we first generated a conformational
ensemble for each possible relative configuration through a
combination of a molecular mechanics (MM)-based conforma-
Figure 1. Chemical structure and key HMBC correlations (indicated
as arrows) of compound 1.
Table 1. NMR Spectroscopic Data (750 MHz, CH3OH-d4)
for 12S-Deoxynortryptoquivaline (1)
position δC, type δH(Jin Hz)
2 87.1, CH 5.48, s
3 87.8, C
4 133.3, C
5 126.8, CH 7.78, d (8.2)
6 127.5, CH 7.37, t (7.6)
7 132.8, CH 7.55, m
8 118.4, CH 7.52, m
9 142.2, C
11 172.5, C
12 56.9, CH 5.93, t (9.8)
13 32.6, CH22.77, dd (13.1, 9.4)
3.54, dd (13.1, 10.2)
14 179.2, C
15 61.6, CH 3.83, q (7.0)
18 163.1, C
19 121.8, C
20 127.5, CH 8.23, d (8.0)
21 129.2, CH 7.60, t (7.7)
22 136.5, CH 7.89, t (7.7)
23 128.5, CH 7.76, d (8.5)
24 147.7, C
26 154.8, C
27 81.0, CH 5.64, d (9.7)
28 33.5, CH 2.49, m
29 or 30 19.1, CH30.97, d (6.5)
29 or 30 19.4, CH31.17, d (6.7)
32 171.8, C
33 20.7, CH32.22, s
34 17.9, CH31.50, d (7.0)
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382

tional search and density functional theory (DFT)-based
structural optimizations. As a result, we obtained a structural
ensemble ranging from 3 to 19 conformers for each relative
configuration (Table S4). The detailed procedure is described
in the Computational Methods.
We then performed a fitting of the 16 obtained structural
ensembles against 15 1DCH values. This fitting included all
couplings except for prochiral C13−H13a/b, which were
omitted due to their relatively large experimental errors, and
the prochiral methyls C29−H29 and C30−H30, as these could
not be confidently distinguished. In this analysis, a single
alignment tensor approximation was considered, where all
conformers adopt the same alignment tensor.
18
The calcu-
lations were carried out using the program package StereoFitter,
a recent MNova plug-in for the structural elucidation of
organic molecules based on isotropic and anisotropic NMR
data. Through StereoFitter, the alignment tensor and the
conformational population were determined based on a model
selection procedure that employed a combination of the
Levenberg−Marquardt least-squares optimization and the
Akaike Information Criterion (AIC).
19,20
The determined
conformer population and tensor parameters were subse-
quently used to back-calculate the theoretical RDCs, and the
agreement between these predicted and experimental values
was assessed through the AIC value. A decrease in the AIC
indicates an improved accuracy of the selected model,
suggesting that the configuration with the smallest AIC is
the most likely relative configuration. The results summarized
in Figure 2 clearly demonstrate that the RC6 configuration
(C2:R*, C3:S*, C12:S*, C15:S*, C27:S*) exhibits the best
agreement between the back-calculated and experimental RDC
data. The second-ranking configuration showed a nearly
doubled AIC value as compared to the best-ranking one,
Figure 2. (a) Comparison of the AIC value derived from the RDC analysis for the 16 possible relative configurations, and the correlation between
back-calculated and experimental RDCs using (b) all 15 1DCH values and (c) excluding the RDC value of C33−H33, which is located on a flexible
side-chain.
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383

indicating a very high discrimination probability of the RDC
data.
Furthermore, we plotted the back-calculated RDCs against
the experimental ones and calculated the Qfactor
21
for the
top-ranked configuration, RC6. It is noteworthy that
incorporating all 15 RDCs during the fitting process resulted
in only a moderate level of correlation, yielding a Qfactor of
0.44 (Figure 2b). Two primary factors could potentially
account for the intermediate correlation observed between the
experimental and back-calculated RDC data: (i) Employing
AAKLVFF as the alignment medium, we obtained very large
RDC values for compound 1, ranging from −91 to 74 Hz.
Generally, an optimal alignment should yield RDCs within the
range of 10−30 Hz. Values substantially exceeding this range
introduce second-order effects in the NMR spectrum, causing
signal distortion and subsequently leading to larger errors in
RDC measurements. Achieving an optimal RDC range often
involves multiple optimization steps;
22
however, given the
limited availability of novel natural products such as compound
1, conducting an extensive optimization procedure was not
feasible. (ii) The initial ensembles generated through an MM-
based conformational search and subsequent DFT optimiza-
tions, followed by conformer filtering based on the DFT-
derived energy, did not adequately account for conformational
flexibility. For instance, when excluding the RDC value
corresponding to C33−H33, situated in a flexible side-chain,
a reduced Qfactor of 0.39 was obtained (Figure 2b).
