Regioselective acetyl transfer from the aglycon to the sugar in C-glycosylic compounds facilitated by silica gel

Article abstract of DOI:10.1016/S0008-6215(99)00140-8

2'-O-Acetyl C-glycosylic compounds (C-glycosides) were prepared via regioselective acetyl transfer from aglycons to sugar moieties with silica gel in the presence of unprotected primary and secondary hydroxyl groups. Copyright (C) 1999 Elsevier Science Lt

Full text of DOI:10.1016/S0008-6215(99)00140-8

www.elsevier.nl/locate/carres
Carbohydrate Research 320 (1999) 129–137
Note
Regioselective acetyl transfer from the aglycon to the
sugar in C-glycosylic compounds facilitated by silica gel
Toshihiro Kumazawa *, Yasuyuki Akutsu, Shigeru Matsuba, Shingo Sato,
Jun-ichi Onodera
Department of Materials Science and Engineering, Faculty of Engineering, Yamagata Uni6ersity, 4-3-16 Jonan,
Yonezawa, Yamagata 992-8510, Japan
Received 31 March 1999; accepted 3 June 1999
Abstract
2%-O-Acetyl C-glycosylic compounds (C-glycosides) were prepared via regioselective acetyl transfer from aglycons
to sugar moieties with silica gel in the presence of unprotected primary and secondary hydroxyl groups. © 1999
Elsevier Science Ltd. All rights reserved.
Keywords: C-glycosylic compounds; C-glycoside; 2%-O-Acetyl C-glycoside; Regioselective acetyl transfer; Silica gel
While acyltransferases specific for O-glyco-
syl flavonoids have been reported [6], there
appear to be no reports related to acyltrans-
ferases that act on C-glycosyl flavonoids. For
most of the acyl C-glycosyl flavonoids exam-
ined thus far, the acyl groups are linked to the
2%-hydroxyl groups of the glycosyl moieties.
More recently, the regioselective acylation
of the 2%-hydroxyl group of the glucopyra-
nosyl moiety of aloesin using Ichihara’s
method [7] has been reported. This approach
involves the use of various carboxylic acids in
the presence of 1,3-dicyclohexylcarbodiimide
In recent years, the synthesis of aryl C-gly-
cosylic compounds (C-glycosides) [1] and their
bioactivities [2] have become major subjects in
the field of carbohydrates. Among these are
O-acetylated glycosyl moieties [3], for exam-
ple, 2%%-O-acetyl isoorientin, a favonoid com-
pound. Recently, an acyl C-glucosyl chro-
mane was shown to contain topical anti-
inflammatory activity [4], and isoaloeresin D
and aloeresin E inhibit tyrosine oxidation [5].
It is generally thought that the role of acyl
groups on C-glycosyl flavonoids is to increase
their solubility in water, to protect the
molecules from the action of glycosyltrans-
ferases, and to conformationally stabilize their
structures.
(DCC)
and
4-dimethylaminopyridine
(DMAP), which results in an intramolecular
acyl transfer from the aglycon to the glucopy-
ranosyl moiety [8]. In this paper, we wish to
describe the convenient regioselective acetyl-
ation of the 2%-hydroxyl group of C-glycosides
via acetyl transfer from the aglycon to the
sugar moiety with silica gel in the presence of
unprotected primary and secondary hydroxyl
* Corresponding author. Tel.: +81-238-26-3122; fax: +
81-238-26-3413.
E-mail address: tk111@dip.yz.yamagata-u.ac.jp (T. Ku-
mazawa)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00140-8

130
T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
Scheme 1.
mannopyranosyl fluoride [10], or a mixture of
1-O-acetyl-3,4,6-tri-O-benzyl-2-deoxy- -ara-
groups. Investigations of the positions of
acetyl groups on the aglycon moieties before
transfer, as well as the role of the unprotected
sugar in the C-glycoside, were carried out.
We initially observed that a developed TLC
of hydrogenolyzed 4a showed a corresponding
product that was acetylated on the 3-phenolic
hydroxyl group, along with a small amount of
the unexpected 2%-O-acetylated product, when
the plate was dried with a stream of cold air
prior to development. When a stream of hot
air was employed, TLC monitoring showed an
increased yield of 2%-O-acetylated product
without the formation of other byproducts. It
was considered that the C-glycoside having an
acetylated phenolic hydroxyl group positioned
ortho to the 2%-unprotected glycosyl moiety
was efficiently converted to the 2%-O-acetylated
C-glycoside by treatment with silica gel as a
consequence of acetyl transfer.
D
bino-hexopyranose (a/b ratio=92/8) [11] to
give the corresponding C-glycosides, 3a 96%
[9], 3b 28%, 3c 63% and 3d in 56% yield,
respectively. The TBDPS protecting group of
3c was removed by alkaline hydrolysis to give
3c% in 89% yield. Thus, 3a, 3b, 3c% and 3d were
acetylated at the phenolic hydroxyl group of
the aglycon with acetic anhydride, pyridine,
and a catalytic amount of DMAP to afford
4a, 4b, 4c and 4d, respectively (Scheme 1).
These acetylated products were each hy-
drogenolyzed with 10% PdꢀC as a catalyst
under an H2 atmosphere in AcOEt–EtOH. To
our surprise, 4b had already been converted to
the 2%-O-acetylated product 5b in 97% yield in
two steps via regioselective acetyl transfer.
