Synthetic investigation toward apigenin 5-: O -glycoside camellianin B as well as the chemical structure revision

Article abstract of DOI:10.1039/c6ob00655h

Capitalizing on the Au(i)-catalyzed ortho-alkynylbenzoate glycosylation method, the first total synthesis of the proposed structure of apigenin-5-O-glycoside camellianin B was achieved, wherein three approaches, one linear and two convergent, were established, through which the synthetic structures were firmly corroborated. Meanwhile, through the synthesis of anthentic camellianin B via commercially available camellianin A, the misassigned structures of camellianins A and B were revised.

Full text of DOI:10.1039/c6ob00655h

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Synthetic Investigation toward Apigenin 5-O-glycoside
Camellianin B as well as the Chemical Structure Revision
Yang Hu,a Yuan-Hong Tu,a De-Yong Liu,a Jin-Xi Liaoa and Jian-Song Sun*,a
Received 00th January 20xx,
Accepted 00th January 20xx
Capitalizing on Au(I)-catalyzed ortho-alkynylbenzoate glycosylation method, the first total synthesis of the proposed
structure of apigenin-5-O-glycoside camellianin B was acchieved, wherein three approaches, one linear and two
convergent, were established, through which the synthetic structures were firmly corroborated. Meanwhile, through the
synthesis of anthentic camellianin B via commercially availlable camellianin A, the misassigned structures of camellianin A
and B were revised.
DOI: 10.1039/x0xx00000x
www.rsc.org/
natural sources. Structurally, as the aglycon of camellianin B,
apigenin lacks the 3-hydroxyl group in comparison to
kaempferol and quercetin derivatives,9 which makes the
Introduction
Flavonoid glycosides are drawing more and more attention
from both the organic synthesis and pharmaceutical
communities, since as the major ingredients of fruits,
vegetables and beverages they have been demonstrated to
exert beneficial effect on the health of humans.1,2 Big stride
has been made in the field of flavonoid glycoside synthesis,
nevertheless, great efforts were devoted to the syntheses of
flavonoid 3-O, 7-O, 3,7-di-O, as well as C-glycosides,3 and the
synthesis of flavonol 5-O-glycosides is highly overlooked in
spite of the fact that the number of this subclass of flavonoid
glycosides is increasing rapidly and some of them have been
proved to possess interesting bioactivities.4 So far, papers
regarding flavonoid 5-O-glycosides synthesis are quite rare,
and all reported methods are heavily hinged on conventional
glycosylation methods, making the overall synthetic efficiency
far from satisfying.5 On the contrary, flavonoid 5-O-glycosides
are highly demanded not only as indispensable reference
reactivity of 5-OH dramatically decreased due to the enhanced
strength of intramolecular H-bond (IHB). As a result, the
glycosylation of apigenin 5-OH is more challenging.9 In
addition, the 1→4 linked disaccharide chain of camellianin B
further increased the synthetic difficulty because of the low
nucleophilicity of 4-OH of glucosyl residue.10 Fascinated by the
synthetic challenges as well as the possible antihyperglycemic
effect, we decided to conduct the synthetic investigation of
camellianin B, culminating in the first total synthesis of the
originally proposed structure of it via three different routes
and finally the chemical structures revision of both camellianin
B and A.
OH
3'
OH
OH
2'
1
O
8
HO
O
O
HO
R
HO
HO
HO
HO
OH
RO
compounds in flavonoid compound metabolic pathway
5c
H
O
4
5
O
HO
HO
O
O
O
O
HO
1'''
O
investigation
but also as ideal leading compounds for
1''
OH
flavonoid glycoside medicine development (Figure 1).6
OH
Camellianin B (1) R = H
Camellianin A (1') R = Ac
2
R = H, H, ( )
R = O, (3)
As typical representatives of flavonoid 5-O-glycosides,
camellianin B (1) and A (1’) were originally isolated from
Camellia sinensis L in 1987.7 Thereafter, as ingredients of
antihyperglycemic fraction extracted from Cephalotaxus
sinensis, these two glycosides were also isolated and
Figure 1. The chemical structures of representative flavonol 5-O-glycosides.
