The Biomimetic Total Syntheses of the Antiplasmodial Tomentosones A and B

Article abstract of DOI:10.1021/acs.orglett.0c02943

The first biomimetic total syntheses of natural phloroglucinols tomentosones A and B and their analogues have been accomplished. The synthetic strategy primarily referred to the potential biosynthetic precursors and their possible sequence of segments ass

Full text of DOI:10.1021/acs.orglett.0c02943

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Letter
The Biomimetic Total Syntheses of the Antiplasmodial
Tomentosones A and B
Xiao Zhang,⊥ Chunmao Dong,⊥ Guiyun Wu, Luqiong Huo, Yunfei Yuan, Yingjie Hu,* Hongxin Liu,*
and Haibo Tan*
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ABSTRACT: The first biomimetic total syntheses of natural phloroglucinols
tomentosones A and B and their analogues have been accomplished. The
synthetic strategy primarily referred to the potential biosynthetic precursors
and their possible sequence of segments assembly by chemological evolution
of the structural entities and enabled rapid access of the titled compounds in a
practical fashion.
olycyclic polymethylated phloroglucinols (PPPs) bearing
Pa fascinating tetramethylcyclohexenedione or acylphlor-
oglucinol scaffold represent the most characteristic family of
secondary metabolites that are mainly encountered from the
Myrtaceae and Guttiferae plants.1 Because of their architectural
complexity as well as diverse structure features, the chemistry
of PPPs have recently become one of hotspots in natural
product research and generated considerable attention among
natural product chemists.1,2 Moreover, the emerging significant
biological activities, such as potent antibacterial,3 immunosup-
pressive effect,4 anti-inflammatory,5 and antiplasmodial6
activities have sparked remarkable efforts toward the develop-
ment of pharmaceuticals and agrochemicals by employing
PPPs as attractive lead compounds or popular synthetic targets
Figure 1. Structures of representative acylphloroglucinols.
in recent years.1,7,8
Rhodomyrtone (1), rhodomyrtosone A (2), rhodomyrto-
sone G (3), and rhodomyrtosone C (4) are examples
representing this class of compounds, whose structural motifs
are situated on a tetramethylcyclohexenedione or acylphlor-
oglucinol scaffold. Tomentosones A (5) and B (6) were
isolated from the Rhodomyrtus tomentosa (Aiton) Hassk,9
which is a perennial Myrtaceae shrub native to southern and
southeastern Asia, particularly in south China.10 The key
structural features of the two unique PPPs 5 and 6 are an
unprecedented continuous 6/6/6/5/5/6 fused rings system,
which is constituted by fusing an intriguing bisfuran-β-
triketone acylphloroglucinol scaffold with β-triketone-pyran
skeleton. Notably, the main difference of structural feature
between tomentosones A and B is the orientation of the
isobutyl side chain attached at C-7‴ position as shown in
Figure 1.
Tomentosone A exhibit significant antimalarial properties by
inhibition the growth of chloroquine-sensitive (3D7) and
resistant (Dd2) strains of the malaria parasite Plasmodium
falciparum, displaying IC50 values of 1.00 and 1.49 μM,
respectively. However, tomentosone B was found to be
significantly less active against both strains with IC50 over 40
μM, strongly indicating that the orientation of the isobutyl side
chain attached at C-7‴ plays a critical role for their
Received: September 2, 2020
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antiplasmodial activity. Moreover, tomentosone A was
suggested to be a promising antiplasmodial drug candidate
with no obvious toxicity observed even up to 40 μM.
Accordingly, their remarkable pharmaceutical activities and
novel structures make them appealing synthetic targets. In this
communication, we report the first total syntheses of
tomentosones A and B featuring potential biosynthetic
precursors and their possible sequence of segments assembly
by chemological analysis of their structural bioconstruction and
enabled to rapid access of the target molecules.
