First total synthesis of the natural product 1,3-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucopyranoside

Article abstract of DOI:10.1016/S0040-4020(01)01210-8

A straightforward synthesis of the natural product 1,3-di-O-galloyl-4,6-O-(S)-hexahydroxy-diphenoyl-β-D-glucopyranoside (7) was achieved based on a regio- and stereoselective galloylation of the 1,3-diol derivative of D-glucopyranose 2 to the β-D-glucopyranoside 3. Subsequent acylation of monoester 3 to the diester 4 followed by the removal of the benzylidene protecting group led to the formation of the corresponding 4,6-diol derivative of D-glucopyranoside 5. A further double esterification of the (rac)-hexabenzyloxydiphenic acid with the appropriately substituted 4,6-diol derivative of D-glucopyranoside 5 allowed us to assemble the carbon framework of the target 7. Hydrogenolysis of the tetraester 6 as the precursor of the target compound over palladium on charcoal gave the natural product 7.

Full text of DOI:10.1016/S0040-4020(01)01210-8

TETRAHEDRON
Pergamon
Tetrahedron 58 +2002) 1159±1163
First total synthesis of the natural product 1,3-di-O-galloyl-4,6-O-
ꢀS)-hexahydroxydiphenoyl-b-d-glucopyranoside
Karamali Khanbabaeep and Mathias Groûer
È
Fachbereich Chemie und Chemietechnik der Universitat Paderborn, Warburger Straûe 100, 33098 Paderborn, Germany
Received 17 September 2001; revised 26 November 2001; accepted 5 December 2001
AbstractÐA straightforward synthesis of the natural product 1,3-di-O-galloyl-4,6-O-+S)-hexahydroxy-diphenoyl-b-d-glucopyranoside +7)
was achieved based on a regio- and stereoselective galloylation of the 1,3-diol derivative of d-glucopyranose 2 to the b-d-glucopyranoside 3.
Subsequent acylation of monoester 3 to the diester 4 followed by the removal of the benzylidene protecting group led to the formation of
the corresponding 4,6-diol derivative of d-glucopyranoside 5. A further double esteri®cation of the +rac)-hexabenzyloxydiphenic acid with
the appropriately substituted 4,6-diol derivative of d-glucopyranoside 5 allowed us to assemble the carbon framework of the target 7.
Hydrogenolysis of the tetraester 6 as the precursor of the target compound over palladium on charcoal gave the natural product 7. q 2002
Elsevier Science Ltd. All rights reserved.
1. Introduction
that had other functional groups +hexahydroxydiphenoyl,
valoneoyl, dehydrodigalloyl, isodehydrodigalloyl, lacto-
nized valoneoyl, hellinoyl, euphorbinoyl, dehydroeuphorbi-
noyl or woodfordinoyl group). The methylated derivative,
nonacosa-O-methylcoriariin A, was essentially inactive,
suggesting the requirement of a phenolic hydroxyl group.
Three condensed tannins +2)-epicatechin 3-O-gallate +ECG)-
dimer, ECG-trimer and ECG-tetramer) signi®cantly stimu-
lated both monocyte iodination and their interleukin-1-like
factor production. The results suggest the dependence of
stimulation of monocyte iodination by tannins and related
polyphenols on their molecular weights.5
The natural product 1,3-di-O-galloyl-4,6-O-+S)-hexa-
hydroxydiphenoyl-b-d-glucopyranoside +7) was isolated
by Yoshida et al. from Bredita tuberculatata,1,2 the ¯owers
of Tamarix pakistanica,1 the leaves of Reaumuria hirtella
JAUB and sp. +Tamaricaceae)2 by column chromatography
of the ethyl acetate extract and from the leaves of Acacia
raddiana.3 Although it is mentioned that this compound was
isolated for the ®rst time in 1991,3 the ®rst isolation of this
natural product seems to be from the Nippon Shinyaku Co.,
Ltd, Japan in 1983.2 This compound was also obtained by
partial degradation of the trimeric natural ellagitannin
`hirtellin T1' in hot water.4 Hirtellin T1 itself was isolated
from R. hirtella.4 Sakagami and co-workers investigated the
biological activities of natural product 7 along with some
other tannins and related compounds for their ability to
stimulate monocyte iodination and interleukin-1 produc-
tion5 as well as anti-HIV activity.6 Their anti-HIV activity
was demonstrated to be mediated, at least in part, by inhi-
bition of HIV adsorption to the cells.6 Various tannins and
related compounds were compared for their ability to stimu-
late the iodination +incorporation of radioactive iodine into
an acid-insoluble fraction) of human peripheral blood
monocytes. The stimulating activity of most of the mono-
meric and dimeric hydrolyzable tannins was generally
higher than that of the trimeric and tetrameric compounds.