Compounds 4a, 4c, and 4d were hy-
drogenolyzed, and the products were then
refluxed with silica gel (Wakogel C-300®) in
EtOH. For each regioisomer the phenolic hy-
droxyl group of aglycons, 4a and 4c were
converted regioselectively to the same 2%-O-
acetylated product 5a in 98% yield in two
steps with no other byproducts being observed
(Scheme 2). The required reaction time for the
acetyl transfer for 5a (0.5 h) is shorter than
that for 5c, 1 h. This could be due to the fact
that 5a contains an acetylated phenolic hy-
droxyl group at an ortho position to an elec-
tron-withdrawing acetyl group, which is
According to previously described methods1
[9], 2,4-O-benzyl-protected or 2-O-benzyl-4-
O-tert-butyldiphenylsilyl (TBDPS)-protected
phloroacetophenone derivatives reacted with
either 2,3,4,6-tetra-O-benzyl-a-
D
-glucopyra-
nosyl fluoride [10], 2,3,4,6-tetra-O-benzyl-a-
D-
1 The statement that the mixture of C-glucosides afforded
via intermolecular O“C glucoside rearrangement is incor-
rect. The C-glucoside should be a single regioisomer that is
linked to the ortho position of the phenolic hydroxyl group of
the aromatic ring. This fact was determined by 1H NMR
spectra at over 100 °C temperature.

T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
131
Scheme 2.
linked to the aromatic ring. The position of
the acetyl groups of 5a and 5b was determined
by analysis of individual 1H NMR and 1H–1H
COSY spectra. In the 2%-O-acetylated products
5a and 5b, the 1H NMR signals of the individ-
ual H-2% were shifted downfield at 5.33 and
5.21 ppm, respectively, compared with those
of the corresponding unprotected compounds,
6a [12] and 6b. The acetyl group of 5d was not
transferred to any other position on the 2-de-
tored by thin-layer chromatography (TLC),
which was carried out on 0.25 mm Silica Gel
60 F254 plates (E. Merck) using either UV light
for visualization or a 5% ethanolic solution of
ferric chloride or a 5% ethanolic solution of
phosphomolybdic acid with heat as develop-
ing agents. Wakogel C-300® (particle size
0.045–0.075 mm) or Wako Polyamide C-200®
(particle size 0.075–0.15 mm) was used for
column chromatography. Melting points are
uncorrected. Optical rotations were recorded
using CHCl3 or EtOH as solvents on a Jasco
DIP-370 digital polarimeter. IR spectra were
recorded on a Horiba FT-200 IR spectrometer
as KBr pellets. Mass spectra were recorded on
a Jeol JMS-AX-505-HA mass spectrometer
under fast-atom bombardment (FAB) condi-
tions using 3-nitrobenzyl alcohol as the ma-
oxy- -arabino-hexopyranosyl moiety.
D
These results clearly show that the regiose-
lective chemical acetyl transfer from both the
ortho-positioned phenolic hydroxyl groups of
the aglycon to the sugar moiety in the C-gly-
coside does occur. Further, if the sugar moiety
in the C-glycopyranoside does not contain a
2%-hydroxy group, no acetyl transfer occurs.
The regioselective acetyl transfer is the result
of an optimum distance between the phenolic
hydroxyl groups of aglycon and the 2%-hy-
droxyl group of the sugar.
1
trix. H NMR and 13C NMR spectra were
recorded on Varian Inova 500 instruments
using Me4Si as the internal reference.
3-Acetoxy-4-acetyl-1,5-dibenzyloxy-2-C-
(2,3,4,6-tetra-O-benzyl-i- -glucopyranosyl)-
D
benzene (4a).—Compound 3a [9] (449 mg,
0.515 mmol) was dissolved in Ac2O (5 mL)
and pyridine (1 mL), and DMAP (10 mg) was
then added. The mixture was stirred at room
temperature (rt) for 1 day, and the reaction
mixture was then poured into 1 M HCl and
extracted with EtOAc. The extracts
1. Experimental
General methods.—All nonaqueous reac-
tions were carried out under an atmosphere of
dry argon using freshly distilled solvents, un-
less otherwise noted. All reactions were moni-

132
T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
reduced pressure. The residue was dissolved in
EtOH (10 mL), and silica gel (1 g) was then
added. The mixture was refluxed for 1 h. After
cooling, the reaction mixture was filtered, and
the filtrate was concd under reduced pressure
to give crude 5a. Crude 5a was chro-
matographed on a Polyamide® (Wako) to give
5a (88 mg, quant) as colorless crystals: mp
141–142 °C; [h]D22+46.0° (c 0.10, EtOH); Rf
were washed with water and brine, dried over
anhyd MgSO4, and concd under reduced pres-
sure. The product was chromatographed on a
silica gel column (5:1 hexane–EtOAc) to af-
ford 4a (470 mg, quant) as a colorless, highly
viscous oil: [h]D22+50.0° (c 0.10, CHCl3); Rf
0.18 (5:1 hexane–EtOAc); IR (KBr): 3088,
3062, 3030, 3008, 2981, 2920, 2868, 1956,
1878, 1772, 1691, 1606, 1585, 1497, 1454,
1429, 1365, 1323, 1311, 1252, 1203, 1159,
1093, 1070, 1028, 1011, 912, 883, 810, 737
0.60
(25:35:5:1
Me2CO–EtOAc–H2O–
AcOH); IR (KBr): 3388, 2929, 1726, 1628,
1510, 1454, 1408, 1367, 1257, 1173, 1084,
1
cm−1; H NMR (CDCl3): l 2.06 (s, 3 H,
1
1043, 997, 980, 905, 825, 756 cm−1; H NMR
ꢀOAc), 2.46 (s, 3 H, ArAc), 3.43 (ddd, 1 H, J
1.5, 2.9, 9.5 Hz, H-5%), 3.64 (dd, 1 H, J 1.5,
10.5 Hz, H-6%a), 3.72 (t, 1 H, J 9.5 Hz, H-3%),
3.76 (dd, 1 H, J 2.9, 10.5 Hz, H-6%b), 3.81 (t,
1 H, J 9.5 Hz, H-4%), 4.12 (dd, 1 H, J 9.5 9.8
Hz, H-2%), 4.15 (d, 1 H, J 11.2 Hz, benzylic
CH2), 4.44 (d, 1 H, J 11.7 Hz, benzylic CH2),
4.53 (d, 1 H, J 11.7 Hz, benzylic CH2), 4.62
(d, 1 H, J 11.2 Hz, benzylic CH2), 4.66 (d, 1
H, J 10.5 Hz, benzylic CH2), 4.86 (d, 1 H, J
11.0 Hz, benzylic CH2), 4.88 (d, 1 H, J 13.3
Hz, benzylic CH2), 4.90 (d, 1 H, J 10.5 Hz,
benzylic CH2), 4.929 (d, 1 H, J 9.8 Hz, H-1%),
4.931 (d, 1 H, J 11.0 Hz, benzylic CH2), 4.95
(d, 1 H, J 13.3 Hz, benzylic CH2), 5.00 (d, 1
H, J 12.1 Hz, benzylic CH2), 5.03 (d, 1 H, J
12.1 Hz, benzylic CH2), 6.34 (s, 1 H, ArH),
6.99–7.38 (m, 30H, ArH); FAB+MS: m/z 913
[M+H]+. Anal. Calcd for C58H56O10: C,
76.30; H, 6.18. Found: C, 76.10; H, 6.27.
