Simple preparation of phenylpropenoid β-D-glucopyranoside congeners by Mizoroki-Heck type reaction using organoboron reagents

Article abstract of DOI:10.1016/j.tet.2005.08.043

Palladium(II)-catalyzed carbon-carbon bond formation between allyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside (3) and arylboronic acid congeners gave the corresponding cinnamyl 2,3,4,6-tetra-O-acetyl- β-d-glucopyranosides (4a-m) in good yield. Among them, coupling products 4a-m were converted to not only the naturally occurring phenylpropenoid β-d-glucopyranoside analogues (1a-e) but also the unnaturally ones (1f-m).

Full text of DOI:10.1016/j.tet.2005.08.043

Tetrahedron 61 (2005) 10559–10568
Simple preparation of phenylpropenoid b-D-glucopyranoside
congeners by Mizoroki–Heck type reaction using
organoboron reagents
Masashi Kishidaa,b and Hiroyuki Akitaa,
*
aSchool of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274, Japan
bTsukuba Research Institute, Novartis Phrma. K.K., 8, Ohkubo, Tsukuba-shi, Ibaraki 300-2611, Japan
Received 27 June 2005; accepted 3 August 2005
Available online 6 September 2005
Abstract—Palladium(II)-catalyzed carbon–carbon bond formation between allyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (3) and
arylboronic acid congeners gave the corresponding cinnamyl 2,3,4,6-tetra-O-acetyl- b-D-glucopyranosides (4a–m) in good yield. Among
them, coupling products 4a–m were converted to not only the naturally occurring phenylpropenoid b-D-glucopyranoside analogues (1a–e)
but also the unnaturally ones (1f–m).
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
methoxycinnamyl O-b-D-glucopyranoside; 1d) have been
isolated from Citrus unshiu as an antihypertensive
ingredient,5a,d and Icariside H1 (3,4,5-trimethoxycinnamyl
Golden root (Roseroot, Rhodiola rosea L., Crassulaceae)
has been used for a long time as a resource in Chinese
traditional medicine.2 Phenylpropenoid Glucoside, such as
Rosin3 (cinnamyl O-b-D-glucopyranoside; 1a), was isolated
from R. rosea3ab as one of the major active ingredients and
reported to be pharmacologically active as antioxidants and
neurostimulants.3d Moreover, some other phenylpropenoid
glucoside analogues have been isolated as bioactive
substances. For instance, Sachaliside 14 (Triandrin;
4-hydroxycinnamyl O-b-D-glucopyranoside; 1b) and
Vimalin4c,d (4-methoxycinnamyl O-b-D-glucopyranoside;
1c) have been isolated from the callus cultures of the
plant.4c In addition, Citrusin D3c,5 (Coniferin; 4-hydroxy-3-
O-b-D-glucopyranoside;
Sagittatuma6a (Scheme 1).
1e),6
from
Epimedium
Meanwhile, some syntheses of phenylpropenoid glycoside
derivatives have been reported. Matsui et al. reported the
synthesis of Citrusin D (1d) using silica gel-catalyzed b-O-
glucosilation of the 3-methoxy-4-(tetrahydropyra-2-yloxy)-
cinnamylalcohol and the 1,2-anhydro-3,4,6-tri-O-pivaloyl-
b-D-glucopyranose as a key reaction.7 Recently, we have
reported that the coupling of cinnamyl alcohol derivatives
and 4-nitrophenyl-b-D-glucopyranoside using b-glucosidase
(EC 3.2.1.21) in a phosphate buffer (pH 5) gave Rosin (1a)
Scheme 1.
Keywords: Mizoroki–Heck type reaction; Rhodiola rosea; Cinnamyl ethers.
*
Corresponding author. Tel.: C81 474 72 1805; fax: C81 474 76 6195; e-mail: akita@phar.toho-u.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.043

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M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
Scheme 2. Regents and conditions: (a) allyl alcohol, H2O, immobilized b-glucosidase with ENTP-4000, 50 8C, 72 h, 68%; (b) Ac2O, cat. DMAP, pyridine, rt,
overnight, quant.; (c) organoboron reagents, cat. Pd(OAc)2, Cu(OAc)2, LiOAc, DMF, 80–100 8C, 0.5–1.5 h, 42–86%; (d) K2CO3, MeOH, rt, 1 h or NaOMe,
MeOH, rt, 1 h 63–99%.
and Vimalin (1c).8 However, to synthesize the diverse
phenylpropenoid glucoside analogues using existing
glucosilation methods, many kinds of substituted cinnamyl-
alcohols should be synthesized. On the other hand, cross-
metathesis could be a useful method to prepare phenyl-
propenoid glucoside analogues. In fact, Chi-Huey et al.