Scheme 2. Synthetic Routine for the Critical Precursors 2
and 3
On the basis of our ongoing research efforts on efficiently
accessing natural polycyclic phloroglucinols via biomimetic
pathways,11 we are intrigued by the possibility of forging the
first total syntheses of tomentosones A (5) and B (6) via a
biomimetic strategy. As outlined in Scheme 1, we tentatively
Scheme 1. Proposed Biosynthetic Pathways for
Tomentosones A (5) and B (6)
unsaturated ketone 9 was readily prepared from acylphlor-
oglucinol 12 in multigram quantities via the selective C-
methylation, retro-Friedel−Crafts acylation, and proline-
catalyzed Knoevenagel condensation reactions. The singlet
O2 Diels−Alder reaction of α,β-unsaturated ketone 9 was
further modified to generate the diastereoisomeric peroxide 8
in 35% yield through the spontaneous enolization/air
oxidation cascade reaction under room-light conditions.11f
Then, the dehydroxylation/Michael addition/Kornblum−
DeLaMare peroxide rearrangement cascade reaction was well
performed to transform peroxide 8 and acylphloroglucinol 11
into a pair of readily separated isomers 2 and 3 in good
combined yield with a ratio about 2:1.11f,12
With the synthesis of rhodomyrtosone A (2) secured, the
next task was to explore the key biosynthetic Michael addition
with the aim to install the isopentyl β-triketone fragment. As
expected, the base-mediated Michael addition processed
smoothly under room temperature to afford the critical
intermediate 7 in 92% yield. The further PTSA-mediated
intramolecular cyclization of 7 generated a pair of diaster-
eoisomers 16 and 17 with excellent yield. However, we were
surprised to find that compounds 16 and 17 shared distinctive
differences with those of tomentosones A and B (5 and 6) in
most cases of 1H and 13C NMR profiles. The further extensive
NMR spectroscopic analyses successfully established them as a
pair of regioisomers of tomentosones A and B (5 and 6), thus
giving trivial names as iso-tomentosones A and B (16 and 17)
as depicted in Scheme 3. Notably, the planar structure of iso-
tomentosone A (16) was fortunately further confirmed by
single-crystal X-ray diffraction. The generation of 16 and 17
could chemologically attribute to the superior nucleophilicity
of ortho-phenolic hydroxyl functionality of 7 because of the
strong intramolecular 1,3-hydrogen bonding effect with aryl
ketone moiety, which makes it much more electron rich than
that of the para-hydroxyl group.16
To further understand the regioselectivities between the
hydroxyl functionalities for these phenolic compounds, the
further accesses of the analogues 19 and 20 of the
tomentosones A and B through rhodomyrtosone G (3) were
then conducted. 3 was subjected to the NaH-mediated
Michael addition reaction condition, expectedly generating
the desired product 18 in 87% yield with the successful
installation of the isopentyl β-triketone fragment. The
subsequently cationic catalyzed intramolecular dehydrated
cyclization resulted in a pair of separable diastereoisomers 19
proposed that the biogenetic synthesis pathways of tomento-
sones A and B might be originated from the critical precursor
rhodomyrtone (1) or rhodomyrtosone A (2) through two
potentially alternative biosynthesis pathways. In the pathway i,
after the spontaneous enolization, the intermediate 9 could
further undergo a singlet O2 induced Diels−Alder reaction,
furnishing the key biosynthetic peroxide 8. Subsequently, the
dehydroxylation/Michael addition/Kornblum−DeLaMare per-
oxide rearrangement cascade sequence, which was previously
established by Porco and modified by our group,11f,12 would be
able to transform 8 to the natural product rhodomyrtosone A
(2).13,14 The further introduction of the β-triketone unit to the
phloroglucinol core, followed by intramolecular dehydration
cyclization, would finish the construction of tomentosones A
and B scaffold through the potential intermediate 7. Similarly,
the alternative pathway ii also shared these key biosynthetic
transformations, whereas the major difference was the priority
to construction of the β-triketone-pyran skeleton than bisfuran-
β-triketone architecture.15
With these scenarios in mind, the realization of biomimetic
total syntheses of tomentosones A and B first focused on
pathway i and commenced with the synthesis of critical
precursor rhodomyrtosone A (2) as shown in Scheme 2.