(Me2SO-d6 at 40 °C): l 1.74 (s, 3 H, ꢀOAc),
2.55 (s, 3 H, ArAc), 3.18–3.26 (m, 2 H, H-4%,
5%), 3.38 (dt, 1 H, J 5.1, 9.5 Hz, H-3%), 3.45 (m,
1 H, H-6%a), 3.69 (m, 1 H, H-6%b), 4.44 (m, 1
H, OH-6%), 4.69 (d, 1 H, J 10.0 Hz, H-1%), 4.98
(d, 1 H, J 5.1 Hz, OH-4%), 5.05 (d, 1 H, J 5.1
Hz, OH-3%), 5.33 (t, 1 H, J 9.5 Hz, H-2%), 5.90
(s, 1 H, ArH), 10.10 (br. s, 1 H, ArOH), 10.95
(br. s, 1 H, ArOH), 14.10 (br. s, 1 H, ArOH);
13C NMR (Me2SO-d6): l 20.6 (ꢀOAc), 32.4
(ArAc), 61.1 (C-6%), 70.2 (C-4%), 70.8 (C-1%),
72.3 (C-2%), 76.0 (C-3%), 81.4 (C-5%), 94.3 (C-6),
101.8 (C-4), 103.4 (C-2) 162.0 (C-3*), 164.6
(C-1*, 5*), 168.7 (ꢀOAc), 202.5 (ArAc). *,
Assignments may be interchanged. FAB+MS:
m/z 373 [M+H]+. Anal. Calcd for
C16H20O10·H2O: C, 49.23; H, 5.68. Found: C,
49.97; H, 5.57.
4-Acetyl-2-C-(i- -glucopyranosyl)-1,3,5-
D
trihydroxybenzene (6a).—A solution of 3a
(2.418 g, 2.776 mmol) and 10% palladium-on-
charcoal (120 mg) in EtOAc (15 mL) and
EtOH (40 mL) was stirred at rt for 1 day
under an atmosphere of H2. After filtering, the
filtrate was concd under reduced pressure to
give 6a (915 mg, quant) as colorless crystals:
mp 167–169 °C; [h]D22+55.2° (c 0.10, EtOH);
Rf 0.43 (25:35:5:1 Me2CO–EtOAc–H2O–
AcOH); IR (KBr): 3361, 2929, 1626, 1510,
1450, 1408, 1365, 1286, 1173, 1082, 1028, 822,
4-Acetyl-2-C-(2-O-acetyl-i-
D
-glucopyran-
osyl)-1,3,5-trihydroxybenzene (5a)
Method A. A solution of 4a (240 mg, 0.263
mmol) and 10% palladium-on-charcoal (24
mg) in EtOAc (2 mL) and EtOH (5 mL) was
stirred at rt for 1 day under an atmosphere of
H2. After filtering, the filtrate was concd under
reduced pressure, the residue was dissolved in
EtOH (10 mL), and silica gel (1 g) was then
added. The mixture was refluxed for 0.5 h.
After cooling, the reaction mixture was
filtered, and the filtrate was concd under re-
duced pressure to give 5a (96 mg, 98%) as
colorless crystals.
1
754 cm−1; H NMR (Me2SO-d6): l 2.56 (s, 3
H, ArAc), 3.08–3.17 (m, 3 H, H-3%, 4%, 5%),
3.40 (m, 1 H, H-6%a), 3.65 (d, 1 H, J 11.0 Hz,
H-6%b), 3.88 (t, 1 H, J 9.5 Hz, H-2%), 4.50 (d, 1
H, J 9.8 Hz, H-1%), 4.51 (br. s, 2 H, OH), 4.84
(br. s, 2 H, OH), 5.93 (s, 1 H, ArH), 10.10 (br.
s, 1 H, ArOH), 10.99 (br. s, 1 H, ArOH),
Method B. A solution of 4c (193 mg, 0.211
mmol) and 10% palladium-on-charcoal (20
mg) in EtOAc (2 mL) and EtOH (5 mL) was
stirred at rt for 1 day under an atmosphere of
H2. After filtering, the filtrate was concd under
13
13.83 (br. s, 1 H, ArOH); C NMR (Me2SO-
d6): l 32.4 (ArAc), 61.2 (C-6%), 70.3 (C-4%),

T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
133
70.5 (C-2%), 73.4 (C-1%), 78.8 (C-3%), 81.2 (C-5%),
94.3 (C-6), 103.8 (C-2, 4), 161.8 (C-3*), 163.7
(C-1*), 164.6 (C-5*), 202.5 (ArAc). *, Assign-
ments may be interchanged. FAB+MS: m/z
5.97 (s, 1 H, ArH), 7.05–7.39 (m, 30 H, ArH),
10.67 (br. s, 1 H, ArOH): The NOESY spectra
of 3b indicated a correlation between H-1% and
methine protons, H-2%eq, H-3% and H-5%;
FAB+MS: m/z 871 [M+H]+. Anal. Calcd
for C56H54O9: C, 77.22; H, 6.25. Found: C,
77.00; H, 6.22.