reported the synthesis of some phenylpropenoid galactoside
analogues from tetra-O-acetyl-a-D-allyl-galactoside and
substituted styrene via cross-methathesis.9 It was an
effective method to synthesize a structurally diverse
phenylpropenoid library; however, an excess amount of
styrenes was required to avoid the production of self-
metathesis of tetra-O-acetyl-a-D-allyl-galactoside as a by-
product. Therefore, other methods to prepare diverse
phenylpropenoid analogues including natural ones were
expected for investigation of their biological activities. We
herein report a simple total synthesis of Rosin (1a),
Sachaliside 1 (Triandrin; 1b), Vimalin (1c), Citrusin D
(Coniferin; 1d), and Icariside H1 (1e) using the Mizoroki–
Heck (MH) type reaction between the substituted
arylboronic acid congeners and allyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (3) under Pd(II) condition as
the key reaction (Scheme 2, step c).
disclosed that the phenylboronic acid reacted with several
olefins other than enones and enals, such as allyl phenyl
ether, to give the corresponding coupling products via the
Pd(II)-catalyzed MH type reaction. However, only one
example of the reaction of allyl ether with phenylboronic
acid was examined in this literature and no other examples
have been reported in the field of carbohydrate chemistry.
Furthermore, we synthesized not only naturally occurring
but also unnaturally occurring phenylpropenoid analogues
to investigate the limitation of this strategy.
2. Results
2.1. Synthesis of substrate for MH type reaction and
4-hydroxy-3-methoxyphenylboronic acid
Some syntheses of allyl 2,3,4,6-tetra-O-acetyl-b-D-gluco-
pyranoside (3)14 and the direct glucosidation of D-glucose
using b-glucosidase (EC 3.2.1.21) from almonds have been
reported.15 Meanwhile, we had reported direct b-glucosi-
dation between D-glucose and primary alcohol using the
immobilized b-glucosidase (EC 3.2.1.21) from almonds
with the synthetic prepolymer ENTP-4000 gave mono-b-
glucopyranoside in moderate yield.16 As in the previous
method, the allyl b-D-glucopyranoside (2) was prepared
from D-glucose and allyl alcohol using the immobilized
b-glucosidase in 68% yield. The immobilized b-glucosidase
was reusable and the yield of 2 was 55% in the case of using
recovered immobilized b-glucosidase. Acetylation of 2 with
acetic anhydride in pyridine afforded allyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (3) as a key substrate for MH
type reaction. In the meantime, 4-hydroxy-3-methoxy-
phenylboronic acid (7) was prepared as shown in Scheme 3.
Tetrahydro-pyranyl (THP) protection of the 4-bromoguaicol
using dihydropyran (DHP) and 4 M HCl in EtOAc gave
3-methoxy-4-(tetrahydropyra-2-yloxy)-1-bromobenzene
(6) in 75% yield. To a solution of n-BuLi in THF/n-hexane
at K78 8C was slowly added a THF solution of 6, then the
The synthesis of cinnamyl ethers using the MH-type
arylation of allyl ethers with aryl iodides was reported by
Tamaru et al.10 However, the isolated yield was moderate
(22–57%) and substantial quantities of benzyl vinyl ethers
and 2-phenyl allyl ether (8–43%) were provided as by-
products. The MH-type reaction of phenylboronic acids and
conjugated olefins, such as butyl acrylate, acrylnitrile, and
methyl vinyl ketone under Pd(0)-catalyzed condition was
shown by Cho and Uemura.11a Moreover, they reported that
phenylantimonyl chlorides react smoothly with alkenes in
the presence of Pd(II) acetate11b and Hiyama et al. also
reported arylsilanols or aryltin reagents undergo the MH
type reaction under Pd(II) condition.12 On the other hand,
organoboron-mediated MH type reaction via a Pd(II)-
species had been also reported by Mori et al.13 They
Scheme 3. Reagents and conditions: (e) DHP, 4 M HCl in EtOAc, EtOAc, rt, 12 h, 75%; (f) (i) n-BuLi, THF, K78 8C; (ii) B(O-i-Pr)3; (iii) 1 M HCl aqueous,
91%.

M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
10561
Table 1. Reaction of arylboronic acid with 2,3,4,6-tetra-O-accetyl-b-D-
glucopyranoside (3)a
and phenols were obtained as by-products. Moreover, the
reaction of 3 and 4-hydroxy-3-methoxyphenyl boronic acid
was carried out at 80 8C due to the thermolability of the
coupling product 4d (entry 4). In fact, 4d was decomposed
rapidly at 100 8C under the coupling condition.