Following our previously established procedure,11a the α,β-
B
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Scheme 3. Biomimetic Total Syntheses of iso-Tomentosones
A and B (16 and 17)
Scheme 5. Biomimetic Total Syntheses of Tomentosones A
and B
and 20 with 90% combined yield. Interestingly, the formation
of 19 and 20 smoothly took placed as expected without
cleavage or rearrangement of ketal moiety, although the
bisfuran-β-triketone ring system14 was sensitive to strong acidic
reaction condition. Fortunately, both of the single crystals of
the complex products 19 and 20 suitable for X-ray diffraction
analyses (Scheme 4) were successfully obtained from ethyl
acetate solvent system, which provided conclusive evidence for
the intractable establishments of their relative configurations.
molecular dehydration cyclization in two steps with 65%
total yield. With the efficient synthesis of 23 established, the
titanium tetrachloride-mediated selective Friedel−Crafts acy-
lation could readily introduce the desired isovaleryl side chain
to offer the targeted rhodomyrtone (1) in 63% yield.
Rhodomyrtone (1) then underwent the critical dehydrox-
ylation/Michael addition/Kornblum−DeLaMare peroxide re-
arrangement cascade reaction with peroxide 8 to rapidly
accomplish the establishment of hexacyclic fused rings scaffold,
generating the expected tomentosones A and B in 73% total
yield with a ratio about 1:10. To our delight, the NMR and
HRESIMS spectra of the synthetic tomentosones A and B are
in complete agreement with those reported in the literature.
Moreover, the X-ray diffraction (XRD) analysis experiment
was also conducted for the readily crystallized synthetic
tomentosone B (6), thus unambiguously confirming its
structure and restrengthened our successful first total syntheses
of tomentosones A (5) and B (6). Their successful syntheses
also strongly suggested that the aforementioned synthetic
transformation might be probably proceeded by mimicking
their biosynthetic generations, although strong acid was
applied.
Scheme 4. Biomimetic Total Syntheses of the Analogues 19
and 20
Considering the little amount of the tomentosone A (5)
generated in the synthetic process, the intertransformation
between tomentosones A (5) and B (6) through the possible
benzofuran intermediate 24 was subsequently investigated as
shown in Scheme 6. Treating tomentosone B (6) with PTSA
could convert tomentosone B (6) into tomentosone A (5) in
nearly 10% yield (70% brsm). However, with the same
Scheme 6. Intertransformation of Tomentosones A and B (5
and 6)
The aforementioned disappointing results strongly indicated
that tomentosones A and B might be produced from natural
product rhodomyrtone (1)15,17 through the late stage
functionalization as depicted in Scheme 5. To further clarify
the possible deduction and finish the first biomimetic total
synthesis, another synthetic pathway was performed with
commercially available phloroglucinol 21. First, 23 could be
efficiently accessed through Michael addition and intra-
C
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reaction condition, 5 could be rapidly converted into 6 in 60%
yield. The aforementioned informative results collectively
pointed to that tomentosone B (6) should be a thermodynami-
cally favorable product in the equilibrium under the acidic
condition, which was also responsive for the ratio of 1:10 (5:6)
detected during the aforementioned synthetic dehydration
cyclization. The favorable generation of 6 in the equilibration
might be due to its more steric hindrance, which made it hard
to be hydrolyzed, thus resulting it as a more stable product
under the acidic condition.
In summary, the first biomimetic total syntheses of
tomentosones A and B have been achieved by chemological
analysis of their structural bioconstruction inspired by their
possible biosynthetic pathway. Our synthetic strategy primarily
relied on their potential biosynthetic precursors and the
possible sequence of segments assembly, which not only
highlighted the possible biogenetic pathways of these natural
products but also paved the way to rapidly access
tomentosones A and B and their analogues in a practical
fashion. Taking the advantage of its simplicity and efficiency,
the wide potential utility of this study would be reflected in
terms of the studies for biosynthesis, total synthesis, structure−
activity relationship, and drug development of these kinds of
natural products. The further investigations directed toward
these goals are currently underway and will be reported in due
course.