331
[M+H]+.
Anal.
Calcd
for
C14H18O9·1.5H2O: C, 47.06; H, 5.92. Found: C
47.05; H 5.75.
3-Acetoxy-4-acetyl-1,5-dibenzyloxy-2-C-
4-Acetyl-1,5-dibenzyloxy-3-hydroxy-2-C-
(2,3,4,6-tetra-O-benzyl-i- -mannopyranosyl)-
D
(2,3,4,6-tetra-O-benzyl-i- -mannopyranosyl)-
D
benzene (3b).—To a stirred mixture of 1a
(6.79 g 19.5 mmol, 3 equiv), 2,3,4,6-tetra-O-
benzene (4b).—Compound 3b (1.56 g, 1.79
mmol) was dissolved in Ac2O (20 mL) and
pyridine (2 mL), and DMAP (100 mg) was
then added. The mixture was stirred at rt for 1
day. The reaction mixture was then poured
into 1 M HCl and extracted with EtOAc. The
extracts were washed with water and brine,
dried over anhyd MgSO4, and concd under
reduced pressure. The product was chro-
matographed on a silica gel column (5:1 hex-
ane–EtOAc) to afford 4b (1.45 g, 89%) as a
colorless, highly viscous oil: [h]2D2+52.0° (c
0.10, CHCl3); Rf 0.13 (5:1 hexane–EtOAc); IR
(KBr): 3088, 3062, 3030, 3007, 2931, 2900,
2868, 1954, 1878, 1809, 1768, 1755, 1693,
1608, 1585, 1579, 1497, 1454, 1427, 1367,
1352, 1321, 1282, 1244, 1215, 1151, 1124,
1092, 1072, 1047, 1028, 912, 887, 810, 734, 698
benzyl-a- -mannopyranosyl fluoride (2b) [10]
D
,
(3.53 g, 6.51 mmol) and powdered 4 A molec-
ular sieves (6 g) in CH2Cl2 (40 mL) at
−78 °C, BF3·Et2O (1.66 mL, 13.5 mmol, 2.1
equiv) were added, and the mixture was
stirred for 15 min. The temperature was grad-
ually increased to −20 °C with stirring for 1
h, and then to rt for 30 min. After adding
water, the resulting mixture was filtered
through a Celite® pad. The filtrate was ex-
tracted with CHCl3, the organic layer was
washed with water and brine, and then dried
over anhyd MgSO4. The solvent was evapo-
rated in vacuo. The residual syrup was chro-
matographed on a silica gel column (5:1
hexane–EtOAc) to give 3b (1.564 g, 28%) as a
colorless, highly viscous oil: [a]2D2+40.2° (c
1.0, CHCl3); Rf 0.27 (3:1 hexane–EtOAc); IR
(KBr): 3307, 3088, 3062, 3030, 3007, 2927,
2900, 2868, 1954, 1881, 1810, 1701, 1618,
1594, 1497, 1454, 1429, 1365, 1350, 1309,
1270, 1261, 1225, 1207, 1155, 1099, 1028, 966,
1
cm−1; H NMR (CDCl3): l 2.11 (s, 3 H,
ArOAc), 2.47 (s, 3 H, ArAc), 3.39 (ddd, 1 H,
J 2.0, 4.2, 9.5 Hz, H-5%), 3.56 (dd, 1 H, J 3.2,
9.5 Hz, H-3%), 3.70 (dd, 1 H, J 2.0, 10.5 Hz,
H-6%a), 3.74 (dd, 1 H, J 4.2, 10.5, Hz, H-6%b),
3.88 (dd, 1 H, J 1.0, 3.2 Hz, H-2%), 4.08 (t, 1
H, J 9.5 Hz, H-4%), 4.46 (d, 1 H, J 11.7 Hz,
benzylic CH2), 4.47 (d, 1 H, J 11.7 Hz, ben-
zylic CH2), 4.49 (d, 1 H, J 12.5 Hz, benzylic
CH2), 4.56 (d, 2 H, J 11.7 Hz, benzylic CH2),
4.57 (d, 1 H, J 12.5 Hz, benzylic CH2), 4.62
(d, 1 H, J 11.7 Hz, benzylic CH2), 4.71 (d, 1
H, J 11.2 Hz, benzylic CH2), 4.78 (d, 1 H, J
1.0 Hz, H-1%), 4.84 (d, 1 H, J 11.2 Hz, benzylic
CH2), 4.89 (d, 1 H, J 11.7 Hz, benzylic CH2),
5.08 (s, 2 H, benzylic CH2), 6.29 (s, 1 H,
ArH), 7.11–7.42 (m, 30 H, ArH); FAB+MS:
m/z 913 [M+H]+. Anal. Calcd for
C58H56O10: C, 76.30; H, 6.18. Found: C, 76.09;
H, 6.27.
