Bioinspired Total Synthesis of (?)-Vescalin: A Nonahydroxytriphenoylated C-Glucosidic Ellagitannin

Article abstract of DOI:10.1002/anie.201707613

The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (?)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg–Feringa–Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (?)-vescalin.

Full text of DOI:10.1002/anie.201707613

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Bio-inspired Total Synthesis of (-)-Vescalin, A Nonahydroxy-
triphenoylated C-Glucosidic Ellagitannin
Authors: Antoine Richieu, Philippe A. Peixoto, Laurent Pouységu,
Denis Deffieux, and Stephane Quideau
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201707613
Angew. Chem. 10.1002/ange.201707613
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10.1002/anie.201707613
Angewandte Chemie International Edition
COMMUNICATION
Bio-inspired Total Synthesis of (–)-Vescalin, A Nonahydroxy-
triphenoylated C-Glucosidic Ellagitannin
Antoine Richieu, Philippe A. Peixoto, Laurent Pouységu, Denis Deffieux,* and Stéphane Quideau*
In memoriam Professor Takuo Okuda
Abstract: The first total synthesis of the 2,3,5-O-(S,R)-
NonaHydroxyTriPhenoylated (NHTP) C-glucosidic ellagitannin (–)-
vescalin was accomplished through a series of transformations
mimicking the sequence of events leading to its biogenesis. The key
steps of this synthesis encompass a Wittig-mediated ring opening of
a glucopyranosic hemiacetal, a C-glucosidation event via a phenolic
aldol-type reaction, and a Wynberg–Feringa–Yamada-type oxidative
phenolic coupling, which forged the NHTP unit of (–)-vescalin.
could then react together in a phenolic aldol-type reaction
manner to forge the characteristic C-arylglucosidic bond.
HO
HHDP unit
HO
OH
C-arylglucosidic
bond
HO
S
OH
O
HO
2
β-OH ⇒ (–)−vescalagin (3)
α-OH ⇒ (–)−castalagin (4)
O
3
5
1
OH
OH
HO
HO
O
O
O
4
O
O
O
HO
HO
OH
O
6
O
O
R
S
O
NHTP unit
O
O
OH
OH
HO
HO
O
HO
HO
OH
OH
O
R
(–)-Vescalin (1) is a member of the C-glucosidic ellagitannin
subclass of gallic acid-derived polyphenolic secondary
metabolites[1] that are produced by dicotyledonous plant species
of the Angiospermea, and in particular by some of the more
highly evolved species belonging to the Rosidae, Hamamelidae
and Dilleniidae subclasses.[2] (–)-Vescalin (1) was first isolated
from Quercus (oak) and Castanea (chestnut) species of the
Fagaceae family (Hamamelidae), together with its α-epimer (+)-
castalin (2) and their congeners (–)-vescalagin (3) and (–)-
castalagin (4) (Figure 1).[3] The double axially chiral 2,3,5-O-
nonahydroxytriphenoyl (NHTP) unit, also referred to as the
flavogallonyl unit,[1b] is the special structural feature of these
ellagitannins, which are otherwise typified by their glucose core
in an open-chain form and their C-arylglucosidic bond.[1c] Since
their first structural characterization fifty years ago by Mayer and
his colleagues,[3] the assignment of the configuration of their C-1
center was revised in 1990 by Nishioka and his colleagues,[4a]
and the atropisomerism of their terarylic NHTP unit was very
recently revised by Tanaka’s group (Figure 1).[4b]
S
HO
OH
HO
HO
OH
OH
β-OH ⇒ (–)−vescalin (1)
α-OH ⇒ (+)−castalin (2)
HO
Figure 1. Chemical structures of vescalin (1) and its fagaceous congeners.
This chemical event would lead to the formation of the epimeric
stachyurin (7) and casuarinin (8).[4a,7d,8] An enzymatically-
induced oxidative coupling between their 5-O-galloyl and 2,3-O-
HHDP groups would furnish vescalagin (3) and castalagin (4).
The 4,6-O-HHDP unit of these epimers would be hydrolytically
cleaved off, perhaps via the catabolic action of a tannin acyl
hydrolase (i.e., tannase),[3a,9] to generate vescalin (1) and
castalin (2) (Scheme 1).