Compounds that had dehydrohexahydroxydiphenoyl or
chebuloyl groups had considerably less activity than those
In the preceding review7 we reported on the synthesis of the
ellagitannins strictinin, praecoxin B, pterocarinin C,
Mahtabin A and Pariin M, etc., each possessing a +S)- or
+R)-hexahydroxydiphenoyl +HHDP) moiety located at the
2,3 or the 4,6 positions of the d-glucopyranose or d-gluconic
acid. For the synthesis of those ellagitannins having one
additional galloyl residue at the anomeric center of their
d-glucopyranosyl core, we usually used a highly b-stereo-
selective anomeric esteri®cation8 of the corresponding
a,b-anomeric mixture with tri-O-benzylgalloyl chloride9
in the presence of dried triethylamine +Et3N). To examine
not only the b-selectivity but also the regioselectivity of the
galloylation reaction of diol derivatives of d-glucopyranose,
we decided to acylate the diol 2 with the tri-O-benzylgalloyl
chloride under the same reaction conditions as mentioned
earlier. For this purpose, we started with ortho-nitrobenzyl
2-O-benzyl-4,6-O-benzylidene-d-glucopyranoside +1)10 and
removed ®rst the photolytically cleavable o-nitrobenzyl
protecting group at the anomeric center of the latter by
irradiation with UV light at 320 nm in a photochemical
apparatus to obtain the corresponding diol 2. Subsequently,
Keywords: total synthesis; ellagitannin; d-glucopyranoside.
Corresponding author. Fax: 149-525-1603245;
e-mail: kkh@chemie.uni-paderborn.de
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)01210-8

1160
K. Khanbabaee, M. Groûer / Tetrahedron 58 02002) 1159±1163
Scheme 1. Synthesis of diester 4. Reagents and conditions: +a) hn, THF, EtOH, H2O, 8 h; +b) tri-O-benzylgalloyl chloride, dried Et3N, dried CH2Cl2, re¯ux,
4 h; +c) tri-O-benzylgallic acid, DMAP, DCC, dried CH2Cl2, re¯ux, 12 h.
we examined the regio- and stereoselective monogalloyl-
ation reaction at the anomeric center of the diol 2 with
3,4,5-tri-O-benzylgalloyl chloride under b-selective reac-
tion conditions in the presence of Et3N. This reaction led
exclusively to the formation of the desired compound
1-O-+tri-O-benzylgalloyl)-2-O-benzyl-4,6-O-benzylidene-
b-d-glucopyranoside +3) in high yield. The reactivities of
both C1±OH and C3±OH groups of the d-glucopyranose
seem to be very different, so there was no need to protect
®rst the C3±OH group in order to galloylate the anomeric
center of the diol 2. For the synthesis of natural product 7,
we decided to instal one more galloyl group at the C3±OH
of the d-glucopyranosyl core of monoester 3 at this stage,
which could be achieved by further esteri®cation of the
latter with tri-O-benzylgallic acid under Steglich con-
ditions11 in the presence of 4-N,N-dimethylaminopyridine
+DMAP) and dicyclohexylcarbodiimide +DCC) +Scheme 1).