RESULTS AND DISCUSSION
characterized by Deng et al. during
a bioassay-guided
fractionation investigation.8 Although camellianin B has been
known for almost three decades, no bioactivity study has been
conducted concerning it due to its extremely low content in
Synthesis of camellianin B (1) via Linear Strategy
Given the challenges associated with apigenin 5-O-glycosidic
linkage construction, we decided to adopt a more reliable
synthetic strategy, the linear strategy, to produce camellianin
B. As implied in our precedented results, the protecting groups
on flavonol acceptors have a profound effect on the reactivity
of the 5-OHs. Thus, apigenin acceptors equipped with
hexanoyl and benzyl protecting groups were synthesized,
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which were directly realized by controlling the equivalents of Upon subjected to conventional acid-promoted reductive
the employed reagents, furnishing 4a and 4b in 76% and 68%, conditions (TFA, Et3SiH),15 the cleavage of glycosidic linkage
respectively (Scheme 1).
competed with the desired reductive opening process to yield
the decomposed by-products. To avoid exposure of the
vulnerable apigenin 5-O-glycosidic linkage to harsh acidic
conditions, mild reaction conditions were also tried (Cu(OTf)2,
Me2EtSiH),16 but no reaction was detected and the starting
material was recovered quantitatively. Because efforts to
realize the desired benzylidene reductive opening all met with
failure, the direct route was abandoned and a detour was
adopted in which thoroughly removal of benzylidene group
and regioselective protection of the primary 6’’-OH were
entailed. After extensive tries, the optimal conditions for
thorough removal of benzylidene group of 9 were fixed, that is,
5.0 equivalents of TFA, 8.0 equivalents of EtSH, and catalytic
amounts of BzCl (0.002 equiv.) at 0 oC (see table 1). Under
Scheme 1. Synthesis of acceptors 4a and 4b
.
these conditions, the benzylidene group in
9 was rapidly
1
Interestingly, careful scrutiny of the H NMR spectra of 4a and
4b shown that apigenin 5-OH acceptor with electron-
withdrawing protecting groups on 7,4’-OHs had weakened IHB
than that of compound carrying electron-donating protecting
groups, as demonstrated by the chemical shifts of apigenin 5-
OH protons (for 4a the proton appeared at 12.68 ppm whereas
the corresponding proton for 4b resonated at 12.80 ppm). The
chemical shift of hydroxyl protons involved in formation of IHB
is a reliable indicative for the strength of the corresponding
IHB,11 and for flavonoid derivatives reduced IHB strength can
facilitate the glycosylation of 5-OH. In consequence, 4a was
chosen as acceptor in the following synthetic study.
removed, and the diol intermediate 10 was isolated in a good
83% yield. Selective blocking of the primary 6’’-OH of the sugar
residue was achieved by treatment of 10 with BzCl at low
temperature to afford 11 which is ready for subsequent
rhamnosyl moiety installation. The introduction of benzoyl
group on the 6’’-OH was determined by the down-field shifts
of H’’-6 protons from 3.98 ppm to 4.67 ppm.
With easily available intermediate 512 as starting material,
the synthesis of glucosyl ortho-alkynylbenzoate
8 and its
application in the pivotal glycosidic linkage construction were
depicted in scheme 2. Thus, treated with TDSCl and imidazole,
the anomeric OH of
high regio- and stereo-selectivity, yielding
(82%).10a The remaining free 2-OH in
was then protected as
benzoyl ester so as to ensure the stereoselectivity via
anchimeric effect in the ensuing glycosylation step to give
(91%). HF•pyridine mediated removal of the anomeric TDS of
was followed by esterification of the nascent OH under
dehydrative conditions to generate glucosyl ortho-
alkynylbenzoate donor (66%, 2 steps). With both donor
5
could be blocked as TDS silyl ether with
6
efficiently
6
Scheme 2. Synthesis of apigenin 5-O-monoglycoside acceptor 11
.
7
Debenzylidenation is
protecting group manipulation perspective. Nevertheless, in
the case of , to remove it without touching the acid-sensitive
apigenin 5-O-glycosidic linkage is by no way a trivial problem.