Entry
Ar-B(OH)2 (ArZ)
Product (%
yield)
1
2
3
4
5
6
7
8
Phenyl
4a (71)
4b (62)
4c (72)
4d (52)
4e (67)
4f (86)
4g (74)
4h (42)
4i (74)
4j (75)
4k (45)
4l (63)
4m (53)
4-Hydroxyphenylb
4-Methoxyphenyl
4-Hydroxy-3-methoxyphenylc
3,4,5-Trimepthoxyphenyl
3-Methoxyphenyl
2-Methoxyphenyl
3,4-Dimethoxyphenyl
4-Chlorophenyl
After deprotection of substituted cinnamyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranosides (4a–4n) using NaOMe/MeOH
or K2CO3/MeOH, many kinds of the desired phenyl-
propenoid glycoside analogues (1a–1m) were provided
rapidly. It should be noted that Citrusin D (Coniferin; 1d)
was unstable, therefore, evaporation of 1d was required to
be performed at under 5 8C. The spectral data (1H and 13C
NMR) and specific rotation {[a]D} of synthetic natural-type
phenylpropenoid glycoside analogues (1a, 1b, 1c, 1d, and
1e) were identical with those of natural products.
9
10
11
12
13
4-Cyanophenyl
4-Trifluoromethylphenyl
3-Nitorphenyl
b-Naphtyl
a Unless otherwise noted, all coupling reactions were carried out in DMF
(4 mL), using 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (3; 1.0 mmol),
Ar-B(OH)2 (1.2 mmol), Pd(OAc)2 (0.1 mmol), Cu(OAc)2 (2 mmol), and
LiOAc (3 mmol) at 100 8C for 1.5 h.
b Coupling reaction was carried out in DMF (8 mL), using 2,3,4,6-tetra-O-
b-D-glucopyranoside (3; 2.0 mmol), Ar-B(OH)2 (6.0 mmol), Pd(OAc)2
(0.2 mmol), Cu(OAc)2 (10 mmol), and LiOAc (10 mmol) at 80 8C for
0.5 h.
3. Discussion
The MH-type reaction of silanols and organotin compounds
with olefins via a Pd(II)-mediated pathway has been
reported by Hiyama and co-workers.12 Based on this
pathway, a plausible MH type reaction mechanism with
arylboronic acids had been presented by us.1 According to
this mechanism, the aryl unit migrated to the palladium
center from arylboronic acid to furnish an aryl palladium
species first, and this reactive aryl palladium species was
added to an olefin of allyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (3) to afford an intermediate A. After
reductive b-elimination of the intermediate A, the desired
product was obtained along with the release of
palladium(0). Finally, the palladium(0) species was
oxidized by a combination of copper(II) acetate and lithium
acetate to regenerate palladium(II) as the key species of this
catalytic reaction. The MH type arylation of allyl ethers
with aryl halides was reported to give some regioisomers as
by-products.10 Taking into account for this reference in the
present case, undesired products B and D via path B and
path D, respectively, as shown in Scheme 4 are considered
as by-products. Indeed, the 1H NMR analysis of crude
products indicated that a little amount of regioisomers (less
than 5%) might be provided as by-products. However, these
by-products could be easily removed by the following
purifications. Moreover, the treatment of allyl 2,3,4,6-tetra-
O-acetyl-b-D-glucopyranoside (3) and phenylboronic acid
in the presence of tetrakistriphenylphosphine palladium(0)
c Coupling reaction was carried out in DMF (4 mL), using 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (3; 1.0 mmol), Ar-B(OH)2 (3.0 mmol),
Pd(OAc)2 (0.1 mmol), Cu(OAc)2 (5 mmol), and LiOAc (5 mmol) at
80 8C for 0.5 h.
mixture was treated with a triisopropyl borate to provide the
desired 7 in 91% yield.
2.2. Synthesis of phenylpropenoid b-D-glucopyranoside
using MH-type reaction
As summarized in Table 1, we examined the coupling
reaction of various phenylboronic acids with 3. The MH-
type reaction was carried out using the substrate 3 (1 mmol),
substituted phenylboronic acids (1.2 mmol), Cu(OAc)2
(2.0 mmol), LiOAc (3.0 mmol) in the presence of
10 mol% Pd(OAc)2 in DMF (4.0 mL) at 100 8C for 1.5 h.
All phenylboronic acids having an electron-donating group
(entry 3, 5–8) and an electron-withdrawing group (entry
9–12) underwent MH-type reactions smoothly in reasonable
yield. However, 3.0 equiv of phenylboronic acid having a
non-protected hydroxyl (entry 2, 4) group at the 4-position
with 5.0 equiv of Cu(OAc)2 and LiOAc were needed to
proceed the coupling reaction. Because the deborilation of
phenylboronic acids was occurred in this coupling condition
Scheme 4. The plausible MH type reaction pathway with arylboronic acid.