OH
OH
HO
HO
HO
HO
HO
HO
S
S
O
O
O
O
ring opening
5-O-galloylation
O
O
5
5
O
O
OG
O
O
O
HO
HO
HO
HO
HO
HO
HO
O
O
+G
1
1
OH
O
O
O
Despite the uniqueness of these natural products, albeit
occurring in many common plant species, very little is known
about their biogenesis, and only hypothetical proposals have
been discussed in the literature on the basis of phytochemical
observations and isolation of key precursors made by Okuda’s
group,[5] as well as thoughts and exploration on/of the chemical
reactivity of putative intermediates.[6] Accordingly, all of the C-
glucosidic ellagitannins could derive from the ellagitannin
pedunculagin (5),[7] whose glucopyranosic ring is subjected to
opening in aqueous media (Scheme 1). The resulting free
hydroxy group at C-5 would be enzymatically galloylated to
generate the open-chain aldehyde liquidambin (6), which was
isolated by Okuda’s group in 1987 from Liquidambar formosana
of the Hamamelidaceae family (Hamamelidae).[5b] The aldehyde
function and the 2,3-O-hexahydroxydiphenoyl (HHDP) unit of 6
HO
O
O
S
S
G = 3,4-5-trihydroxybenzoyl
HO
HO
liquidambin (6)
pedunculagin (5)
HO
HO
OH
C-aryl-
OH
OH
HO
HO
OH
OH
HO
S
O
HO
glucosidation
O
O
O
HO
2
3
5
OH
OH
6
4
β-OH ⇒ vescalagin (3)
α-OH ⇒ castalagin (4)
oxidative coupling
O
1
OG
O
O
O
tannase ? – 4,6-HHDP
β-OH ⇒ stachyurin (7)
α-OH ⇒ casuarinin (8)
S
OH
β-OH ⇒ vescalin (1)
α-OH ⇒ castalin (2)
OH
OH
HO
HO
Scheme 1. Putative biosynthetic pathway to vescalin (1) and related C-
glucosidic ellagitannins.
These metabolism considerations had fuelled our earlier work
that led to a biomimetic synthesis of a first member of the C-
glucosidic ellagitannin group, the 2,3-O-(S)-HHDP-bearing 5-O-
[*]
A. Richieu, Dr. P. A. Peixoto, Prof. L. Pouységu, Dr. D. Deffieux,
Prof. S. Quideau
Univ. Bordeaux, ISM (CNRS-UMR 5255)
351 cours de la Libération, 33405 Talence Cedex (France)
E-mail: denis.deffieux@u-bordeaux.fr,
desgalloylepipunicacortein
A
(9, Scheme 2).[10] This initial
success laid some of the groundwork for the next and primary
challenge of accomplishing the chemical synthesis of a terarylic
NHTP-bearing C-glucosidic ellagitannin. Herein, we thus
stephane.quideau@u-bordeaux.fr
Supporting information of this article can be found under:
http://dx.doi.org/…
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10.1002/anie.201707613
Angewandte Chemie International Edition
COMMUNICATION
describe the first total synthesis of (–)-vescalin (1), which is
moreover known for exhibiting valuable biological activities
notably as a potent inhibitor of human DNA topoisomerase IIα in
vitro,[11a,b] and as an anti-actin agent in cellulo.[11c] Its natural
abundance in fagaceous species is highly variable and rather
low (ca 0.1-1.5 mg/g of dry oak wood),[12a] although it can be
obtained by acidic hydrolysis of vescalagin (3),[3a,11a] which is
much more abundant (ca 10-15 mg/g of dry oak wood, up to >
40 mg/g of dry chestnut wood)[12] and readily extractable in
gram-scale quantities.[3a,11a,13] Our main incentive for selecting (–
)-vescalin (1) as a target of choice for total synthesis work was
to elaborate a tactic for the atroposelective construction of its
NHTP unit, which constitutes the last remaining major milestone
for the chemical synthesis of the series of natural products to
which 1 belongs.[10b,14] The added difficulty that we imposed on
ourselves was to follow the current biosynthesis hypotheses
(Scheme 1) as blueprints to develop a synthesis strategy relying
on the same sequence of key chemical events.