Nevertheless, despite the correlation and Qfactor for the
correct relative configuration RC6 being suboptimal, the
differentiation of the best-fitting configuration from the others
was sufficient to safely assign the relative configuration in this
scenario.
In addition, we employed isotropic structural NMR data,
including NOEs (Figure 3a) and 13C chemical shifts (Figure
3b), to cross-validate the 16 possible relative configurations.
Here, only NOE correlations between nuclei separated by
more than five bonds and with a distance <5 Å were included
in the analysis. We also selected two 3JHH couplings, excluding
all vicinal 3JHH couplings to methyl or aromatic groups as they
did not provide any stereochemical information (Table S5).
These two couplings were used in combination with NOEs
and 13C shifts for stereochemical assessment (Figure 3c). In
this study, we exclusively used the 13C chemical shifts in the
stereochemical assignment as the correlation between
computed and experimental 1H chemical shifts was only
intermediate. The results, as summarized in Figure 3, indicate
that both NOEs and 13C chemical shifts support RC6 as the
correct configuration, although NOEs provide less discrim-
ination between the first- and second-ranking configurations.
While the combination of the three types of isotropic NMR
data supports RC6 as the correct configuration, the
discrimination power of the isotropic NMR data is not as
robust as the RDC analysis (Table S6). Notably, although the
RDCs, NOEs, and 13C chemical shifts all point toward RC6 as
the best-scoring configuration, the second-best ranking
configuration suggested by all three analyses is significantly
different.
We also attempted to use the acquired ΔΔRCSA data to
assess the 16 possible relative configurations. Our previous
studies have demonstrated the power of ΔΔRCSAs in
stereochemical assignment, particularly for proton-deficient
molecules.
17,23
To our surprise, despite compound 1also
containing a quaternary carbon stereocenter (C3), ΔΔRCSAs
provided very poor discrimination among the 16 relative
configurations (Figure S12).
Determination of the Absolute Configuration. Finally,
we determined the absolute configuration of compound 1
through a comparison between the experimental and back-
calculated ECD spectra in MeOH-d4(Figure 4). Experimental
and computational details are provided in the Computational
Methods. The experimental ECD spectrum displayed a key
positive Cotton effect at 208 nm and a key negative Cotton
effect at 230 nm, respectively. These spectral bands are well
reproduced in the computed ECD spectra, thus resulting in an
unambiguous determination of the absolute configuration of 1
as C2:R, C3:S, C12:S, C15:S, and C27:S(Figure 5). As
compared to the originally identified deoxynortryptoquivaline,
3
compound 1possesses a different absolute configuration at
C12. Thus, compound 1was named 12S-deoxynortryptoquiva-
line as a new quinazolinone alkaloid.
Figure 3. Comparison of the AIC values for the lowest (green), second-lowest (yellow), and highest (red) scoring relative configurations when
using (a) NOEs, (b) 13C chemical shifts, and (c) a combination of the two along with 3JHH couplings.
Figure 4. Comparison of the experimental (black) and computed
RSSSS (red) and SRRRR (blue) ECD spectra of compound 1in
MeOH-d4for determination of the absolute configuration.
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384

■CONCLUSIONS
12S-Deoxynortryptoquivaline (1) falls within the category of
challenging natural products for which determining the relative
configuration using conventional NMR parameters proves to
be difficult. We made attempts to leverage various types of
isotropic and anisotropic NMR data to establish the relative
configuration. Remarkably, the RDC analysis yielded the most
discerning results among the 16 possible relative config-
urations. Although isotropic NMR data, including chemical
shifts and NOEs, corroborated the results from the anisotropic
NMR data, they did not yield the same level of distinctiveness
as the RDC analysis. Finally, we conclusively determined the
absolute configuration of 12S-deoxynortryptoquivaline (1) by
comparison of the experimental and computed ECD spectra as
C2:R, C3:S, C12:S, C15:S, and C27:S, with an ensemble
comprising two primary conformers in the MeOH (Figure 5).
■EXPERIMENTAL SECTION
General Experimental Procedures. NMR spectra were acquired
on a Bruker AV750 MHz spectrometer using a 5 mm TCI Cryoprobe.