10562
M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
effected removal of the allyl group instead of the desired
MH-type reaction. In addition, non-protected allyl b-D-
glucopyranoside (2) could be reacted with arylboronic acid
under the same conditions. However, the chemical yield was
poor due to low conversion. For instance, when allyl b-D-
glucopyranoside (2) was treated with phenylboronic acid in
the presence of LiOAc, Cu(OAc)2, and a catalytic amount of
Pd(OAc)2 in DMF at 100 8C for 5 h, the desired cinnamyl
b-D-glucopyranoside (1a) could be obtained in only 11%
yield along with a large amount of the starting material. This
phenomenon might be explained by the deactivation of
arylboronic acid due to the formation of arylboronic ester
from arylboronic acid and allyl b-D-glucopyranoside (2). In
fact, the 4-hydroxyphenylboronic acid could be reacted with
3 in 62%; however, 4,4,5,5-tetramethyl-2- (4-hydroxy-
phenyl)-1,3-dioxaborane failed to react under the same
conditions. This result suggested that an arylboronic ester
was less reactive than an arylboronic acid with the allyl
ether 3 in this case.
mg). The preparation of the immobilized b-D-glucosidase
from almonds on the photocross-linkable resin prepolymer
(ENTP-4000) was carried out using the following pro-
cedure. One gram of ENTP-4000 was mixed with 10 mg of
photosensitizer, benzoin ethyl ether, and 74 mg of b-D-
glucosidase from almonds (3.4 units/mg). The mixture was
layered on a sheet of transparent polyester film (thickness,
ca. 0.5 mm). The layer was covered with transparent thin
film and then illuminated with chemical lamps (wavelength
range, 300–400 nm) for 3 min. The gel film thus obtained
was cut into small pieces (0.5!0.5!5 mm) and used for
the bioconversion reaction.
5.2.1. Allyl b-D-glucopyranoside (2). A mixture of
D-glucose (1.1 g, 6.1 mmol), water (2 mL), allyl alcohol
(18 mL), and the immobilized b-D-glucosidase (250 units)
was incubated for 3 days at 50 8C. The reaction mixture was
filtered off and the recovered immobilized b-D-glucosidase
was washed with water (4 mL) and AcOEt (7 mL). The
combined filtrate was directly chromatographed on silica
gel (35 g) to give 2 (0.91 g, 68%) as a colorless crystal from
the CHCl3/MeOHZ9:1 eluent. Mp: 101–103 8C; [a]D28
K41.4 (c 0.43, MeOH); IR (KBr) 3385, 1645, 1415,
1074 cmK1; 1H NMR (D2O-acetone-d6, 400 MHz) d: 5.90–
5.80 (m, 1H), 5.25 (d, JZ17.6 Hz, 1H), 5.16 (d, JZ10.3 Hz,
1H), 4.37 (d, JZ7.8 Hz, 1H), 4.26 (dd, JZ6.6, 12.7 Hz,
1H), 4.10 (dd, JZ6.6, 12.7 Hz, 1H), 3.78 (dd, JZ5.9,
12.2 Hz, 1H), 3.58 (dd, JZ5.9, 12.2 Hz, 1H), 3.36 (t, JZ
9.3 Hz, 1H), 3.31 (m, 1H), 3.25 (m, 1H), 3.15 (m, 1H); 13C
NMR (D2O-acetone-d6, 100 MHz) d: 134.2, 119.5, 102.0,
76.7, 76.6, 74.0, 71.4, 70.5, 61.6. Anal. Found: C, 49.01; H,
7.36%. Calcd for C9H16O6: C, 49.08; H, 7.32%.
4. Conclusion
In conclusion, natural phenylpropenoid glucopyranosides,
such as Rosin (1a), Sachaliside 1 (Triandrin; 1b), Vimalin
(1c), Citrusin D (Coniferin; 1d), and Icariside H1 (1e), have
been prepared based on the MH type reaction using the
substituted arylboronic acid congeners. Moreover,
structurally diverse unnatural phenylpropenoid gluco-
pyranoside analogues (1f–1m) were also obtained. There-
fore, this strategy is effective to prepare a variety of
phenylpropenoid glucopyranoside congeners using a
number of commercially available substituted arylboronic
acids.
5.2.2. Allyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside
(3). A mixture of 2 (0.50 g, 2.3 mmol), Ac2O (1.85 g,
18.1 mmol), 4-N,N-dimethylaminopyridine (DMAP;
10 mg, 0.08 mmol) in pyridine (2 mL) was stirred for 1 h
at room temperature. The reaction mixture was diluted with
water and extracted with AcOEt. The organic layer was
washed with 10% aqueous HCl and brine. The organic layer
was dried over MgSO4 and evaporated to give a residue,
which was chromatographed on silica gel (20 g) to afford 3
(0.88 g, quantitative yield) as colorless needles from the
n-hexane/AcOEtZ3:1 eluent. Mp: 83–88 8C; [a]2D5 K26.1
(c 0.96, CHCl3); IR (KBr) 3379, 2945, 1751, 1228,
5. Experimental
5.1. General
All melting points were measured on a Yanaco MP-3S
1
micro melting point apparatus and are uncorrected. H and
13C NMR spectra were recorded on JEOL AL 400
spectrometer or Bruker 400 spectrometer in CDCl3,
methanol-d4, DMSO-d6, D2O and pyridine-d5 with Me4Si
as an internal reference. High-resolution mass spectra
(HRMS) and the fast atom bombardment mass spectra
(FAB MS) were obtained with a JEOL JMS 600H
spectrometer. IR spectra were recorded with a JASCO FT/
IR-300 spectrometer. Optical rotations were measured with
a JASCO DIP-370 digital polarimeter. All reagents were
purchased from commercial sources and were used without
purification. All evaporations were performed under
reduced pressure. For column chromatography, silica gel
(Kieselgel 60) was employed and for flash column
chromatography, silica gel (Silica Gel 60N, spherical,
neutral, 40–50 mm) was employed.