(Scheme 2). Thus, our synthesis began with the 3-step
conversion of this commercial glucopyranosyl bromide into the
ortho-nitrobenzyl 4,6-O-benzylidene-β-D-glucopyranoside 10
(Scheme 3), which was bisacylated with the orthogonally
protected gallic acid 11, as previously described (see the
Supporting Information).[10b] The Steglich-type bisacylation was
followed by a TBAF-mediated desilylation to afford the E-type
2,3-O-digalloylated glucopyranoside 12 in 91% yield from 10.
1. o-NO2BnOH, Ag2CO3, cat. I2, CH2Cl2
AcO
O
Ph
2. cat. MeONa, MeOH
3. PhCHO, ZnCl2
O
O
AcO
AcO
O
OBn(o-NO2)
OH
HO
2
3
AcO
OH
O
Br
Ph
10 80%
O
O
O
1. EDCI HCl, DMAP,
OBn(o-NO2) CH2Cl2
2. TBAF, AcOH, THF
O
O
O
2
TBSO
OTBS
3
OBn
OH
12 91%
O
11 75% from methyl
gallate
HO
OH
OBn
OBn
OH
CuCl2 (5 equiv), amine (20 equiv),
MeOH, rt, 10 to 30 min
C-aryl-
glucosidation
O
O
O
Ph
Ph
5
O
O
P1O
O
OH
OH
OP1
HO
HO
2
2
HO
TBSO
2
OBn(o-NO2)
O
O
2
3
1
5
1
3
3
OH
OH
OH
OH
5
OH
OH
5
3
1
OH
O
O
O
O
1. TBSOTf, DMAP, Et3N, CH2Cl2
2. hν (350 nm), EtOH/THF/H2O
O
O
O
BnO
BnO
1
O
O
O
O
OH
O
O
O
O
O
O
O
S
HO
HO
O
O
O
amine ⇒ 13
HO
HO
TBSO
TBSO
14 77%
O
R
OTBS
n-BuNH2 ⇒ 58%
bispidine ⇒ 48%
(–)-sparteine ⇒ 68%
S
S
S
OBn
OH
OTBS
OP1
HO
OH
OH
pG
OH
OH
OH
HO
OH
OH
OH
OH
OBn
O
OBn
over 2 steps
OH
HO
O
P1O
HO
OTBS
CO2Et
O
Ph
OP1
5
HO
HO
atroposelective
oxidative coupling
O
A
vescalin (1)
TBSO
O
5-O-desgalloyl-
epipunicacortein A (9)
1
diastereoselective
phenolic aldol
O
O
BnO
O
1. Ph3PCHCO2Et, TFE, PhMe
2. 11, EDCI HCl, DMAP, CH2Cl2
ring opening
P1O
P1O
P1O
P1O
P1O
15 83%
over 2 steps
TBSO
5
5
O
OpG
OpG
P1O
P2O
P1O
P2O
P1O
P2O
P1O
O
O
O
O
CO2R
TBSO
OTBS
2
2
3
3
O
1
1
OH
O
1
Ph
OpG
O
O
O
O
O
OBn
O
O
O
S
O
O
TBSO
oxidative
cleavage
O
Wittig
1
5-O-galloylation
O
O
P2O
P2O
OP2
P2O
P2O
P2O
BnO
O
16 82% using
Pb(OAc)4
1. cat. OsO4, NMO, 2,6-lutidine,
dioxane/H2O
OP2
OP2
OP2
TBSO
OP1
OP1
OP1
D
C
B
atroposelective
oxidative coupling
2. Pb(OAc)4, NaHCO3, CH2Cl2
or PhI(OAc)2, CH2Cl2
TBSO
OTBS
OBn
P1O
P1O
pG = protected 3,4-5-trihydroxybenzoyl
P1, P2 = orthogonal protective groups
R = alkyl, benzyl groups
O
O
Scheme 3. Synthesis of a liquidambin-like precursor of vescalin (1).
OR
O
O
2
3
AcO
O
AcO
OH
O
The reason why we opted for para-benzylated galloyl groups is
because this partial protection enables to direct the reactivity of
galloyl groups toward the desired oxidative coupling using
copper(II)-amine complexes under anaerobic conditions, as per
the recommendation of Feringa and Wynberg.[15] The
intramolecular oxidative coupling of para-benzylated galloyl
groups was first implemented under such conditions by Yamada
and his co-workers, who successfully applied it in the total
AcO
HO
OH
AcO
OP1
OH
Br
OP1
E
Scheme 2. Retrosynthetic analysis of vescalin (1).