910, 875, 797, 735, 698 cm−1 1H NMR
;
(CDCl3): l 2.52 (s, 3 H, ArAc), 3.52 (ddd, 1
H, J 2.0, 4.6, 9.6 Hz, H-5%), 3.65 (dd, 1 H, J
2.9, 9.6 Hz, H-3%), 3.69 (dd, 1 H, J 4.6, 10.8
Hz, H-6%a), 3.73 (dd, 1 H, J 2.0, 10.8, Hz,
H-6%b), 3.98 (dd, 1 H, J 1.1, 2.9 Hz, H-2%),
4.06 (t, 1 H, J 9.6 Hz, H-4%), 4.42 (d, 1 H, J
12.0 Hz, benzylic CH2), 4.51 (d, 1 H, J 12.3
Hz, benzylic CH2), 4.552 (d, 1 H, J 10.6 Hz,
benzylic CH2), 4.553 (d, 1 H, J 11.8 Hz,
benzylic CH2), 4.57 (d, 1 H, J 12.3 Hz, ben-
zylic CH2), 4.62 (d, 1 H, J 11.8 Hz, benzylic
CH2), 4.66 (d, 1 H, J 12.0 Hz, benzylic CH2),
4.79 (d, 1 H, J 11.6 Hz, benzylic CH2), 4.85
(d, 1 H, J 11.6 Hz, benzylic CH2), 4.89 (d, 1
H, J 10.6 Hz, benzylic CH2), 4.94 (d, 1 H, J
1.1 Hz, H-1%), 5.03 (d, 1 H, J 12.1 Hz, benzylic
CH2), 5.06 (d, 1 H, J 12.1 Hz, benzylic CH2),
4-Acetyl-1,3,5-trihydroxy-2-C-(2-O-acetyl-
i- -mannopyranosyl)benzene (5b).—A solu-
D
tion of 4b (478 mg, 0.523 mmol) and 10%
palladium-on-charcoal (30 mg) in EtOAc (4

134
T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
(C-4%), 71.7 (C-2%), 74.3 (C-3%), 74.9 (C-1%), 81.9
(C-5%), 94.7 (C-6), 102.7 (C-4), 103.7 (C-2),
162.3 (C-3*), 162.4 (C-1*), 163.4 (C-5*), 202.7
(ArAc). *, Assignments may be interchanged.
FAB+MS: m/z 331 [M+H]+. Anal. Calcd
for C14H18O9·1.5H2O: C, 47.06; H, 5.92.
Found: C, 47.25; H, 5.73.
mL) and EtOH (10 mL) was stirred at rt for 1
day under an atmosphere of H2. After filter-
ing, the filtrate was concd under reduced pres-
sure to give 5b (189 mg, 97%) as colorless
crystals: mp 135–136 °C; [h]2D2+38.0° (c 0.10,
EtOH); Rf 0.60 (25:35:5:1 Me2CO–EtOAc–
H2O–AcOH); IR (KBr): 3359, 2935, 2866,
1730, 1630, 1556, 1460, 1406, 1367, 1279,
1254, 1173, 1080, 1068, 825, 756, 737, 669
4-Acetyl-2-benzyloxy-3-hydroxy-1-(tert-
butyldiphenylsilyl)oxy - 2 - C - (2,3,4,6 - tetra - O-
1
cm−1; H NMR (Me2SO-d6): l 1.85 (s, 3 H,
benzyl-i-
a stirred mixture of 1c (4.55 g, 9.16 mmol, 3
equiv), 2,3,4,6-tetra-O-benzyl-a- -glucopyr-
D
-glucopyranosyl)benzene (3c).—To
ꢀOAc), 2.55 (s, 3 H, ArAc), 3.36 (m, 1 H,
H-5%), 3.60–3.65 (m, 2 H, H-3%, 4%), 3.67–3.69
(m, 2 H, H-6%a, 6%b), 4.84 (t, 1 H, J 5.1 Hz,
OH-6%), 5.07 (d, 1 H, J 5.4 Hz, OH-4%), 5.11
(d, 1 H, J 1.2 Hz, H-1%), 5.14 (d, 1 H, J 5.6
Hz, OH-3%), 5.21 (dd, 1 H, J 1.2, 2.9 Hz, H-2%),
5.79 (s, 1 H, ArH), 9.80 (br. s, 1 H, ArOH),
11.80 (br. s, 1 H, ArOH), 13.20 (br. s, 1 H,
ArOH); 13C NMR (Me2SO-d6): l 20.4 (ꢀOAc),
32.4 (ArAc), 59.4 (C-6%), 65.6 (C-4%), 71.7 (C-
3%), 72.9 (C-2%), 74.8 (C-1%), 81.1 (C-5%), 94.5
(C-6), 99.7 (C-4), 103.6 (C-2), 161.9 (C-3*),
162.8 (C-1*, 5*), 169.2 (ꢀOAc), 202.7 (ArAc):
*, Assignments may be interchanged.
FAB+MS: m/z 373 [M+H]+. Anal. Calcd
for C16H20O10·2H2O: C, 47.06; H, 5.92.
Found: C, 47.51; H, 6.11.
D
anosyl fluoride (2c) [10] (1.66 g, 3.06 mmol)
,
and powdered 4 A molecular sieves (5 g) in
CH2Cl2 (35 mL) at −78 °C, BF3·Et2O (0.751
mL, 6.11 mmol, 2.0 equiv) were added, and
the mixture was stirred for 20 min. The tem-
perature was gradually increased to −20 °C
with stirring for 1 h, and then to rt for 30 min.