®gured tetraester 6 as the precursor of natural ellagitannin
7 along with a considerable amount of an uncharacterized
polar product, which possesses +R)-HBODPs. To determine
the absolute con®guration of the obtained stereoisomer 6,
the tetraester 6 was subjected to hydrolysis using anhydrous
potassium hydroxide prepared from potassium tert-butoxide
and a trace of water in dried THF as proposed by Gassman
and Schenk.13 An optically pure +S)-HBODA was obtained
from this reaction as shown by comparison of its speci®c
rotation with that reported for +S)-HBODA.12 Thus, the
absolute con®guration of the observed atropisomer 6 was
unambiguously determined to be +S). The debenzylation of
tetraester 6 was achieved by hydrogenolysis over Pd/C to
furnish the natural product 7 as a faintly yellow powder
following reversed phase thin layer chromatographic puri®-
cation +Scheme 2). The identity of the synthetic and natural
ellagitannin 7 was evaluated by the comparison of the
NMR-data of synthetic ellagitannin 7 with those published
for the natural product 1,3-di-O-galloyl-4,6-O-+S)-hexa-
hydroxydiphenoyl-b-d-glucopyranoside.1,3
Toward the convergent synthesis of natural product 7 it was
planed to assemble the carbon framework of the latter by a
diastereoselective intramolecular double esteri®cation of
the +rac)-hexabenzyloxydiphenic acid [+rac)-HBODA]12
with the diol 5. For this purpose, the diester 4 was treated
®rst with diluted HCl to remove the benzylidene protecting
group at the 4,6 positions of the diester 4 to generate the 4,6-
diol derivative of d-glucopyranoside 5. As anticipated, the
esteri®cation of +rac)-HBODA with diol 5 occurred dia-
stereoselectively to furnish the corresponding +S)-con-
2. Experimental
2.1. General
Nuclear magnetic resonance +1H and 13C NMR) spectra
were recorded by use of a Bruker AMX 300 +300 MHz)
Scheme 2. Total synthesis of 7. Reagents and conditions: +a) 2N HCl, 788C, 8 h; +b) +rac)-HBODA, DMAP, DCC, dried CH2Cl2, rt, 24 h; +c) Pd/C±H2, dried
THF, 608C, 48 h.

K. Khanbabaee, M. Groûer / Tetrahedron 58 02002) 1159±1163
1161
and a Bruker ARX 200 +200 MHz) spectrometer. Chemical
shifts are reported in ppm +d) down®eld relative to tetra-
methylsilane as a standard +in CDCl3). The degree of substi-
tution on carbon atoms was determined by DEPT; q, t, d and
s designated primary, secondary, tertiary, and quaternary
carbon atoms, respectively. HBODP stands for hexabenzyl-
oxydiphenoyl moiety, Gall stands for galloyl moiety and
Gluc. stands for d-glucosyl moiety. Melting points were
determined by use of a Gallenkamp melting point apparatus
and they are uncorrected. Infrared +IR) spectra were obtained
by use of a FT-IR spectral photometer Nicolet 510 P +KBr).
Ultraviolet/visible +UV/vis) spectra were recorded by use of
a Shimadzu UV±vis spectral photometer UV-2101 PC; lmax
in nm +log 1). Elemental analyses were perfomed by use of
a Perkin±Elmer Elemental Analyser 2400.
argon for 4 h. The reaction mixture was allowed to cool to
room temperature and the solvent was removed in vacuo.
The residue was separated by column chromatography
+CH2Cl2, Rfˆ0.33) to give the anomeric acylated monoester
3 +2.40 g, 3.08 mmol, 71%) as a white powder, mp 49±
20
558C, [a]D ˆ274.78 +cˆ0.56, CHCl ). IR +CCl ): nˆ
Ä
3
4
3467 cm21, 3090, 3064, 3032, 2929, 2878, 1734, 1584,
1502, 1455, 1429, 1372, 1336, 1197, 1088. UV/vis
+CH2Cl2): lmax +log 1)ˆ259 nm +4.32). 1H NMR +300
MHz, CDCl3): d +ppm)ˆ3.00 +s, 1H, 3-OH), 3.54±3.56
+m, 2H), 3.61 +t, Jˆ8.4 Hz, 1H), 3.69 +t, 1H), 3.92 +t, Jˆ
8.6 Hz, 1H), 4.31 +dd, Jˆ3.29, 10.6 Hz, 1H), 4.63±4.73 +m,
2H), 5.03± 5.12 +m, 4H, OCH2Ph), 5.15 +s, 2H, OCH2Ph),
5.48 +s, 1H, PhCH), 5.90 +d, J1,2ˆ8.0 Hz, 1H, Gluc.-H-1),
7.19±7.48 +m, 27H, Ar-H). 13C NMR +50 MHz, CDCl3): d
+ppm)ˆ67.3 +t), 69.0 +s, Gluc.-C-6), 71.8 +s, OCH2Ph), 74.2
+t), 75.5 +s, OCH2Ph), 75.6 +s, OCH2Ph), 80.8 +t), 81.3 +t),
95.2 +t, Gluc.-C-1), 102.4 +t), 110.1 +t, Gall-C-2 and Gall-C-
6), 124.3 +q, Gall-C-1), 126.9 +t), 127.9 +t), 128.0 +t), 128.5
+t), 128.6 +t), 128.7 +t), 128.9 +t), 129.0 +t), 129.1 +t), 129.8
+t), 137.0 +q), 137.4 +q), 137.8 +q), 138.2 +q), 143.6 +q, Gall-
C-4), 153.1 +q, Gall-C-3 and Gall-C-5), 164.7 +q, COOR).