Our retrosynthetic analysis depicts this strategy (Scheme 2), for
which the focal oxidative coupling step leading to the
intramolecular formation of the nonahydroxyteraryl unit is
planned at a very late stage of the synthesis and with a control
of the desired atroposelectivity solely relying on the chirality of
the substrate. This substrate (A), which will have to be
appropriately protected for the success of the intended oxidative
phenolic coupling, features the characteristic C-arylglucosidic
bond. This bond will be forged from an aldehydic liquidambin
analogue B through a biomimetic phenolic aldol-type reaction.
This key aldehyde will be obtained by oxidative cleavage of an
olefinic ester C, which will be generated by a classical Wittig
reaction on a glucopyranosic hemiacetal D, followed by a 5-O-
synthesis
of
several
glucopyranosic
HHDP-bearing
ellagitannins.[16] We also relied on the same method to forge a
D-type 2,3-O-(S)-HHDP-bearing intermediate in the synthesis of
the C-glucosidic ellagitannin 9.[10b] Here, 12 was initially treated
with CuCl2 and a large excess of n-BuNH2 in freshly distilled
MeOH at room temperature for 30 min to furnish the desired (S)-
biaryl 13 as the sole atropisomer in 58% isolated yield (see
Table S1 in the Supporting Information). Its silylation had to be
performed using excesses of TBSOTf (10 equiv) and Et3N (20
equiv) in the presence of DMAP (1 equiv) in refluxing CH2Cl2 for
6 h to afford the desired tetrasilylated product, which was then
irradiated at 350 nm for 48 h to furnish the D-type glucopyranose
14 in 77% yield over these two steps. Unlike the synthesis of 9,
galloylation. The 2,3-O-(S)-HHDP-bearing glucopyranose
D
could be generated from a 2,3-O-digalloylated precursor E, itself
prepared from tetra-O-acetyl-α-D-glucopyranosyl bromide
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10.1002/anie.201707613
Angewandte Chemie International Edition
COMMUNICATION
for which the opening of analogous D-type glucopyranoses was
a transient transformation during the formation of the C-
arylglucosidic bond,[10b] this synthesis of 1 required access to an
open-chain glucose derivative that could be sequentially
amenable to the 5-O-galloylation and C-arylglucosidation events
(Scheme 2). We opted for a Wittig olefination to force the
opening of the glucopyranose ring, which is a tactic that was
successfully employed by Yamada’s group for the passage from
4C1 to 1C4 conformations of glucopyranosic intermediates in their
synthesis of the ellagitannin corilagin.[16a,17] Thus, after a few
experimentations (see Table S2 in the Supporting Information),
the use of the conjugated phosphorane PPh3CHCO2Et in the
presence of trifluoroethanol (TFE, 2 equiv) in anhydrous toluene
(Vilarrasa’s conditions)[18a] was found to efficiently promote the
conversion of the cyclic hemiacetal 14 into the expected open-
chain olefinic ester (E/Z = 8:2), which was 5-O-galloylated using
11 under Steglich-type conditions to furnish the C-type olefinic
ester 15 in 83% yield from 14. An osmium-catalyzed
dihydroxylation[17,18b,c] of the olefin (E)-15, followed by an
oxidative cleavage of the resulting diol using either Pb(OAc)4 or
PhI(OAc)2,[18c] were then performed to afford the B-type
liquidambin-like vescalin precursor 16 in 82% vs 62% yield from
15 (Scheme 3, see details in the Supporting Information).