Considering that the successful debenzylidenation of could
a relatively simple process from
7
9
8
8
and acceptor 4a in hand, the challenging glycosylation was
9
then tried under the promotion of catalytic amount of Au(I)
complex.13 Pleasantly, a respectable 61% yield of
not only facilitate the total synthesis of the target molecule
but also offer helpful reference to practioners who will
conduct the same transformation on acid-susceptible
substrates, we decided to investigate this reaction
systematically (Table 1). During the investigation the direct
reductive benzylidene opening reaction, we observed that the
glycosidic linkage was limited stable to acidic conditions and
9
was
isolated, even though donor
8 suffered from diminished
reactivity due to the ‘torsional effect’ exerted by 4,6-O-
benzylidene protecting group. Only β-isomer was detected, as
determined by the anomeric proton of the glucosyl residue
(5.47 ppm, J = 7.2 Hz). The sugar attachment position was
corroborated by NOE spectrum, which clearly shown that H’’-1
had correlation only with one of the two protons assigned to
the maximum tolerant amount to TFA for
9 was determined to
be 5.0 equivalents; once the applied TFA amounts exceeded
5.0 equivalents, the decomposition side reaction became
o
serious. Thus, TFA (5.0 equiv.) in dry CH2Cl2 at 0 C was tried
H-6 and H-8.14 With considerable amount of
9 being available,
our attention was then turned to the following acid-catalyzed
regioselectively reductive opening of the benzylidene group in
first, and after 4 h of stirring, only 30% yield of 10 was
9. Unexpectedly, this conversion was proved to be extremely
obtained, and the remaining
9 was recovered (entry 1).
problematic due to the acid-sensitivity of the glycosidic linkage.
Prolonging the reaction time could not bring about evident
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improvement. To expedite the desired process, TFA (5.0 equiv.) and catalyst simultaneously is widely adopted strategies to
water was tried as nucleophilic species in the presence of TFA conquest inert glycosylation acceptors.20 Thus, under the
(5.0 equiv.) at room temperature, but an even lower yield of effect of either 0.2 or 0.4 equivalents of PPh3AuNTf2, 12 in
10 was recorded (entry 2). In this case, the extended reaction great excess (3.0 equiv.) were then tried to react with 11
time was detrimental to the desired deprotection process (entries 2 and 3); again, no promising result was obtained.
because of evident glycosidic linkage fracture. Replacing TFA Further screening entailed resorting to more powerful catalyst
with stronger TsOH at the presence of water led to the loss of PPh3AuOTf,13a,15b however, besides considerable amounts of
the Hexanoyl group on 7-OH of apigenin residue and only trace decomposition of 11 (0.4 equivalents of Au(I) complex), no
amount of 10 was detected (entry 3).9 Logically, weaker acids desired glycosylation product were detected (entries 4 and 5).
18
including HOAc17 and Er(OTf)3 were then checked, but these Finally, super-armed donor 1314,19 was invoked, and pleasantly
efforts were finally proved to be futile (entries 4-6). In view of we were rewarded by a promising yield of 15% disaccharide 14
the fact that only TFA provided promising results, we decided under the promotion of PPh3AuNTf2 (entries
6 and 7).
to fix TFA as the acid of choice while continued to screen other Switching the catalyst from PPh3AuNTf2 to PPh3AuOTf brought
nucleophilic reagents besides water. Fortunately, EtSH (8.0 about a dramatic enhancement in chemical yield, and 91%
equiv.) was found to be the best of choice, and under the yield of 14 was isolated (entry 8). The structure of 14 was
promotion of TFA (5.0 equiv.) it could afford the desired determined by 1H and 13C NMR spectra (For anomeric protons:
debenzylidene product 10 in a good 81% yield (entry 7). H-1’’ resided at 5.51 ppm with J value being 6.0 Hz, whereas H-
Although the chemical yield was satisfying, the reaction was 1’’’ resided at 5.21 ppm in a doublet form with J = 2.0 Hz; For
sluggish, and at least 4.5 h were required before the reaction anomeric carbons: C-1’’ and C-1’’’ had chemical shifts of 99.3
reached completion. Serendipitously, catalytic amount of BzCl and 97.7 ppm, respectively).
(0.002 equiv) was demonstrate to be beneficial to the
Table 2. Optimization of conditions to form apigenin 5-O-disaccharide.
deprotection process, and at the presence of it the reaction
time was shortened drastically to 45 min while the yield was
maintained at above 80% (entry 8). The accelerating effect of
BzCl was ascribed to the trace amount of HCl generated in situ
by the reaction between BzCl and EtSH, which could easily
activate the oxygen of the benzylidene group.
Table 1. Optimization of the conditions to remove benzylidene group in 9.
a Isolated yield. b NR = no reaction.
With apigenin 5-O-disaccharide 14 in hand, all it took to
reach
1 was the global deprotection (Scheme 3). To this end,
14 was subjected to palladium mediated hydrogenolysis and
base mediated saponification successively, after purification by
C18 RP chromatography, to afford
It should be pointed out that the sequence of the deprotection
steps is crucial for the success of producing , since reversed
1 successfully (76%, 2 steps).