After adding water, the resulting mixture was
filtered through a Celite® pad. The filtrate was
extracted with CHCl3, the organic layer was
washed with water and brine, and then dried
over anhyd MgSO4. The solvent was evapo-
rated in vacuo. The residual syrup was chro-
matographed on a silica gel column (10:1
hexane–EtOAc) to give 3c (2.16 g, 63%) as a
colorless, highly viscous oil: [a]2D2 −4.0° (c
0.10, CHCl3); Rf 0.35 (5:1 hexane–EtOAc); IR
(KBr): 3446, 3088, 3064, 3030, 2951, 2931,
2893, 2858, 1953, 1875, 1809, 1616, 1597,
1576, 1497, 1471, 1464, 1454, 1427, 1362,
1273, 1161, 1113, 1099, 1066, 1028, 999, 908,
4-Acetyl-1,3,5-trihydroxy-2-C-(i- -manno-
D
pyranosyl)benzene (6b).—A solution of 3b
(227 mg, 0.261 mmol) and 10% palladium-on-
charcoal (20 mg) in EtOAc (2 mL) and EtOH
(4 mL) was stirred at rt for 1 day under an
atmosphere of H2. After filtering, the filtrate
was concd under reduced pressure to give 6b
(87 mg, quant) as colorless crystals: mp 155–
156 °C; [h]2D2+40.0° (c 0.10, EtOH); Rf 0.54
(25:35:5:1 Me2CO–EtOAc–H2O–AcOH); IR
(KBr): 3358, 3016, 2927, 2893, 1630, 1608,
1512, 1458, 1402, 1367, 1286, 1171, 1082,
1
876, 845, 822, 804, 735, 696 cm−1; H NMR
(CDCl3): l 1.11, 1.12 (s, 9 H, t-butyl, tau-
tomer ratio; 3:1), 2.43, 2.45 (s, 3 H, ArAc),
3.56–5.15 (m, 17 H), 5.46, 5.58 (s, 1 H, ArH),
6.97–7.79 (m, 35 H, ArH), 14.33, 14.50 (s, 1
H, ArOH); FAB+MS: m/z 1019 [M+H]+.
Anal. Calcd for C65H66O9Si: C, 76.59; H, 6.53.
Found: C, 76.62; H, 6.55.
1
1030, 820, 756, 669 cm−1; H NMR (Me2SO-
d6): l 2.56 (s, 3 H, ArAc), 3.19 (ddd, 1 H, J
2.0, 5.3, 9.6 Hz, H-5%), 3.43 (dd, 1 H, J 3.1, 9.1
Hz, H-3%), 3.522 (dd, 1 H, J 9.1, 9.6 Hz, H-4%),
3.524 (dd, 1 H, J 5.3, 11.6, Hz, H-6%a), 3.69
(dd, 1 H, J 2.0, 11.6 Hz, H-6%b), 3.73 (dd, 1 H,
J 0.9, 3.1 Hz, H-2%), 4.58 (br. s,, 1 H, OH),
4.82 (br. s, 2 H, OH), 4.89 (d, 1 H, J 0.9 Hz,
H-1%), 5.60 (br. s, 1 H, OH), 5.82 (s, 1 H,
ArH), 10.07 (s, 1 H, ArOH), 11.66 (br. s, 1 H,
ArOH), 13.19 (br. s, 1 H, ArOH); 13C NMR
(Me2SO-d6): l 32.4 (ArAc), 60.6 (C-6%), 66.2
4-Acetyl-5-benzyloxy-1,3-dihydroxy-2-C-
(2,3,4,6-tetra-O-benzyl-i- -glucopyranosyl)-
D
benzene (3c%).—To a stirred mixture of 3c (468
mg, 0.459 mmol) in 1,4-dioxane (5 mL) at
0 °C, 1% aq NaOH (3 mL) was added, and
the mixture was then stirred for 5 min. The
temperature was increased to rt with stirring
for 30 min. The reaction mixture was poured
into 1 M HCl and extracted with EtOAc.
The organic layer was washed with water
and brine, dried over anhyd MgSO4,

T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
135
3.65 (dd, 1 H, J 2.1, 11.2, Hz, H-6%b), 3.71
(dd, 1 H, J 8.8, 9.2 Hz, H-3%), 4.04 (dd, 1 H, J
9.2, 9.8 Hz, H-2%), 4.12 (d, 1 H, J 11.4 Hz,
benzylic CH2), 4.44 (d, 1 H, J 12.3 Hz, ben-
zylic CH2), 4.46 (d, 1 H, J 11.4 Hz, benzylic
CH2), 4.47 (d, 1 H, J 12.3 Hz, benzylic CH2),
4.62 (d, 1 H, J 11.2 Hz, benzylic CH2), 4.75
(d, 1 H, J 9.8 Hz, H-1%), 4.78 (d, 1 H, J 11.2
Hz, benzylic CH2), 4.79 (d, 1 H, J 11.5 Hz,
benzylic CH2), 4.82 (d, 1 H, J 11.5 Hz, ben-
zylic CH2), 5.19 (s, 2 H, benzylic CH2), 6.52 (s,
1 H, ArH), 6.91–7.48 (m, 25 H, ArH), 13.28
(br. s, 1 H, ArOH); FAB+MS: m/z 823 [M+
H]+. Anal. Calcd for C51H50O10: C, 74.43; H,
6.12. Found: C, 74.46; H, 6.11.
and then evaporated in vacuo. The residual
syrup was chromatographed on a silica gel
column (6:1 hexane–EtOAc) to give 3c% (321
mg, 89%) as a colorless, highly viscous oil:
[h]2D2+144° (c 0.10, CHCl3); Rf 0.30 (5:1 hex-
ane–EtOAc); IR (KBr): 3275, 3088, 3062,
3030, 3007, 2916, 2872, 1954, 1875, 1811,
1626, 1601, 1497, 1454, 1402, 1363, 1335,
1311, 1269, 1211, 1165, 1107, 1093, 1063,
1028, 1001, 982, 912, 840, 810, 737, 696 cm−1
;
1H NMR (CDCl3): l 2.56 (s, 3 H, ArAc), 3.60
(dt, 1 H, J 2.2, 9.6 Hz, H-5%), 3.67 (dd, 1 H, J
2.2, 10.3 Hz, H-6%a), 3.73 (t, 1 H, J 9.6 Hz,
H-2%), 3.75 (dd, 1 H, J 2.2, 10.3, Hz, H-6%b),
3.83 (t, 1 H, J 9.6 Hz, H-3%), 3.90 (t, 1 H, J 9.6
Hz, H-4%), 4.17 (d, 1 H, J 10.5 Hz, benzylic
CH2), 4.43 (d, 1 H, J 12.0 Hz, benzylic CH2),
4.53 (d, 1 H, J 11.0 Hz, benzylic CH2), 4.54
(d, 1 H, J 10.5 Hz, benzylic CH2), 4.57 (d, 1
H, J 12.0 Hz, benzylic CH2), 4.86 (d, 2 H, J
11.0 Hz, benzylic CH2), 4.97 (d, 1 H, J 11.0
Hz, benzylic CH2), 5.07 (s, 2 H, benzylic
CH2), 5.12 (d, 1 H, J 9.6 Hz, H-1%), 6.03 (s, 1
H, ArH), 7.00–7.46 (m, 25 H, ArH), 8.83 (br.