MS +FAB/NBA): m/z +%)ˆ781 +0.12) [M11H], 781 +0.08)
[M1], 673 +0.1) [M12C7H7O], 583 +0.1), 513 +0.12), 423
+26) [tri-O-benzylgalloyl +C28H23O41)], 331 +4), 304 +2),
271 +1), 255 +1), 241 +8), 197 +6), 181 +12), 107 +6)
[C7H7O1], 105 +5), 92 +14), 91 +100) [C7H71]. Analysis:
C48H44O10 +780.87) calcd C, 73.83; H, 5.68; found C,
73.55; H, 5.86.
2.1.1. 2-O-Benzyl-4,6-O-benzylidene-d-glucopyranose ꢀ2).
A solution of o-nitrobenzyl protected d-glucopyranoside
1 +4.07 g, 8.25 mmol) in tetrahydrofuran +THF) +150 ml),
ethanol +150 ml) and water +0.5 ml) was irradiated under
argon for 8 h in a photochemical apparatus +PYREX) at
320 nm. The solvent was removed in vacuo to give a yellow
oil. Column chromatography on silica gel [+CH2Cl2/AcOEt,
7:3; Rfˆ0.23] gave diol 2 +56%) as a faintly yellow powder
as an a,b-anomeric mixture +a/b ratio in acetone-d6 6:7, mp
21
1828C +lit.14 180±1818C, lit.15,16 1758C), [a]D ˆ211.28
+cˆ0.53, CHCl3), lit.14 [a]Dˆ268 +cˆ0.5, CHCl3), lit.15
24
[a]D ˆ168 +cˆ1.0, Py). IR +KBr): nˆ3434 cm21, 3092,
Ä
3065, 3032, 2972, 2934, 2874, 1498, 1450, 1384, 1216,
1167, 1085, 1031. UV/vis +MeOH): lmax +log 1)ˆ242 nm
1
+4.32). H NMR +300 MHz, acetone-d6): d +ppm)ˆ3.28 +t,
2.1.3. 1,3-Di-O-ꢀtri-O-benzylgalloyl)-2-O-benzyl-4,6-O-
benzylidene-b-d-glucopyranoside ꢀ4). A solution of
monoester 3 +1.12 g, 1.44 mmol), tri-O-benzylgallic acid
+0.95 g, 2.16 mmol, 1.5 equiv.), DCC +0.45 g, 2.16 mmol,
1.5 equiv.) and DMAP +0.26 g, 2.16 mmol, 1.5 equiv.) in
dry CH2Cl2 +50 ml) was re¯uxed under argon for 12 h.
The reaction mixture was allowed to cool to room tempera-
ture, and the white solid +dicyclohexylurea) was ®ltered off.