Chemical shifts (δ) were referenced to the MeOH-d4solvent to
provide specific shifts. Oligopeptide AAKLVFF (purity >98%) was
purchased from CSBio (Shanghai) Ltd. The 3 mm NMR tubes and
MeOH-d4(purity 99.8%) were purchased from Deutero GmbH. Mass
spectra were recorded on an API QSTAR Pulsar 1 mass spectrometer
(Applied Biosystems, Foster City, CA). UV spectra were read from a
PuXi TU-1810 UV−visible spectrophotometer (Shanghai Lengguang
Technology Co., Ltd., Shanghai, China). Column chromatography
(CC) was used with silica gel (200−300 mesh, Qingdao Haiyang
Chemical Factory, Qingdao, China), Lobar LiChroprep RP-18 (40−
60 μm, Merck, Darmstadt, Germany), and Sephadex LH-20 (18−110
μm, Merck, Germany). Thin layer chromatography (TLC) was
performed with silica gel GF254 precoated plates (100 ×200 mm,
Qingdao Haiyang Chemical Group Corp., Qingdao, China). A
separation and purification experiment was carried out with distilled
organic solvents.
Biological Material. The fungal strain Aspergillus clavatus AS-107
was isolated from the fresh tissue of a marine species of ascidian,
which was collected from Lombok Island, Indonesia in October 2016.
The fungus was identified as A. clavatus based on its ITS region
sequence, which was found to be identical (100%) to that of A.
clavatus TA30 (HQ392482). The sequence information on the fungus
was deposited in GenBank with the accession no. MK785134. The
strain is preserved at the Key Laboratory of Experimental Marine
Biology, Institute of Oceanology, Chinese Academy of Sciences
(IOCAS).
Fermentation, Extraction, and Isolation. Fresh mycelia of A.
clavatus AS-107 were grown on a PDA medium with seawater at 28
°C for 5 days and then inoculated into 98 ×1 L Erlenmeyer flasks
with rice solid medium (70 g of rice, 0.3 g of peptone, 0.1 g of corn
flour, and 100 mL of naturally sourced and filtered seawater), and
statically cultured for 30 days at room temperature. The fermentation
products were extracted three times with EtOAc, resulting in a crude
extract of 115.7 g obtained through vacuum distillation. The crude
extract was then fractionated by Si gel vacuum liquid chromatography
(VLC), eluting with different solvents of increasing polarity from
petroleum ether (PE) to MeOH to yield nine fractions (fractions 1−
9). Fraction 5 (PE−EtOAc 1:1, 12.3 g) was further segmented by
column chromatography (CC) over Lobar LiChroprep RP-18 with a
MeOH−H2O gradient (from 10:90 to 100:0) to yield fractions 5.1−
5.12. Fraction 5.8 (57.0 mg) was further purified by CC on Si gel
eluting with a CH2Cl2−MeOH gradient (from 200:1 to 20:1) and
then by Sephadex LH-20 eluting with MeOH to obtain compound 1
(5.2 mg).
12S-Deoxynortryptoquivaline (1). White amorphous powder;
[α]25D−168 (c0.38, MeOH); UV (MeOH) λmax (log ε) 228
(4.54), 265 (4.03), 317 (3.53) nm; ECD (0.54 mM, MeOH-d4)λmax
(Δε) 208 (+18.04), 230 (−15.78) nm; 1H and 13C NMR data, Table
1; HRESIMS m/z517.2079 [M + H]+(calcd for C28H29O6N4,
517.2082).
Measurement of the Isotropic NMR Spectra. Compound 1
(1.5 mg) was dissolved in 250 μL of MeOH-d4in a 3 mm NMR tube.
1D 1H, 13C and 2D HSQC, HMBC, COSY, NOESY, and CLIP-
HSQC experiments were acquired at 300 K at a 750 MHz Bruker
NMR spectrometer (750 and 187.5 MHz for 1H and 13C,
respectively) that was equipped with a 5 mm TCL cryoprobe (z-
gradient). All experiments used original Bruker pulse sequences, aside
from the CLIP-HSQC, which used a home-modified pulse program.
The number of scans for the above experiments was 24, 4000, 22, 30,
16, 24, and 26, respectively. The mixing time of the NOESY was 74
μs.
Measurement of RDC and ΔΔRCSA Data of Compound 1.
After the acquisition of the above parameters, the AAKLVFF
oligopeptide (7.2 mg) was then added to the solution, and the tube
was inverted 1 time to achieve proper mixing and obtain the initial
alignment condition. The sample was then stored at 3.8 °C and
inverted 8 times per day. After 4 days, the aligned phase reached the
equilibrated state (ΔνQ(2H) = 13.5 Hz). The acquisition of 1D 13C
and 2D CLIP-HSQC experiments was carried out under both initial
and equilibrated alignment conditions. A total of 18 RDCs and 26
ΔΔRCSAs were obtained. To ensure the accuracy of their
measurement, the RDC data were extracted five times from the
same spectra, and the averaged value and standard deviation were
derived from these five measurements.