1
deprotection sequence only afforded a complicated mixture. It
is also worth mentioning that in the debenzylation step CH2Cl2
is an indispensable solvent ingredient, because without it the
debenzylation reaction became extremely sluggish.
a
b
c
d
Isolated yield; TFA (5.0 equiv. to 9); TFA (5.0 equiv.), EtSH (8.0 equiv.); TFA (5.0
equiv.), EtSH (8.0 equiv.), BzCl (0.002 equiv.).
The optimized debenzylidenation conditions could afford 10
efficiently and reproducibly, paving the way to get diol 10
easily and in turn the monoglycoside acceptor 11. With 11 in
hand, the following rhamnosyl residue incorporation was then
investigated. Not unexpectedly, the extremely inert property
of acceptor 11 toward glycosylation posed another hurdle en
Subsequently, comparison of the spectra of synthetic
1 with
those reported in literature7,8 was conducted, and
unfortunately evident discrepancies were observed. More
surprisingly, regarding the target molecule camellianin B,
different documents provide contradictory analytic data (see
ESI for 1H NMR data comparison with different origins).
Therefore, the reported data could not be used as convincing
reference to judge the chemical structure obtained via
chemical synthesis is right or not, and further measures have
to be taken before a conclusion could be formed.
route to produce
1
(Table 2). Easily available donor 1219 (1.2
equiv.) was tried first to condense with 11 under the
promotion of PPh3AuNTf2 (0.2 equiv.). Surprisingly, no desired
rhamnosylation product was detected and acceptor 11 was
recovered completely (entry 1). Increasing the donor
equivalents solely or enhancing the amounts of both donor
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convergent route, disaccharide 16 was not immediately
transformed to disaccharide donor, instead, protecting groups
unification was performed first. Thus, debenzylation of 16 via
palladium-catalyzed hydrogenation furnished diol 19 (90%).
The accelerating effect of CH2Cl2 on hydrogenolysis process
was once more detected and utilized. Surprisingly, the free 3-
OH in 19 was so inert that conventional benzoylation
Scheme 3. Completion the synthesis of the proposed camellianin B (1).
o
conditions (BzCl, pyridine, 0 C to rt) could not benzoylate it,
Synthesis of camellianin B (1) via Convergent Strategy
and only 6-OH benzoylated intermediate was isolated.
Eventually, harsher reaction conditions were adopted, and the
desired perbenzoylated disaccharide 20 was obtained
successfully in 92% yield, which was then converted to
disaccharide donor 21 without any event. Under the catalysis
of Ph3PAuNTf2, 4a was fluently glycosylated with donor 21 to
afford apigenin 5-O-disaccharide 22 (46%). At this junction, the
structure of 22 was thoroughly analysed through 1D and 2D
NMR spectra. The sugar chain attachment position was
definitely confirmed by NOE correlation between H-1’’ and H-6
(6.82 ppm, d, J = 2.0 Hz) as well as by HMBC correlation of H-1’’
and C-5. C-5 (156.2 ppm) was discriminated easily by its strong
HMBC correlation with H-6, while the corresponding
correlation with H-8 (6.96 ppm, d, J = 2.0 Hz) was not detected.
If the same compound as that generated via linear strategy
could also be obtained by convergent strategy, then this would
provide a convincing evidence to verify the correctness of the
chemical structure of the synthetic
1. Meanwhile, the
convergent approaches may avoid the drawbacks inherent to
linear route, thereby providing the proposed camellianin B in a
more efficient manner. To this end, two convergent synthetic
routes have been devised, and the first one is depicted in
scheme 4. Thus, treated with TFA and Et3SiH, the benzylidene
group in
excellent yield, although the same transformation on
frustrating in the linear approach. Regarding acceptor 15
7
was reductively opened efficiently, yielding 15 in
9
was
,
because the due to glycosylated 4-OH was flanked by two
electron-donating benzyl groups at both 3 and 6-OHs and the
The 1→4 inter-sugar linkage pattern of the disaccharide chain
adverse effect exerted by the bulky apigenin moiety (cf. 11
)
was deduced by strong HMBC correlations between H-1’’’
1
(5.34 ppm, d, J = 1.6 Hz, assigned by H NMR) and C-4’’ (75.7
was removed, the reactivity was so high that even disarmed
rhamnosyl donor 12 could couple with it to furnish
disaccharide 16 in 92% yield. The resultant 16 was then
subjected to HF•pyridine mediated desilylation and
dehydrative o-alkynylbenzoylation successively to produce
disaccharide donor 17 (80%, 2 steps). The pivotal glycosylation
between donor 17 and acceptor 4a proceeded fluently to give
18 in a venerable 48% yield. The structure of 18 was confirmed
by both 1H NMR spectrum wherein H’’ and H’’’ protons
ppm, deduced by its HMQC correlation with H-4’’ resonating at
4.91 ppm as a triple signal with a J value of 9.2 Hz which could
be easily discriminated by 1H NMR), as well as HMBC
correlation of C-1’’’ (assigned by HMQC at 98.9 ppm) and H-4’’
(Scheme 5).14 Therefore, the structure of 22 was confidently
confirmed. All it takes from 22 to reach
protecting groups under basic conditions. Thus, treated with
NaOMe, 22 was converted to in an as high as 95% yield.