1
1042 cmK1; H NMR (CDCl3, 400 MHz) d: 5.90–5.80 (m,
1H), 5.27 (dd, JZ1.6, 17.2 Hz, 1H), 5.21 (t, JZ9.5 Hz, 1H),
5.21 (dd, JZ1.6, 10.8 Hz, 1H), 5.10 (d, JZ9.5 Hz, 1H),
4.03 (dd, JZ8.0, 9.5 Hz, 1H), 4.56 (d, JZ8.0 Hz, 1H), 4.34
(dd, JZ5.0, 13.1 Hz, 1H), 4.27 (dd, JZ4.7, 12.2 Hz, 1H),
4.15 (dd, JZ2.4, 12.2 Hz, 1H), 4.10 (dd, JZ6.4, 13.1 Hz,
1H), 3.69 (ddd, JZ2.4, 4.7, 9.5 Hz, 1H), 2.09 (s, 3H), 2.05
(s, 3H), 2.02 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3,
100 MHz) d: 170.7, 170.3, 169.4, 169.3, 133.3, 117.7, 99.6,
72.9, 71.8, 71.3, 70.0, 68.5, 62.0, 20.7, 20.7, 20.6. Anal.
Found: C, 52.49; H, 6.29%. Calcd for C17H24O10: C, 52.58;
H, 6.23%.
5.2. Immobilization of b-D-glucosidase using a
prepolymer
5.2.3. 2-(4-Bromo-2-methoxyphenoxy)tetrahydropyran
(6). A mixture of 4-bromoguaicol (4.06 g, 0.020 mmol)
and dihydropyrane (DHP; 16.80 g, 0.20 mmol) in AcOEt
(40 mL) was treated with 4 M HCl in AcOEt (3 mL) and
stirred at room temperature for 24 h. The mixture was
b-D-Glucosidase (EC 3.2.1.21) from almonds was pur-
chased from Sigma Chemical Co. (G-0395, 2.5–3.6 units/

M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
10563
poured into saturated NaHCO3 aqueous solution and the
organic layer was washed with brine, dried over MgSO4,
and evaporated in vacuo. The residue was purified by flash
chromatography to afford 6 (4.31 g, 75%) as colorless
syrup. IR (KBr) 2944, 1469, 1253, 1221, 1030, 958, 916,
5.0, 10.1 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H),
2.01 (s, 3H); 13C NMR (CDCl3, 100 MHz) d: 170.7, 170.3,
169.4, 169.3, 136.3, 133.1, 128.6, 127.9, 126.5, 124.5, 99.5,
72.9, 71.8, 71.3, 69.8, 68.4, 62.0, 20.7, 20.59, 20.57. Anal.
Found: C, 59.40; H, 6.05%. Calcd for C23H28O10: C, 59.48;
H, 6.08%.
1
856 cmK1; H NMR (CDCl3, 400 MHz) d: 7.00 (s, 3H),
5.35 (t, JZ3.3 Hz, 1H), 3.99–3.92 (m, 1H), 3.84 (s, 3H),
3.62–3.55 (m, 1H), 2.05–1.83 (m, 3H), 1.71–1.60 (m, 3H);
13C NMR (CDCl3, 100 MHz) d: 151.1, 145.6, 123.6, 119.2,
115.7, 114.5, 97.7, 62.1, 56.2, 30.3, 25.2, 18.7. Anal. Found:
C, 50.03; H, 5.12%. Calcd for C12H15BrO3: C, 50.19; H,
5.27%.