Measurement of ECD Spectrum. A CD spectrum was measured
on a JASCO J-720 instrument. Compound 1was dissolved in MeOH-
d4to a concentration of 5.38 ×10−4mol/L. The applied acquisition
parameters are as follows: cuvette of 0.1 cm path-length, 200 μL
sample solutions, baseline correction, room temperature, data pitch
(0.1 nm), scanning mode (continuous), wavelength range (180−400
nm), and accumulation (5).
Computational Methods. A conformer ensemble was generated
for each of the 16 possible relative configurations using the GMMX
add-on module in GaussView 6. DFT optimization and energy
calculation of the conformers were performed at the B3LYP/6-31G+*
level with solvation modeled using IEFPCM and MeOH parameters
in the program Gaussian 16.
24
All conformers with Boltzmann
population ≤5% in the energy calculations were discarded, and NMR
calculations were performed on the remainder at the GIAO/B3LYP/
6-311+G*level using IEFPCM MeOH solvation. The selected
conformers of each relative configuration were aligned in PyMOL.
25
Fitting of the NOEs, 13C chemical shifts, 3JHH couplings, and 1DCH
data to each conformational ensemble of the 16 possible
configurations was performed in StereoFitter, a Plug-in for MNova.
Due to some technical issues in the current version of StereoFitter,
MSpin was used for the ΔΔRCSA analysis and calculation of the Q
factor. ECD spectra were simulated for the RDC-selected conformers
(rc6_4 and rc6_6) under time-dependent density functional theory at
the B3LYP/6-311+G*level using MeOH solvent. The calculations
were carried out in Gaussian16.
Figure 5. (a) The correct absolute configuration of compound 1and
(b) the determined structural ensemble of 1from RDC analysis.
Journal of Natural Products pubs.acs.org/jnp Article
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385

■ASSOCIATED CONTENT
*
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c01157.
General information on experimental procedures,
characterization data, and NMR spectra for compound
1(PDF)
Additional NMR details (ZIP)
■AUTHOR INFORMATION
Corresponding Authors
Bin-Gui Wang −CAS and Shandong Province Key
Laboratory of Experimental Marine Biology, Institute of
Oceanology, Chinese Academy of Sciences, Qingdao 266071,
China; University of Chinese Academy of Sciences, Beijing
100049, China; Email: [email protected]
Han Sun −Leibniz-Forschungsinstitut fur Molekulare
Pharmakologie (FMP), Berlin 13125, Germany; Institute of
Chemistry, Technische Universität Berlin, Berlin 10623,
Germany; orcid.org/0000-0002-1655-0838;
Email: [email protected]
Authors
Elisa Doro-Goldsmith −Leibniz-Forschungsinstitut fur
Molekulare Pharmakologie (FMP), Berlin 13125, Germany;
School of Chemistry, The University of Edinburgh, Edinburgh
EH9 3FJ, United Kingdom; orcid.org/0000-0002-6491-
646X
Qi Song −CAS and Shandong Province Key Laboratory of
Experimental Marine Biology, Institute of Oceanology,
Chinese Academy of Sciences, Qingdao 266071, China
Xiao-Lu Li −Leibniz-Forschungsinstitut fur Molekulare
Pharmakologie (FMP), Berlin 13125, Germany
Xiao-Ming Li −CAS and Shandong Province Key Laboratory
of Experimental Marine Biology, Institute of Oceanology,
Chinese Academy of Sciences, Qingdao 266071, China
Xue-Yi Hu −CAS and Shandong Province Key Laboratory of
Experimental Marine Biology, Institute of Oceanology,
Chinese Academy of Sciences, Qingdao 266071, China
Hong-Lei Li −CAS and Shandong Province Key Laboratory
of Experimental Marine Biology, Institute of Oceanology,
Chinese Academy of Sciences, Qingdao 266071, China
Hao-Ran Liu −Leibniz-Forschungsinstitut fur Molekulare
Pharmakologie (FMP), Berlin 13125, Germany; Institute of
Chemistry, Technische Universität Berlin, Berlin 10623,
Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jnatprod.3c01157
Author Contributions
#
E.D.-G. and Q.S. contributed equally.
Notes
The authors declare no competing financial interest.
■ACKNOWLEDGMENTS
This research was financially supported by the Leibniz-
Forschungsinstitut fur Molekulare Pharmakologie (FMP) and
the Deutsche Forschungsgemeinschaft (DFG, German Re-
search Foundation) under the DFG/CAPES Collaborative
Research Initiative (418729698). X.-L.L. acknowledges the
financial support from the Chinese Scholarship Council. We
thank Prof. A. Navarro-Vázquez for valuable discussions, P.
Schmieder for assistance with the NMR measurements, and H.
Nikolenko for help with the ECD measurement.
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