The solvent was removed in vacuo to give a yellow viscous
oil. Column chromatography of the crude product on silica
gel +CH2Cl2, Rfˆ0.56) gave diester 4 +1.54 g, 1.28 mmol,
Jˆ8.2 Hz, 1H, Gluc.-H-2b), 3.39±3.54 +m, 4H, Gluc.-H-
2a, Gluc.-H-4a/b Gluc.-H-5b), 3.67±3.84 +m, 3H, Gluc.-
H-3b, OCH2Ph), 3.96±4.04 +ddd, Jˆ14.8, 10.0, 4.8 Hz, 1H,
Gluc.-H-5a), 4.08±4.18 +m, 2H, Gluc.-C-3a, Gluc.-H-6a),
4.23 +dd, J6b,5bˆ4.8 Hz, Jgemˆ10.3 Hz, 1H, Gluc.-H-6b),
4.63 +d, Jˆ3.7 Hz, 1H, 3-OHa), 4.73 +d, Jˆ4.0 Hz, 1H,
3-OHb), 4.79±4.87 +m, 3H, Gluc.-H-1b, CH2Ph), 4.99 +d,
Jgemˆ11.5 Hz, 1H, OCH2Ph), 5.34 +t, J1a,2aˆ3.8 Hz, 1H,
Gluc.-H-1a), 5.60 +s, 1H, H-7), 5.63 +d, JOHa,1aˆ4.3 Hz,
1H, OH), 6.21 +d, JOHb,1bˆ6.4 Hz, 1H, 1-OHb), 7.26±7.52
+m, 10H, Ar-H). 13C NMR +50 MHz, acetone-d6): d +ppm)ˆ
62.6 +t, Gluc.-C-5a), 66.5 +t, Gluc.-C-5b), 68.9 +s, Gluc.-C-
6b), 69.3 +s, Gluc.-C-6a), 70.4 +t, Gluc.-C-3a), 72.7 +s,
OCH2Pha), 73.8 +t, Gluc.-C-3b), 74.7 +s, OCH2Phb), 81.0
+t, Gluc.-C-2a), 81.8 +t, Gluc.-C-4b), 82.5 +t, Gluc.-C-4a),
84.7 +t, Gluc.-C-2b), 92.1 +t, Gluc.-C-1a), 98.3 +t, Gluc.-C-
1b), 101.7 +t, C-7b), 101.8 +t, C-7a), 126.8 +t), 126.9 +t),
127.5 +t), 127.7 +t), 128.0 +t), 128.1 +t), 128.3 +t), 128.4 +t),
128.5 +t), 129.1 +t), 138.7 +q), 138.8 +q), 139.6 +q), 139.9 +q).
MS +FAB/glycerin): m/z +%)ˆ359 +9) [M11H], 341 +5)
[+M11H)2H2O], 187 +10), 185 +27), 165 +10), 149 +18),
147 +12), 145 +10), 131 +14), 129 +32), 119 +10), 117 +16),
115 +9), 107 +15) [C7H7O1], 105 +11) [C7H5O1], 103 +22),
93 +88), 92 +11), 91 +100) [C7H71], 75 +62), 73 +16), 61 +8).
Analysis: C20H22O6 +358.39) calcd C, 67.03; H, 6.19; found
C, 67.06; H, 6.12.
21
89%) as a white powder, mp 151±1538C, [a]D ˆ231.38
+cˆ1.01, CH Cl ). IR +KBr): nˆ3069 cm21, 3027, 2924,
Ä
2878, 1734, 1714, 1584, 1497, 1460, 1429, 1378, 1336,
2
2
1197, 1093. UV/vis +CH2Cl2): lmax +log 1)ˆ248 nm
1
+3.97). H NMR +200 MHz, CDCl3): d +ppm)ˆ3.92±4.01
+m, 5H), 4.08 +t, Jˆ8.3 Hz, 1H), 4.56 +d, Jˆ5.5 Hz, 1H,
Gluc.-H-6), 4.69 +d, Jgemˆ11.8 Hz, 1H, OCH2Ph), 4.79 +d,
Jgemˆ11.8 Hz, 1H, OCH2Ph), 5.12 +t, 1H, Gluc.-H-6), 5.25±