Republic of China; Guangdong Institute of Microbiology,
Guangdong Academy of Sciences, Guangzhou 510070, People’s
Republic of China; Email: liuhx@gdim.cn
Authors
Xiao Zhang − Key Laboratory of Plant Resources Conservation
and Sustainable Utilization, Guangdong Provincial Key
Laboratory of Applied Botany, South China Botanical Garden,
Chinese Academy of Sciences, Guangzhou 510650, People’s
Republic of China; Institute of Tropical Medicine, Science and
Technology Innovation Center, Guangzhou University of
Chinese Medicine, Guangzhou 510405, People’s Republic of
China
Chunmao Dong − Key Laboratory of Plant Resources
Conservation and Sustainable Utilization, Guangdong
Provincial Key Laboratory of Applied Botany, South China
Botanical Garden, Chinese Academy of Sciences, Guangzhou
510650, People’s Republic of China; Xiangya School of
Pharmaceutical Sciences, Central South University, Changsha
410013, People’s Republic of China
Guiyun Wu − Key Laboratory of Plant Resources Conservation
and Sustainable Utilization, Guangdong Provincial Key
Laboratory of Applied Botany, South China Botanical Garden,
Chinese Academy of Sciences, Guangzhou 510650, People’s
Republic of China; Institute of Tropical Medicine, Science and
Technology Innovation Center, Guangzhou University of
Chinese Medicine, Guangzhou 510405, People’s Republic of
China
Luqiong Huo − Key Laboratory of Plant Resources
Conservation and Sustainable Utilization, Guangdong
Provincial Key Laboratory of Applied Botany, South China
Botanical Garden, Chinese Academy of Sciences, Guangzhou
510650, People’s Republic of China; Guangdong Institute of
Microbiology, Guangdong Academy of Sciences, Guangzhou
510070, People’s Republic of China
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02943.
Experimental section, detailed experimental procedures,
and full spectroscopic data for all related compounds
(PDF)
Yunfei Yuan − Key Laboratory of Plant Resources Conservation
and Sustainable Utilization, Guangdong Provincial Key
Laboratory of Applied Botany, South China Botanical Garden,
Chinese Academy of Sciences, Guangzhou 510650, People’s
Republic of China
Accession Codes
CCDC 2025991, 2025993, and 2025996−2025997 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02943
Author Contributions
⊥X.Z. and C.D. contributed equally to this work.
Notes
AUTHOR INFORMATION
Corresponding Authors
■
The authors declare no competing financial interest.
Haibo Tan − Key Laboratory of Plant Resources Conservation
and Sustainable Utilization, Guangdong Provincial Key
Laboratory of Applied Botany, South China Botanical Garden,
Chinese Academy of Sciences, Guangzhou 510650, People’s
Republic of China; Xiangya School of Pharmaceutical Sciences,
Central South University, Changsha 410013, People’s Republic
of China; orcid.org/0000-0002-1652-5544;
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(no. 81773602), Natural Science Foundation of Guangdong
Province (2019A1515011694), Guangdong Special Support
Program (2017TQ04R599), Youth Innovation Promotion
Association of CAS (2020342), Frontier Science Key Program
of Chinese Academy of Sciences (no. QYZDB-SSW-SMC018),
and the Foundation of Key Laboratory of Plant Resources
Conservation and Sustainable Utilization, South China
Botanical Garden, Chinese Academy of Sciences.
Email: tanhaibo@scbg.ac.cn
Yingjie Hu − Institute of Tropical Medicine, Science and
Technology Innovation Center, Guangzhou University of
Chinese Medicine, Guangzhou 510405, People’s Republic of
China; Email: yjhu01@126.com
Hongxin Liu − Key Laboratory of Plant Resources Conservation
and Sustainable Utilization, Guangdong Provincial Key
Laboratory of Applied Botany, South China Botanical Garden,
Chinese Academy of Sciences, Guangzhou 510650, People’s
REFERENCES
■
(1) For selected reviews on phloroglucinols, see: (a) Pal Singh, I.;
Bharate, S. B. Nat. Prod. Rep. 2006, 23, 558. (b) Singh, I. P.; Sidana,
D
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Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
J.; Bharate, S. B.; Foley, W. J. Nat. Prod. Rep. 2010, 27, 393. (c) Yang,
X. W.; Grossman, R. B.; Xu, G. Chem. Rev. 2018, 118, 3508. (d) Celaj,
(15) Salni, D.; Sargent, M. V.; Skelton, B. W.; Soediro, I.; Sutisna,
M.; White, A. H.; Yulinah, E. Aust. J. Chem. 2002, 55, 229.