5.3.2. 4-Hydroxycinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4b). A mixture of allyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (0.78 g, 2.0 mmol), 4-hydroxy-
phenylboric acid (0.82 g, 6.0 mmol), copper(II) acetate
(1.81 g, 10 mmol), lithium acetate (0.66 g, 10 mmol) and
palladium(II) acetate (0.044 g, 0.20 mmol) in DMF
(8.0 mL) was stirred for 0.5 h at 80 8C. Allowed to cool to
room temperature, the reaction mixture was diluted with
EtOAc and washed with 1 M HCl and brine. The organic
layer was evaporated to dryness and the residue was purified
by flash column chromatography to afford 4b (0.60 g, 62%)
as a white solid. The white solid was recrystallized from
ether/n-hexane to give 4b (0.50 g, 52%), a pure colorless
needle to be analyzed by microanalyses. Mp: 146.0–
147.0 8C; [a]2D9 K31.5 (c 0.47, MeOH); IR (KBr) 3370,
1754, 1713, 1609, 1514, 1442, 1371, 1227, 1170, 1043, 972,
5.2.4. 4-Hydroxy-3-methoxyphenylboronic acid (7). A
solution of n-buthyllithium in hexane (1.5 M, 9.7 mL,
14.6 mmol) was added to THF (30 mL), keeping the
temperature below K60 8C. 2-(4-Bromo-2-methoxy-
phenoxy)tetrahydropyran 6 (3.80 g, 13.2 mmol) dissolved
in THF (8.0 mL) was added, keeping the temperature below
K65 8C during the addition. After 10 min at this tempera-
ture triisopropyl borate (6.10 mL, 26.5 mmol) was added
neat at K65 8C. The mixture was stirred at the same
temperature for 10 min, quenched by addition of 1 N HCl
aqueous solution and extracted with EtOAc. The organic
layer was washed with brine, dried over MgSO4 and
evaporated in vacuo. The product was collected by filtration
and washed with CH2Cl2/hexane (1:1), and dried in vacuo to
give 7 (2.02 g, 91%) as a white solid, which was used for the
next reaction without further purification. IR (KBr) 3285,
1599, 1520, 1421, 1341, 1264, 1232, 1162, 1096, 1033, 881,
1
913, 843, 625 cmK1; H NMR (CDCl3, 400 MHz) d: 7.25
(d, JZ8.6 Hz, 2H), 6.79 (d, JZ8.6 Hz, 2H), 6.50 (d, JZ
16.1 Hz, 1H), 6.05 (ddd, JZ5.5, 6.6, 15.6 Hz, 1H), 5.45 (s,
1H), 5.22 (t, JZ9.6 Hz, 1H), 5.09 (t, JZ9.6 Hz, 1H), 5.05
(dd, JZ8.1, 9.6 Hz, 1H), 4.62 (d, JZ8.1 Hz, 1H), 4.46 (dd,
JZ5.5, 12.6 Hz, 1H), 4.29–4.22 (m, 2H), 4.17 (dd, JZ2.0,
12.1 Hz, 1H), 3.70 (ddd, JZ2.5, 4.5, 9.6 Hz, 1H), 2.09 (s,
3H), 2.05 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d: 170.9, 170.4, 169.5, 169.4, 155.7,
133.0, 129.1, 127.9, 122.0, 115.5, 99.4, 72.9, 71.8, 71.4,
70.1, 68.4, 62.0, 20.72, 20.71, 20.60, 20.57. Anal. Found: C,
57.29; H, 5.97%. Calcd for C23H28O11: C, 57.50; H, 5.87%.
1
819, 672 cmK1; H NMR (CDCl3, 400 MHz) d: 7.81 (dd,
JZ1.0, 8.0 Hz, 1H), 7.26 (d, JZ1.0 Hz, 1H), 7.06 (d, JZ
8.0 Hz, 1H), 6.00 (s, 1H), 4.03 (s, 3H); 13C NMR (CDCl3,
100 MHz) d: 146.6, 145.7, 121.5, 120.1, 114.5, 110.7, 55.9.
5.3. General procedure for MH-type reaction of
arylboronic acids with allyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (3)
5.3.3. 4-Methoxycinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4c). Obtained in 72% yield as a white
solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4c in 35% yield, a pure white solid to be
analyzed by microanalyses. Mp: 81.5–83.0 8C; [a]2D7 K28.4
(c 0.18, MeOH); IR (KBr) 1744, 1514, 1370, 1228,
A mixture of allyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
side 3 (0.39 g, 1.0 mmol), arylboronic acids (1.2 mmol),
copper(II) acetate (0.36 g, 2.0 mmol), lithium acetate
(0.20 g, 3.0 mmol) and palladium(II) acetate (0.022 g,
0.10 mmol) in DMF (4 mL) was stirred for 1.5 h at
100 8C. Allowed to cool to room temperature, the reaction
mixture was diluted with AcOEt and washed with 1 M HCl
and brine. The organic layer was evaporated to dryness and
the residue was purified by flash column chromatography on
silica gel (n-hexane/AcOEt as an eluent) to afford the
corresponding product.
1
1040 cmK1; H NMR (CDCl3, 400 MHz) d: 7.31 (d, JZ
8.6 Hz, 2H), 6.86 (d, JZ8.6 Hz, 2H), 6.53 (d, JZ15.6 Hz,
1H), 6.07 (ddd, JZ5.5, 6.6, 15.6 Hz, 1H), 5.21 (t, JZ
9.6 Hz, 1H), 5.11 (t, JZ9.6 Hz, 1H), 5.04 (dd, JZ7.6,
9.6 Hz, 1H), 4.62 (d, JZ7.6 Hz, 1H), 4.47 (ddd, JZ1.5, 5.5,
13.1 Hz, 1H), 4.30 (ddd, JZ1.0, 6.6, 13.1 Hz, 1H), 4.26 (dd,
JZ5.0, 12.1 Hz, 1H), 4.25 (dd, JZ2.5, 12.1 Hz, 1H), 3.81
(s, 3H), 3.70 (ddd, JZ2.5, 5.0, 9.6 Hz, 1H), 2.09 (s, 3H),
2.05 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3,
100 MHz) d: 170.7, 170.3, 169.4, 169.3, 159.5, 133.0,
129.1, 127.7, 122.1, 114.0, 99.4, 72.9, 71.8, 71.3, 70.1, 68.4,
62.0, 55.3, 20.7, 20.59, 20.57. Anal. Found: C, 57.85; H,
5.99%. Calcd for C24H30O11: C, 58.29; H, 6.12%.