This precursor 16 resembles liquidambin (6, Scheme 1) in
several structural criteria, including the C-1 aldehyde function,
the 5-O-galloyl group and the 2,3-O-(S)-HHDP unit, which are
both adequately protected in anticipation of the C-glucosidation
step (i.e., with fluoride-labile silyl groups in meta-positions) and
the NHTP-forming terarylation step (i.e., with benzyl groups in
para-positions as per Yamada’s method). Moreover, the cyclic
benzylidene protecting group is a useful surrogate of the 4,6-O-
HHDP unit of liquidambin, which should contribute to maintain
the open-chain glucose core and the 2,3-O-HHDP unit of 16 in
an appropriate conformational status for facilitating the
intramolecular C-arylglucosidation reaction. This crucial role
played by this cyclic protecting group was previously evidenced
in the context of the synthesis of 9.[10b] Hence, we had surmised
that the desired C-arylglucosidation could here be achieved
during the desilylation of 16, as long as anhydrous yet acidic
conditions could be imposed to the reaction medium. Such
conditions should prevent any adventitious hydrolytic release of
the 4,6-O-benzylidene group, while possibly offering a proton-
mediated electrophilic assistance for the nucleophilic addition to
the C-1 aldehyde function. This was successfully accomplished
by treating 16 with TBAF (10 equiv) in the presence of acetic
acid (30 equiv) and molecular sieves in anhydrous THF
(Scheme 4, see Table S3 in the Supporting Information). The
resulting A-type benzylic alcohol 17 was thus generated as a 1:2
α/β epimeric mixture, which was separated by column
chromatography to furnish α-17 and β-17 in 25% and 56% yields,
respectively. With the major epimer β-17 in hands, we were thus
ready to take on the focal and last C–C bond-forming step
toward (–)-1, as per the Wynberg–Feringa–Yamada oxidative
coupling approach (Table 1).[15,16] Initial attempts under standard
Yamada’s conditions in MeOH[16e] led to an undesired n-
butylamino-containing oxidized derivative 18 (not shown, see the
Supporting Information), the yield of which increased from ca
15% to 49% upon changing the solvent to MeCN (Entries 1 & 2).
The use of the bidentate tetramethylethylenediamine (TMEDA)
in MeOH provoked full degradation of the material (Entry 3).
After trying several other amines without any success, we ended
up using the natural tetracyclic diamine (–)-sparteine, well-
known for its copper(II)-chelating properties[19a,b] and previously
used for coupling naphthols into binaphthyls,[19c,d] and we were
gratified by the observation of the atroposelective formation of
the desired product β-19 (Scheme 4) in 17% yield (Entry 4).
Increasing the amount of CuCl2 to 5 equivalents and of (–)-
sparteine to 20 equivalents accelerated the reaction and
increased the yield of β-19 to 27% (Entry 5). This compound was
the only isolatable NHTP-bearing product.
OTBS
OBn
Ph
5
O
O
O
6
3
OTBS
2
O
4
O
Ph
1
3
OH
OH
5
O
O
O
O
TBSO
O
O
2
1
TBAF (10 equiv), AcOH (30 equiv)
THF, 4 Å MS,
O
O
O
O
BnO
O
O
rt for 21 h, then reflux for 4 h
HO
S
S
16
TBSO
OBn
OH
OH
OH
HO
TBSO
OTBS
BnO
NHTP-forming
atroposelective
oxidative coupling
OBn
OBn
α-17 25%
β-17 56%
separated by column
chromatography
Ph
O
see Table 1
O
O
OH
O
N
N
O
O
O
S
OH
1. H2, Pd(OH)2, THF
2. 0.1 N aq. HCl
HO
(–)-sparteine
O
R
(–)-1 41%
BnO
CD
OBn
OH
HO
OH
OH
β-19
41%
40$
30$
20$
10$
0$
synthetic vescalin
natural vescalin
N
N
Me
Me
OBn
N,N'-dimethylbispidine
(bispidine)
!10$
!20$
λ [nm]
200$
250$
300$
350$
Scheme 4. Conversion of the liquidambin-like precursor 16 into vescalin (1).
Table 1. NHTP-forming atroposelective oxidative coupling.
CuCl2
equiv
Amine
(equiv)
Conditions:[a]
rt, solvent, time
18
%
Entry
β-19
%
[b]
[b]
n-BuNH2
(30)
MeOH,
30 min
1
2
3
4
5
6
2
15
0
n-BuNH2
(30)
MeCN,
30 min
2
49
0
0
TMEDA
(10)
MeOH,
60 min
2.5
2.5
5
0
(–)-sparteine
(10)
MeOH,
60 min
0
17
27
41
(–)-sparteine
(20)
MeOH,
10 min
0
bispidine
(20)
MeOH,
15 min
5
0
[a] 10 mg scale, [β-17] = 5-10 mM. [b] isolated yields.