5.32 +m, 14H, OCH2Ph), 5.65 +s, 1H, PhCH), 5.88 +t, Jˆ
8.7 Hz, 1H, Gluc.-H-3), 6.27 +d, J1,2ˆ7.8 Hz, 1H, Gluc.-H-
1), 7.14±7.24 +m, 4H, Gall-H-2 and Gall-H-6 or Gall-H-20
and Gall-H-60), 7.39±7.62 +m, 40H, Ar-H). 13C NMR
+50 MHz, CDCl3): d +ppm)ˆ67.4 +t), 69.1 +s, Gluc.-C-6),
71.88 +s, OCH2Ph), 71.93 +s, OCH2Ph), 74.2 +t), 75.0 +s,
OCH2Ph), 75.7 +s, OCH2Ph), 79.1 +t), 79.2 +t), 95.6 +t,
Gluc.-C-1), 102.0 +t, C-7), 110.2 and 110.3 +t, Gall-C-2
and Gall-C-6 or Gall-C-20 and Gall-C-60), 124.4 +q), 125.3
+q), 126.8 +t), 128.0 +t), 128.1 +t), 128.4 +t), 128.6 +t), 128.7
+t), 128.8 +t), 128.83 +t), 129.1 +t), 129.2 +t), 129.6 +t), 137.0
+q), 137.2 +q), 137.3 +q), 137.6 +q), 137.8 +q), 137.9 +q),
143.3 +q), 143.9 +q), 153.1 +q), 153.3 +q), 164.5 +q, COOR),
165.4 +q, COOR). MS +ESI/acetone): m/z +%)ˆ1225.5 +100)
2.1.2. 1-O-ꢀTri-O-benzylgalloyl)-2-O-benzyl-4,6-O-benzyl-
idene-b-d-glucopyranoside ꢀ3). A solution of diol 2
+1.55 g, 4.32 mmol), tri-O-benzylgalloyl chloride +2.38 g,
5.19 mmol, 1.2 equiv.), a catalytic amount of dry triethyl-
amine +6 drops) and dry CH2Cl2 +50 ml) was re¯uxed under

1162
K. Khanbabaee, M. Groûer / Tetrahedron 58 02002) 1159±1163
[+M1Na)1], 1083.4 +25), 997.9 +23), 953.9 +28), 909.9 +34),
865.9 +25), 821.9 +15), 733.7 +11), 306.4 +9). Analysis:
C76H66O14 +1280.35) calcd C, 75.86; H, 5.53; found C,
74.96; H 5.51.
+s, OCH2Ph), 76.0 +s, OCH2Ph), 79.0 +t), 95.3 +t, Gluc.-C-1),
108.1 +t), 108.5 +t), 110.1 +t), 110.2 +t), 124.1 +q), 124.2 +q),
124.4 +q), 125.1 +q), 128.0 +t), 128.2 +t), 128.5 +t), 128.6 +t),
128.7 +t), 128.7 +t), 128.8 +t), 128.9 +t), 129.0 +t), 129.1 +t),
129.1 +q), 129.2 +t), 129.4 +q), 130.3 +q), 136.9 +q), 137.1
+q), 137.5 +q), 137.9 +q), 138.0 +q), 138.1 +q), 138.2 +q),
138.3 +q), 140.3 +q), 143.5 +q), 143.9 +q), 144.9 +q), 145.3
+q), 152.8 +q), 153.0 +q), 153.1 +q), 153.2 +q), 153.3 +q),
164.6 +q, COOR), 166.1 +q, COOR), 167.8 +q, COOR),
168.0 +q, COOR). MS +ESI/acetone): m/z +%)ˆ1762.4,
1616, 1100.9. Analysis: C125H104O22 +1958.19) calcd C,
76.67; H, 5.35; found C, 76.66; H, 5.42.
2.1.4.