Again, the obtained was proved to be identical to those
obtained by the former two approaches.
1 is removal of all acyl
1
appeared at 5.46 (d, J = 6.4 Hz) and 5.32 (d, J = 1.6 Hz) and 13
C
1
spectrum in which the anomeric carbons of C-1’’ and C-1’’’
resonated at 97.3 and 100.1 ppm, respectively. Finally, similar
deprotection procedures as those used for compound 14 was
applied to 18, and identical product 1 was produced, as
verified by both TLC and 1H NMR spectrum.
Scheme 4. Convergent synthesis of 1 with 17 as donor.
Scheme 5. Convergent synthesis of 1 with 21 as donor.
To further simplify the post-glycosylation manipulations and
improve the convergent extent, the more convergent
approach wherein disaccharide donor 21 equipped with
unified acyl protecting groups was applied was subsequently
investigated (Scheme 5). Distinct from the above mentioned
Revision of the originally proposed chemical structures of
camellianin B and A
Although the fact that all synthetic routes resulted in the
same product provides a strong support for the correctness of
our synthetic compound, problems leading the spectroscopic
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discrepancies between synthetic and authentic samples should wherein the challenging apigenin 5-O-glycosidic linkages were
be specified. Although the two reported analytic data of are fashioned with disaccharide ortho-alkynylbenzoites as donors
conflicting to each other, consensus is reached in terms of the under the catalysis of Au(I) complex. All three routes yielded
relationship between camellianin B ( ) and A ( ’), that is, the same products, verifying the correctness of the synthetic
1
1
1
camellianin B differentiates from A by losing the acetyl group compound. The evident discrepancies of spectroscopic data
on 6’’-OH of glucose residue. Hence, the authentic camellianin between those of synthetic sample and those reported in
B could be obtained by deacetylation of the commercially literature coupled with the contradictory published analytic
available camellianin A (Scheme 6).21 Treated with NaOMe, data concerning
camellianin was fluently converted to the authentic well as peracetlylated authentic target molecules, which
1 prompted us to synthesize the authentic as
A
camellianin B (91%). Spectroscopic analysis revealed that the eventually led to the final structure revision of camellianin B
authentic camellianin B was not identical to those obtained by and A.
chemical synthesis (the NMR comparison between the
synthetic and authentic samples is provided in ESI). To
Acknowledgements
facilitate the reassignment of the chemical structures of
camellianin B and A, peracetylation of authentic was
1
This work was financially supported by the National Science
Foundation of China (21572081 and 21372252) and the
Starting Foundation for Doctors of Jiangxi Normal University.
performed under conventional conditions (98% yield), and the
resultant peracetylated camellianin B was then subjected to
thoroughly 1D and 2D NMR analysis. The NOE correlation peak
between H-6 and H’’-1 indicated that the sugar chain was
indeed attached to the 5-OH of the apigenin moiety; while the
H-H COSY correlation between H’’-1 and H’’-2 which resided at
Notes and references
1
a) J. B. Harborne and C. A. Williams, Nat. Prod. Rep. 1995, 12,
4.22 ppm implied that the sugar chain was 1→2 linked instead
639-657. b) J. B. Harborne and C. A. Williams, Nat. Prod. Rep.
1998, 15, 631-652. c) J. B. Harborne and C. A. Williams, Nat.