5.3.1. Cinnamyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
side (4a). Obtained in 71% yield as a white solid. The white
solid was recrystallized from AcOEt/n-hexane to give 4a in
36% yield, a pure white powder to be analyzed by
microanalyses. Mp: 72.4–73.2 8C; [a]2D7 K32.1 (c 0.40,
MeOH); IR (KBr) 1746, 1443, 1371, 1228, 1169, 1134,
1042, 984, 914, 735 cmK1; 1H NMR (CDCl3, 400 MHz) d:
7.40–7.23 (m, 5H), 6.59 (d, JZ15.6 Hz, 1H), 6.22 (dt,
JZ15.6, 5.5 Hz, 1H), 5.22 (t, JZ9.6 Hz, 1H), 5.11 (t,
JZ9.6 Hz, 1H), 5.05 (dd, JZ8.0, 9.6 Hz, 1H), 4.62 (d, JZ
8.0 Hz, 1H), 4.50 (ddd, JZ1.5, 5.5, 13.1 Hz, 1H), 4.32–4.25
(m, 2H), 4.16 (dd, JZ2.0, 12.1 Hz, 1H), 3.71 (ddd, JZ2.0,
5.3.4. 4-Hydroxy-3-methoxycinnamyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (4d). A mixture of allyl
2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside 3 (0.39 g,
1.0 mmol), 4-hydroxy-3-(methoxy)phenylboric acid 7
(0.51 g, 3.0 mmol), copper(II) acetate (0.91 g, 5.0 mmol),
lithium acetate (0.33 g, 5.0 mmol) and palladium(II) acetate
(0.022 g, 0.10 mmol) in DMF (4 mL) was stirred for 0.5 h at

10564
M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
80 8C. Allowed to cool to room temperature, the reaction
mixture was diluted with EtOAc and washed with 1 M HCl
and brine. The organic layer was evaporated to dryness and
the residue was purified by flash chromatography to afford
4d (0.27 g, 52%) as a white solid. The white solid was
recrystallized from AcOEt/n-hexane to give 4d (0.22 g,
42%), a pure white powder. Mp: 185.0–187.0 8C; [a]D29
K32.6 (c 0.24, CDCl3); IR (KBr) 3399, 1753, 1517, 1370,
1228, 1129, 1040, 978 cmK1; 1H NMR (CDCl3, 400 MHz)
d: 6.91–6.85 (m, 3H), 6.51 (d, JZ15.6 Hz, 1H), 6.06 (ddd,
JZ5.5, 6.5, 15.6 Hz, 1H), 5.63 (s, 1H), 5.22 (t, JZ9.6 Hz,
1H), 5.11 (t, JZ9.6 Hz, 1H), 5.04 (dd, JZ8.0, 9.6 Hz, 1H),
4.62 (d, JZ8.0 Hz, 1H), 4.47 (ddd, JZ1.5, 5.6, 12.6 Hz,
1H), 4.30–4.23 (m, 2H), 4.17 (dd, JZ2.0, 12.1 Hz, 1H),
3.92 (s, 3H), 3.70 (ddd, JZ2.0, 4.5, 9.6 Hz, 1H), 2.08 (s,
3H), 2.05 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d: 170.7, 170.3, 169.40, 169.35, 146.6,
145.8, 133.3, 128.9, 122.1, 120.4, 114.4, 108.3, 99.5, 72.9,
71.8, 71.4, 70.1, 68.4, 62.0, 55.9, 20.72, 20.60, 20.59;
HR-MS (FAB-MS) m/z: 511.1840 (MC1)C; Calcd for
C24H30O12 m/z: 511.1815 (MC1)C.