1,3-Di-O-ꢀtri-O-benzylgalloyl)-2-O-benzyl-b-d-
glucopyranoside ꢀ5). To a stirred solution of diester 4
+1.34 g, 1.12 mmol) in THF +30 ml) 2N HCl +30 ml) was
added slowly at 608C. The mixture was stirred at 788C for
8 h. After cooling to room temperature the reaction mixture
was quenched with saturated NaHCO3, extracted 6 times
with CH2Cl2 +50 ml). Drying of the combined organic
extracts +Na2SO4) and evaporation under reduced pressure
gave an oily residue +CH2Cl2/Et2O 10:1, Rfˆ0.21). The
crystallization of the oily residue +CH2Cl2/n-hexane)
afforded the diol 5 +1.10 g, 0.98 mmol, 88%) as white
2.1.6. 1,3-Di-O-galloyl-4,6-O-ꢀS)-hexahydroxydiphenoyl-
b-d-glucopyranoside ꢀ7). A suspension of tetraester 6
+160 mg), Pd/C +100 mg, 10%) and dry THF +45 ml) was
®rst degased with argon +3 times) to remove O2, and hydro-
gen +H2) was conducted slowly through the reaction mixture
at 608C for 48 h. The reaction mixture was allowed to
cool to room temperature, the solid was ®ltered off through
celite, and the celite was washed with a mixture of acetone/
methanol +80:20, 60 ml). The solvent was removed under
reduced pressure to give an oily residue, which contains
the polyphenolic compound 7 along with some partially
debenzylated products. The puri®cation of the ellagitannin
7 was carried out by reversed phased chromatography +H2O/
MeOH, 10:2) to afford natural product 7 +45 mg, 70%) as a
21
powder, mp 1728C, [a]D ˆ121.68 +cˆ1.07, CH2Cl2). IR
+KBr): nˆ3390 cm21, 3271, 3069, 3022, 2924, 2862, 1740,
Ä
1724, 1590, 1502, 1455, 1424, 1383, 1336, 1202, 1119,
1
1072. UV/vis +CH2Cl2): lmax +log 1)ˆ282 nm +3.89). H
NMR +200 MHz, CDCl3): d +ppm)ˆ3.73±3.78 +m, 1H),
3.85±4.02 +m, 5H), 4.58 +d, Jgemˆ11.7 Hz, 1H, OCH2Ph),
4.70 +d, Jgemˆ11.7 Hz, 1H, OCH2Ph), 5.15±5.22 +m, 16H,
OCH2Ph), 5.49 +t, Jˆ9.0 Hz, 1H), 6.11 +d, J1,2ˆ7.9 Hz, 1H,
Gluc.-H-1), 7.09 +s, 4H, Ar-H), 7.34±7.49 +m, 35H, Ar-H).
13C NMR +50 MHz, CDCl3): d +ppm)ˆ62.3 +s, Gluc.-C-6),
69.9 +t), 71.7 +s, OCH2Ph), 71.8 +s, OCH2Ph), 74.9 +s,
OCH2Ph), 75.6 +s, OCH2Ph), 76.7 +t), 78.4 +t), 78.7 +t),
95.1 +t, Gluc.-C-1), 109.9 or 110.1 +t, Gall-C-2 and Gall-
C-6 or Gall-C-20 and Gall-C-60), 124.4 or 124.8 +q, Gall-C-1
or Gall-C-10), 127.9 +t), 128.0 +t), 128.3 +t), 128.4 +t), 128.5
+t), 128.6 +t), 128.69 +t), 128.7 +t), 129.0 +t), 136.9 +q), 137.0
+q), 137.6 +q), 137.7 +q), 137.75 +q), 143.3 +q), 143.7 +q),
153.0 +q), 153.1 +q), 164.7 +q, COOR), 167.1 +q, COOR).
MS +ESI/acetone): 1137.5 +67) [+M1Na)1], 953.9 +94),
909.8 +100), 625.6 +39), 517.5 +29), 360.5 +29), 306.3 +18),
242.3 +23), 158.1 +82), 100.1 +54). Analysis: C69H62O14
+1115.24) calcd C, 74.31; H, 5.60; found C, 74.04; H, 5.68.