Prod. Rep. 2001, 18, 310-333. d) N. C. Veitch and R. J. Grayer,
Nat. Prod. Rep. 2008, 25, 555-611.
of the originally proposed 1→4 linked. This linkage pattern
was further corroborated by HMBC spectrum, wherein the
correlations of H-1’’’ and C-2’’, H-2’’ and C-1’’’, as well as H-2’’
and C-1’’ were recognized. Therefore, the architecture of
peracetlated camellianin B should be revised to that shown in
the red panels of scheme 6, in turn both the chemical
2
3
J. B. Harborne and H. Baxter, The Handbook of Natural
Flavonoids; John Wiley & Sons: Chichester, UK, 1999, Vol. 1.
For reviews of flavonoid glycosides synthesis, see: a) K.-i.
Oyama, K. Yoshida and T. Kondo, Curr. Org. Chem. 2011, 15
,
2567-2607. b) O. Talhi and A. M. S. Silva, Curr. Org. Chem.
2012, 16, 859-896. c) J. Sun, S. Laval and B. Yu, Synthesis
2014, 1030-1045.
structures of camellianin
incorrectly.
B and A have been assigned
4
5
a) B. S. Siddiqui, N. Khatoon, S. Begum, A. D. Farooq, K.
Qamar, H. A. Bhatti and S. K. Ali, Phytochemitry 2012, 77,
238-244. b) S. Perveen, A. M. Al-Taweel, N. Al-Musayeib, G.
A. Fawzy, A. Khan, R. Mehmood and A. Malik, Nat. Prod. Res.
2015, 29, 615-620.
a) J. A. Mahling and R. R. Schmidt, Synthesis 1993, 325-328.
b) B. Alluis and O. Dangles, Helv. Chim. Acta 2001, 84, 1133-
1136. c) M. Kajjout and C. Rolando, Tetrahedron 2011, 67
,
4731-4741. d) W. Yang, R. Li, W. Han, W. Zhang and J. Sun,
Chin. J. Org. Chem. 2012, 32, 1067-1071.
6
7
8
H.-Y. Hung, K. Qian, S. L. Morris-Natschke, C.-S. Hsu and K.-H.
Lee, Nat. Prod. Rep. 2012, 29, 580-606.
G. Cheng, J. Jin and Y. Wen, Acta Pharmaceutica. Sinica 1987,
22, 203-207.
W. Li, R.-J. Dai, Y.-H. Yu, L. Li, C.-M. Wu, W.-W. Luan, W.-W.
Scheme 6. Synthesis of authentic and peracetylated authentic camellianin B
Meng, X.-S. Zhang and Y.-L. Deng, Biol. Pharm. Bull. 2007, 30
1123-1129.
J.-X. Liao, N.-L. Fan, H. Liu, Y.-H. Tu and J.-S. Sun, Org. Biomol.
Chem. 2016, 14, 1221-1225.
,
CONCLUSION
9
The first total synthesis of proposed camellianin B was
achieved via three different routes. In the first route, a linear
tactic was adopted. Although the early introduced acid-labile
apigenin 5-O-glucosidic linkage made the following protecting
group manipulations and sugar chain elongation quite difficult,
all associated problems were overcome via systematic
optimizations. In particular, efficient approaches to remove
benzylidene protecting group of acid-sensitive substrate and to
construct glycosidic linkage of inert acceptor containing
flavonoid moiety were established. To avoid the problems
posed by the existence of susceptible apigenin 5-O-glycosidic
linkage, another two convergent routes were also devised,
10 As glycosyl acceptors, the reactivity of 4-OH of glucosyl
residues are low. For selected examples, see: a) O. P.
Dhamale, C. Zong, K. Al-Mafraji and G.-J. Boons, Org. Biomol.
Chem. 2014, 12, 2087-2098. b) S. Das, D. Pekel, J.-M.
Neudorfl and A. Berkessel, Angew. Chem. Int. Ed. 2015, 54
,
12479-12483. c) H. Tamai, A. Imamura, J. Ogawa, H. Ando, H.
Ishida and M. Kiso, Eur. J. Org. Chem. 2015, 5199-5211.
11 P. Uhlmann and A. Vasella, Helv. Chim. Acta 1992, 75, 1979-
1994.
12 M. Nitz and D. R. Bundle, J. Org. Chem. 2001, 66, 8411-8423.
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21 Authentic camellianin A was purchased from Chengdu Push
Bio-technology Co. LTD (Http://www.push-herbchem.com),
the spectra performed in MeOH-d6 were also provided at
the same time by the company. After we received the
sample, H NMR was also made and the obtained spectrum
is identical to that provided by the company.
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