s, 1 H, ArOH), 14.61 (s, 1 H, ArOH);
FAB+MS: m/z 781 [M+H]+. Anal. Calcd
for C49H48O9: C, 75.37; H, 6.20. Found: C,
75.38; H, 6.14.
4-Acetyl-1,5-dibenzyloxy-2-C-(3,4,6-tri-O-
benzyl-2-deoxy-i- -arabino-hexopyranosyl)-
D
3-hydroxybenzene (3d).—To a stirred mixture
of 1d (506 mg 1.45 mmol, 3 equiv), 1-O-
acetyl-2-deoxy-3,4,6-tri-O-benzyl- -arabino-
D
hexopyranose (2d) [11] (231 mg, 0.485 mmol,
,
a:b=92:8) and powdered 4 A molecular
sieves (0.3 g) in CH2Cl2 (4 mL) at −45 °C,
BF3·Et2O (125 mL, 1.02 mmol, 2.1 equiv) were
added, and the mixture was stirred for 10 min.
The temperature was gradually increased to rt
with stirring for 30 min. After adding water,
the resulting mixture was filtered through a
Celite® pad. The filtrate was extracted with
CHCl3, the organic layer was washed with
water and brine, and then dried over anhyd
MgSO4. The solvent was evaporated in vacuo.
The residual syrup was chromatographed on a
silica gel column (6:1 hexane–EtOAc) to give
3d (209 mg, 56%) as a colorless, highly viscous
oil: [a]2D2 −10.0° (c 0.10, CHCl3); Rf 0.22 (5:1
hexane–EtOAc); IR (KBr): 3647, 3088, 3062,
3030, 3007, 2926, 2900, 2864, 1954, 1876,
1809, 1620, 1595, 1497, 1454, 1431, 1404,
1387, 1367, 1273, 1207, 1182, 1169, 1120,
1072, 1028, 1003, 908, 845, 797, 735, 698
1-Acetoxy-4-acetyl-5-benzyloxy-3-hydroxy-
2-C-(2,3,4,6-tetra-O-benzyl-i- -glucopyran-
D
osyl)benzene (4c).—Compound 3c% (547 mg,
0.700 mmol) was dissolved in Ac2O (5 mL)
and pyridine (0.10 mL). The mixture was
stirred at rt for 2 h. The reaction mixture was
poured into 1 M HCl and then extracted with
EtOAc. The extracts were washed with water
and brine, dried over anhyd MgSO4, and
concd under reduced pressure. The product
was chromatographed on a silica gel column
(4:1 hexane–EtOAc) to afford 4c (463 mg,
80%) as a colorless, highly viscous oil: [h]2D2+
8.0° (c 0.10, CHCl3); Rf 0.23 (5:1 hexane–
EtOAc); IR (KBr): 3653, 3088, 3062, 3030,
3008, 2916, 2868, 1954, 1875, 1778, 1608,
1497, 1454, 1427, 1396, 1365, 1311, 1271,
1192, 1147, 1103, 1068, 1028, 1007, 980, 912,
1
cm−1; H NMR (CDCl3): l 2.07 (ddd, 1 H, J
2.1, 5.2, 12.7 Hz, H-2%eq), 2.56 (s, 3 H, ArAc),
2.57 (dt, 1 H, J 12.0, 12.7 Hz, H-2%ax) 3.55
(ddd, 1 H, J 1.7, 4.4, 9.6 Hz, H-5%), 3.63 (t, 1
H, J 9.6 Hz, H-4%), 3.763 (ddd, 1 H, J 5.2, 9.6,
12.0 Hz, H-3%), 3.765 (dd, 1 H, J 1.7, 11.0, Hz,
H-6%a), 3.82 (dd, 1 H, J 4.4, 11.0 Hz, H-6%b),
4.51 (d, 1 H, J 12.4 Hz, benzylic CH2), 4.60
(d, 1 H, J 11.7 Hz, benzylic CH2), 4.61 (d, 1
H, J 10.8 Hz, benzylic CH2), 4.65 (d, 1 H, J
887, 842, 808, 735, 696 cm−1 1H NMR
;
(Me2SO-d6 at 120 °C): l 2.18 (s, 3 H, ArOAc),
2.54 (s, 3 H, ArAc), 3.51 (ddd, 1 H, J 2.1, 4.2,
9.5 Hz, H-5%), 3.58 (dd, 1 H, J 8.8, 9.5 Hz,
H-4%), 3.60 (dd, 1 H, J 4.2, 11.2 Hz, H-6%a),

136
T. Kumazawa et al. / Carbohydrate Research 320 (1999) 129–137
12.4 Hz, benzylic CH2), 4.67 (d, 1 H, J 11.7
Hz, benzylic CH2), 4.92 (d, 1 H, J 10.8 Hz,
benzylic CH2), 5.05 (d, 1 H, J 12.0 Hz, ben-
zylic CH2), 5.066 (s, 2 H, benzylic CH2), 5.071
(dd, 1 H, J 2.1, 12.0 Hz, H-1%), 5.11 (d, 1 H, J
12.0 Hz, benzylic CH2), 6.04 (s, 1 H, ArH),
7.21–7.44 (m, 25 H, ArH), 14.20 (s, 1 H,
ArOH); FAB+MS: m/z 765 [M+H]+. Anal.