22
brownish powder, decomp. 1788C, [a]D ˆ116.28 +cˆ1.0,
27
MeOH), lit.1 [a]Dˆ1248 +cˆ1.0, MeOH), lit.3 [a]D
ˆ
2608 +cˆ0.61, MeOH). IR +KBr): nˆ3340 cm21, 3005,
Ä
2956, 2924, 2873, 2852, 1701, 1616, 1448, 1354, 1319,
1205, 1036. UV +MeOH): lmax +log 1)ˆ 303 nm +4.33),
1
lit.3 lmax +MeOH)ˆ275 nm. H NMR +300 MHz, acetone-
d6/D2O): d +ppm)ˆ3.82 +d, Jgemˆ13.2 Hz, 1H, Gluc.-H-6),
3.99 +dd, Jˆ8.2, 9.2 Hz, 1H, Gluc.-H-2), 4.35 +dd, Jˆ5.9,
9.9 Hz, 1H, Gluc.-H-5), 5.06 +t, Jˆ9.9 Hz, 1H, Gluc.-H-4),
5.30 +dd, J6,5ˆ6.5 Hz, Jgemˆ13.4 Hz, 1H, Gluc.-H-6), 5.48
+t, Jˆ9.6 Hz, 1H, Gluc.-H-3), 5.90 +d, J1,2ˆ8.2 Hz, 1H,
Gluc.-H-1), 6.47 and 6.62 +s, 2H, HHDP-H-5 or HHDP-
H-50), 7.04 +s, 2H, Gall-H-2 or Gall-H-6), 7.21 +s, 2H,
Gall-H-2 or Gall-H-6). 13C NMR +50 MHz, acetone-d6/
D2O): d +ppm)ˆ62.8 +s, Gluc.-C-6), 70.3 +t, Gluc.-C-4),
71.9 +t, Gluc.-C-2), 72.4 +t, Gluc.-C-5), 75.2 +t, Gluc.-C-
3), 95.4 +t, Gluc.-C-1), 107.4 and 107.5 +t, HHDP-C-5 and
HHDP-C-50), 109.7 and 109.8 +t, Gall-C-2 and Gall-C-6),
115.4 +q), 115.5 +q), 119.9 +q), 120.7 +q), 125.5 +q), 126.0 +q),
136.0 +q), 136.1 +q), 138.5 +q), 139.2 +q), 144.1 +q), 144.7 +q),
144.75 +q), 145.4 +q), 145.7 +q), 165.1 +q, COOR), 166.5 +q,
COOR), 167.5 +q, COOR), 167.9 +q, COOR).
2.1.5. 1,3-Di-O-ꢀtri-O-benzylgalloyl)-2-O-benzyl-4,6-O-
ꢀS)-hexabenzyloxydiphenoyl-b-d-glucopyranoside ꢀ6).
A mixture of diol 5 +1.08 g, 0.96 mmol), racemic hexa-
benzyloxydiphenic acid +0.84 g, 0.96 mmol), DCC +0.51
g, 2.46 mmol, 2.6 equiv.), and DMAP +0.3 g, 2.49 mmol,
2.6 equiv.) in dry CH2Cl2 +20 ml) was stirred under argon
at room temperature for 24 h, and the white solid +dicyclo-
hexylurea) was ®ltered off. The solvent was removed in
vacuo to give a viscous oil. Column chromatography of
the crude product on silica gel +CH2Cl2, Rfˆ0.53) gave
tetraester 6 +0.75 g, 0.38 mmol, 39.5%) as a white powder,
22
mp 58±658C, [a]D ˆ215.08 +cˆ1.15, CH2Cl2). IR +CCl4):
nˆ3091 cm21, 3069, 3033, 2929, 2872, 1750, 1590, 1558,
Acknowledgements
Ä
1502, 1460, 1424, 1372, 1336, 1197, 1098, 1005. UV/vis
+CH2Cl2): lmax +log 1)ˆ285 nm +4.03). 1H NMR +300 MHz,
CDCl3): d +ppm)ˆ3.94 +t, Jˆ8.1 Hz, 1H), 4.04 +d, Jˆ
We thank the Deutsche Forschungsgemeinschaft +Total-
È
synthese), the Universitat Paderborn and the Fonds der
Chemischen Industrie for ®nancial support and Professor
Karsten Krohn for his helpful assistance.
13.2 Hz, 1H), 4.27 +dd, Jˆ5.8, 9.8 Hz, 1H), 4.51 +d, Jgem
ˆ
11.8 Hz, 1H, OCH2Ph), 4.59 +d, Jgemˆ11.6 Hz, 1H,
OCH2Ph), 4.75 +d, Jgemˆ11.0 Hz, 1H, OCH2Ph), 4.82±
5.21 +m, 23H, OCH2Ph), 5.29±5.39 +m, 2H), 5.68 +t, 1H),
6.07 +d, J1,2ˆ7.7 Hz, 1H, Gluc.-H-1), 6.85±7.51 +m, 71H,
Ar-H). 13C NMR +50 MHz, CDCl3): d +ppm)ˆ63.8 +s,
Gluc.-C-6), 70.9 +t), 71.7 +s, OCH2Ph), 71.9 +s, OCH2Ph),
72.7 +t), 74.9 +t), 75.4 +s, OCH2Ph), 75.7 +s, OCH2Ph), 75.7
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