́
̈
(16) Morkunas, M.; Dube, L.; Gotz, F.; Maier, M. E. Tetrahedron
2013, 69, 8559.
O.; Duran, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.;
Esposito, A.; D’Abrosca, B. Phytochem. Rev. 2020, DOI: 10.1007/
s11101-020-09697-2. (e) Nicoletti, R.; Salvatore, M.; Ferranti, P.;
Andolfi, A. Molecules 2018, 23, 3370.
(17) Rhodomyrtone (1) was previously synthesized by Maier (ref
16), and we have modified its synthetic process to be more concise
and practical.
(2) For selected recent efforts on the isolation of phloroglucinols,
see: (a) Ye, Y. S.; Du, S. Z.; Jiang, N. N.; Xu, H. X.; Yang, J.; Fu, W.
W.; Nian, Y.; Xu, G. Org. Lett. 2020, 22, 6339−6343. (b) Gu, J. H.;
Wang, W. J.; Chen, J. Z.; Liu, J. S.; Li, N. P.; Cheng, M. J.; Hu, L. J.;
Li, C. C.; Ye, W. C.; Wang, L. Org. Lett. 2020, 22, 1796. (c) Vu, V. T.;
Chen, X. L.; Kong, L. Y.; Luo, J. G. Org. Lett. 2020, 22, 1380.
(d) Cheng, M. J.; Yang, X. Y.; Cao, J. Q.; Liu, C.; Zhong, L. P.; Wang,
Y.; You, X. F.; Li, C. C.; Wang, L.; Ye, W. C. Org. Lett. 2019, 21, 1583.
(e) Song, J. G.; Su, J. C.; Song, Q. Y.; Huang, R. L.; Tang, W.; Hu, L.
J.; Huang, X. J.; Jiang, R. W.; Li, Y. L.; Ye, W. C.; Wang, Y. Org. Lett.
2019, 21, 9579. (f) Hu, Y. L.; Hu, K.; Kong, L. M.; Xia, F.; Yang, X.
W.; Xu, G. Org. Lett. 2019, 21, 1007. (g) Xu, J.; Zhu, H. L.; Zhang, J.;
Liu, W. Y.; Luo, J. G.; Pan, K.; Cao, W. Y.; Bi, Q. R.; Feng, F.; Qu, W.
Org. Chem. Front. 2019, 6, 1667.
(3) Zhao, L. Y.; Liu, H. X.; Wang, L.; Xu, Z. F.; Tan, H. B.; Qiu, S.
X. J. Ethnopharmacol. 2019, 228, 50.
(4) Pham, T. A.; Hu, X. L.; Huang, X. J.; Ma, M. X.; Feng, J. H.; Li,
J. Y.; Hou, J. Q.; Zhang, P. L.; Nguyen, V. H.; Nguyen, M. T.; Xiong,
F.; Fan, C. L.; Zhang, X. Q.; Ye, W. C.; Wang, H. J. Nat. Prod. 2019,
82, 859.
(5) Xu, W. J.; Tang, P. F.; Lu, W. J.; Zhang, Y. Q.; Wang, X. B.;
Zhang, H.; Luo, J.; Kong, L. Y. Org. Lett. 2019, 21, 8558.
(6) Senadeera, S. P. D.; Lucantoni, L.; Duffy, S.; Avery, V. M.;
Carroll, A. R. J. Nat. Prod. 2018, 81, 1588.
(7) For selected papers on the applications of phloroglucinols, see:
(a) Zhao, Z. F.; Wu, L.; Xie, J.; Feng, Y.; Tian, J. L.; He, X. R.; Li, B.;
Wang, L.; Wang, X. M.; Zhang, Y. M.; Wu, S. P.; Zheng, X. H. Food
Chem. 2020, 309, 125715. (b) Vo, T. S.; Ngo, D. H. Biomolecules
2019, 9, 76. (c) Tan, H. B.; Liu, H. X.; Zhao, L. Y.; Yuan, Y.; Li, B. L.;
Jiang, Y. M.; Gong, L.; Qiu, S. X. Eur. J. Med. Chem. 2017, 125, 492.