Calcd for C49H48O8: C, 76.94; H, 6.32. Found:
C, 76.79; H, 6.32.
EtOAc (2 mL) and EtOH (4 mL) was stirred
at rt for 1 day under an atmosphere of H2.
After filtering, the filtrate was concd under
reduced pressure to give 5d (38 mg, 92%) as
colorless crystals: mp 156–157 °C; [h]D22
+90.0° (c 0.10, EtOH); Rf 0.55 (25:35:5:1
Me2CO–EtOAc–H2O–AcOH); IR (KBr):
3365, 2935, 2893, 1774, 1751, 1637, 1593,
1506, 1448, 1363, 1286, 1261, 1182, 1072,
1
1057, 962, 889, 852 cm−1; H NMR (Me2SO-
3-Acetoxy-4-acetyl-1,5-dibenzyloxy-2-C-
d6): l 1.68 (ddd, 1 H, J 2.2, 5.0, 10.5 Hz,
H-2%eq), 1.90 (dt, 1 H, J 10.5, 11.7 Hz, H-
2%ax), 2.20 (s, 3 H, ArOAc), 2.38 (s, 3 H,
ArAc), 3.04–3.10 (m, 2 H, H-4%, 5%), 3.41 (m,
1H, H-3%), 3.46 (ddd, 1 H, J 5.2, 5.5, 10.3 Hz,
H-6%a), 3.64 (ddd, 1 H, J 0.5, 5.2, 10.3 Hz,
H-6%b), 4.37 (t, 1 H, J 5.2 Hz, OH-6%), 4.67
(dd, 1 H, J 2.2, 11.7 Hz, H-1%), 4.85 (d, 1 H, J
4.9 Hz, OH-3%), 4.89 (d, 1 H, J 4.6 Hz, OH-4%),
6.32 (s, 1 H, ArH), 10.30 (br. s, 1 H, ArOH),
11.26 (br. s, 1 H, ArOH); 13C NMR (Me2-
SO-d6): l 20.9 (ꢀOAc), 31.3 (ArAc), 37.7 (C-
2%), 61.1 (C-6%), 70.0 (C-1%), 71.4 (C-4%), 72.0
(C-3%), 81.3 (C-5%), 100.5 (C-6), 112.2 (C-4),
112.5 (C-2), 148.8 (C-3*), 158.9 (C-1*), 159.2
(C-5*), 168.8 (ꢀOAc), 199.7 (ArAc). *, Assign-
ments may be interchanged. FAB+MS: m/z
357 [M+H]+. Anal. Calcd for C16H20O9: C,
53.93; H, 5.66. Found: C, 53.97; H, 5.80.
(3,4,6-tri-O-benzyl-2-deoxy-i- -arabino-hex-
D
opyranosyl)benzene (4d).—Compound 3d (99
mg, 0.13 mmol) was dissolved in Ac2O (5 mL)
and pyridine (1 mL), and DMAP (10 mg) was
then added. The mixture was stirred at rt for 1
day. The reaction mixture was poured into 1
M HCl and extracted with EtOAc. The ex-
tracts were then washed with water and brine,
dried over anhyd MgSO4, and concd under
reduced pressure. The product was chro-
matographed on a silica gel column (4:1 hex-
ane–EtOAc) to afford 4d (104 mg, quant) as
colorless, highly viscous oil: [h]2D2+40.0° (c
0.10, CHCl3); Rf 0.26 (3:1 hexane–EtOAc); IR
(KBr): 3087, 3062, 3032, 3008, 2814, 2866,
2075, 1956, 1878, 1770, 1689, 1606, 1585,
1497, 1454, 1429, 1365, 1313, 1250, 1203,
1182, 1161, 1147, 1092, 1074, 1028, 908, 881,
1
845, 810, 737, 696 cm−1; H NMR (CDCl3): l
2.08 (m, 1 H, H-2%a), 2.10 (s, 3 H, ArOAc),
2.28 (m, 1 H, H-2%b), 2.47 (s, 3 H, ArAc), 3.40
(m, 1 H, H-5%), 3.65 (dd, 1 H, J 1.7, 10.5 Hz,
H-6%a), 3.67–3.72 (m, 2 H, H-3%, 4%), 3.78 (dd,
1 H, J 3.4, 10.5, Hz, H-6%b), 4.45 (d, 1 H, J
11.8 Hz, benzylic CH2), 4.55 (d, 1 H, J 11.8
Hz, benzylic CH2), 4.57 (d, 1 H, J 11.5 Hz,
benzylic CH2), 4.63 (d, 1 H, J 10.6 Hz, ben-
zylic CH2), 4.65 (d, 1 H, J 11.5 Hz, benzylic
CH2), 4.90 (dd, 1 H, J 2.0, 12.0 Hz, H-1%), 4.95
(d, 1 H, J 10.6 Hz, benzylic CH2), 4.99 (d, 1
H, J 11.7 Hz, benzylic CH2), 5.03 (d, 1 H, J
11.7 Hz, benzylic CH2), 5.05 (d, 1 H, J 12.0
Hz, benzylic CH2), 5.08 (d, 1 H, J 12.0 Hz,
benzylic CH2), 6.43 (s, 1 H, ArH), 7.22–7.40
(m, 25 H, ArH); FAB+MS: m/z 807 [M+
H]+. Anal. Calcd for C51H50O9: C, 75.91; H,
6.25. Found: C, 75.67; H, 6.18.
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