Although these results were encouraging, we were nevertheless
convinced that the use of such a chiral alkaloid has no influence
on the atroposelectivity of the reaction, which is essentially
induced by the asymmetry of the glucosidic substrate. However,
we surmised that the 3,7-diazabicyclo[3.3.1]nonane scaffold of
sparteine must play an advantageous role as a copper(II)-
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10.1002/anie.201707613
Angewandte Chemie International Edition
COMMUNICATION
chelating inductor[19] of the intramolecular C–C bond formation.
Thus, we performed this oxidative phenolic coupling reaction
using the simpler and achiral sparteine analogue N,N’-
dimethylbispidine,[20] which also rapidly led to the formation of β-
19, isolated in 41% yield (Entry 6), together with ca 17% of
recovered starting β-17. Longer reaction times caused
degradation of these materials, likely through methanolysis and
overoxidation. The capacity of both this bispidine and (–)-
sparteine to induce the intramolecular coupling of the
digalloylated glucopyranoside 12 into 13 (Scheme 3) was then
also verified. In this case, (–)-sparteine turned out to be more
efficient than both the bispidine and n-butylamine, affording the
biaryl 13 in a significantly increased yield of 68% (Scheme 3).
Finally, a hydrogenolytic debenzylation of β-19, followed by a
hydrolytic release of the 4,6-O-benzylidene group (Scheme 4),
gave rise to (–)-vescalin (1) in 41% yield, after purification by
preparative reverse-phase HPLC, which inevitably occasions
some loss of such a polyphenolic material. All characterization
criteria, including circular dichroism data, are in agreement with
those of natural vescalin,[3,4] hence attesting that the penultimate
copper(II)/bispidine-mediated coupling step of this synthesis
forged its NHTP unit with the correct atropisomerism.
[5]
[6]
a) T. Hatano, R. Kira, M. Yoshizaki, T. Okuda, Phytochemistry 1986, 25,
2787-2789; b) T. Okuda, T. Hatano, T. Kaneda, M. Yoshizaki, T.
Shingu, Phytochemistry 1987, 26, 2053-2055.
a) T. Tanaka, S. Kirihara, G.-i. Nonaka, I. Nishioka, Chem. Pharm. Bull.
1993, 41, 1708-1716; b) S. Quideau, M. Jourdes, D. Lefeuvre, P.
Pardon, C. Saucier, P.-L. Teissedre, Y. Glories in Recent Advances in
Polyphenol Research, Vol. 2 (Eds.: C. Santos-Buelga, M. T. Escribano-
Bailon, V. Lattanzio), Wiley-Blackwell, Oxford, 2010, pp. 81-137; c) M.
Jourdes, D. Lefeuvre, S. Quideau in Chemistry and Biology of
Ellagitannins
–
An Underestimated Class of Bioactive Plant
Polyphenols (Ed.: S. Quideau), World Scientific Publishing/Imperial
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In summary, we have accomplished the first total synthesis
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Acknowledgements
Financial support from the Ministère de la Recherche, including
a doctoral assistantship for A.R., and from the CNRS is
gratefully acknowledged. The authors also wish to thank
Nicoletta Brindani and Luana Pulvirenti from the Universities of
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Keywords: ellagitannins • natural products • oxidative coupling •
plant polyphenols • total synthesis
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The total synthesis of a first member
of the nonahydroxytriphenoylated
(NHTP) C-glucosidic ellagitannins, (–)-
vescalin, is described via a route
closely tailored to the commonly
proposed sequence of events leading
to its biogenesis. Its characteristic
2,3,5-(S,R)-NHTP unit was elaborated
thanks to a copper(II)-mediated
Wynberg–Feringa–Yamada-type
phenolic coupling using the achiral
bicyclic diamine N,N’-
Antoine Richieu, Philippe A. Peixoto,
Laurent Pouységu, Denis Deffieux,* and
Stéphane Quideau*
Page No. – Page No.
Bio-inspired Total Synthesis of (–)-
Vescalin, A Nonahydroxy-
triphenoylated C-Glucosidic
Ellagitannin
dimethylbispidine.
This article is protected by copyright. All rights reserved.