(d) Ye, Y. S.; Li, W. Y.; Du, S. Z.; Yang, J.; Nian, Y.; Xu, G. J. Med.
Chem. 2020, 63, 1709.
(8) For selected papers on total syntheses of phloroglucinols in
recent years, see: (a) Qin, X. J.; Rauwolf, T. J.; Li, P. P.; Liu, H.;
McNeely, J.; Hua, Y.; Liu, H. Y.; Porco, J. A., Jr. Angew. Chem., Int. Ed.
2019, 58, 4291. (b) Wen, S. H.; Boyce, J. H.; Kandappa, S. K.;
Sivaguru, J.; Porco, J. A., Jr. J. Am. Chem. Soc. 2019, 141, 11315.
(c) Cheng, M. J.; Cao, J. Q.; Yang, X. Y.; Zhong, L. P.; Hu, L. J.; Lu,
X.; Hou, B. L.; Hu, Y. J.; Wang, Y.; You, X. F.; Wang, L.; Ye, W. C.;
Li, C. C. Chem. Sci. 2018, 9, 1488. (d) Guo, Y.; Zhang, Y.; Xiao, M.;
Xie, Z. Org. Lett. 2018, 20, 2509. (e) Ning, S.; Liu, Z. L.; Wang, Z. C.;
Liao, M. J.; Xie, Z. X. Org. Lett. 2019, 21, 8700.
(9) Hiranrat, A.; Mahabusarakam, W.; Carroll, A. R.; Duffy, S.;
Avery, V. M. J. Org. Chem. 2012, 77, 680.
(10) Chen, J.; Craven, L. A. Flora of China; Science Press/Missouri
Botanical Garden Press, Beijing/St. Louis, 2007; Vol. 13, p 330.
(11) (a) Liu, H. X.; Huo, L. Q.; Yang, B.; Yuan, Y. F.; Zhang, W. M.;
Xu, Z. F.; Qiu, S. X.; Tan, H. B. Org. Lett. 2017, 19, 4786. (b) Tan, H.
B.; Liu, H. X.; Chen, X. Z.; Yuan, Y. F.; Chen, K.; Qiu, S. X. Org. Lett.
2015, 17, 4050. (c) Liu, H. X.; Wang, Y.; Guo, X. Y.; Huo, L. Q.; Xu,
Z. F.; Zhang, W. M.; Qiu, S. X.; Yang, B.; Tan, H. B. Org. Lett. 2018,
20, 546. (d) Huo, L. Q.; Dong, C. M.; Wang, M. M.; Lu, X. X.; Zhang,
W. G.; Yang, B.; Yuan, Y. F.; Qiu, S. X.; Liu, H. X.; Tan, H. B. Org.
Lett. 2020, 22, 934−938. (e) Shi, L. L.; Wang, S. S.; Huo, L. Q.; Gao,
M. L.; Zhang, W. G.; Lu, X. X.; Qiu, S. X.; Liu, H. X.; Tan, H. B. Org.
Chem. Front. 2020, 7, 2385−2390. (f) Zhang, X.; Wu, G. Y.; Huo, L.
Q.; Guo, X. Y.; Qiu, S. X.; Liu, H. X.; Tan, H. B.; Hu, Y. J. J. Nat. Prod.
2020, 83, 3−7.
(12) Gervais, A.; Lazarski, K. E.; Porco, J. A., Jr. J. Org. Chem. 2015,
80, 9584.
(13) Hiranrat, A.; Mahabusarakam, W. Tetrahedron 2008, 64, 11193.
(14) Zhang, Y. B.; Li, W.; Jiang, L.; Yang, L.; Chen, N. H.; Wu, Z.
N.; Li, Y. L.; Wang, G. C. Phytochemistry 2018, 153, 111.
E
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