5.3.7. 2-Methoxycinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4g). Obtained in 74% yield as a white
solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4g in 42% yield, pure colorless needles to
be analyzed by microanalyses. Mp: 88.9–89.5 8C; [a]D27
K25.1 (c 0.33, MeOH); IR (KBr) 1745, 1372, 1224, 1046,
984 cmK1; 1H NMR (CDCl3, 400 MHz) d: 7.42 (dd, JZ1.5,
7.6 Hz, 1H), 7.25–7.22 (m, 1H), 6.95–6.86 (m, 3H), 6.21
(ddd, JZ5.7, 7.0, 16.1 Hz, 1H), 5.21 (t, JZ9.6 Hz, 1H),
5.11 (t, JZ9.6 Hz, 1H), 5.05 (dd, JZ8.1, 9.6 Hz, 1H), 4.63
(d, JZ8.1 Hz, 1H), 4.49 (ddd, JZ1.5, 5.6, 13.1 Hz, 1H),
4.30 (ddd, JZ1.0, 6.5, 13.1 Hz, 1H), 4.27 (dd, JZ5.0,
12.6 Hz, 1H), 4.16 (dd, JZ2.5, 12.1 Hz, 1H), 3.85 (s, 3H),
3.70 (dd, JZ2.5, 5.0, 9.6 Hz, 1H), 2.09 (s, 3H), 2.06 (s, 3H),
2.02 (s, 3H), 2.00 (s, 3H); 13C NMR (CDCl3, 100 MHz) d:
170.7, 170.3, 169.39, 169.38, 156.7, 129.0, 128.4, 127.0,
125.4, 124.9, 120.7, 110.8, 99.2, 72.9, 71.8, 71.3, 70.2, 68.4,
62.0, 55.4, 20.69, 20.65, 20.60, 20.57. Anal. Found: C,
58.25; H, 6.08%. Calcd for C24H30O11: C, 58.29; H, 6.12%.
5.3.8. 3,4-Dimethoxycinnamyl 2,3,4,6-tetra-O-acetyl-b-
D-glucopyranoside (4h). Obtained in 42% yield as a white
solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4h in 32% yield, pure colorless needles to
be analyzed by microanalyses. Mp: 78.0–79.5 8C; [a]D27
K30.3 (c 0.29, MeOH); IR (KBr) 1747, 1516, 1444, 1369,
5.3.5. 3,4,5-Trimethoxycinnamyl 2,3,4,6-tetra-O-acetyl-
b-D-glucopyranoside (4e). Obtained in 67% yield as a
white solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4e in 46% yield, pure colorless needles to
be analyzed by microanalyses. Mp: 131.0–132.0 8C; [a]D29
K30.3 (c 0.29, MeOH); IR (KBr) 1752, 1583, 1506, 1422,
1371, 1335, 1228, 1128, 1043, 976 cmK1; 1H NMR (CDCl3,
400 MHz) d: 6.61 (s, 2H), 6.52 (d, JZ16.1 Hz, 1H), 6.14
(ddd, JZ5.5, 6.5, 16.1 Hz, 1H), 5.22 (t, JZ9.6 Hz, 1H),
5.12 (t, JZ9.6 Hz, 1H), 5.05 (dd, JZ8.1, 9.6 Hz, 1H), 4.63
(d, JZ8.1 Hz, 1H), 4.49 (ddd, JZ1.5, 5.5, 12.6 Hz, 1H),
4.30–4.23 (m, 2H), 4.17 (dd, JZ2.5, 12.6 Hz, 1H), 3.88 (s,
6H), 3.85 (s, 3H), 3.71 (ddd, JZ2.5, 4.5, 9.6 Hz, 1H), 2.08
(s, 3H), 2.06 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d: 170.6, 170.3, 169.4, 169.3, 153.3,
138.1, 133.0, 132.1, 124.0, 103.7, 99.6, 72.9, 71.8, 71.3,
69.8, 68.4, 61.9, 60.9, 56.2, 20.70, 20.59, 20.57. Anal.
Found: C, 56.01; H, 6.10%. Calcd for C26H35O13: C, 56.31;
H, 6.18%.
1225, 1166, 1038, 981, 609 cmK1 1H NMR (CDCl3,
;
400 MHz) d: 6.95–6.90 (m, 2H), 6.82 (d, JZ8.0 Hz, 1H),
6.53 (d, JZ16.1 Hz, 1H), 6.09 (td, JZ6.4, 16.1 Hz, 1H),
5.22 (t, JZ9.6 Hz, 1H), 5.09 (t, JZ9.6 Hz, 1H), 5.05 (dd,
JZ8.1, 9.6 Hz, 1H), 4.63 (d, JZ8.1 Hz, 1H), 4.47 (dd, JZ
5.5, 12.6 Hz, 1H), 4.29–4.23 (m, 2H), 4.17 (dd, JZ2.0,
12.6 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 3.71 (ddd, JZ2.5,
4.5, 9.6 Hz, 1H), 2.09 (s, 3H), 2.06 (s, 3H), 2.03 (s, 3H), 2.01
(s, 3H); 13C NMR (CDCl3, 100 MHz) d: 170.6, 170.3,
169.4, 169.3, 149.12, 149.05, 133.1, 129.4, 122.4, 119.8,
111.1, 108.9, 99.5, 72.9, 71.8, 71.4, 70.0, 61.9, 55.9, 55.8,
20.71, 20.59, 20.57. Anal. Found: C, 57.05; H, 6.09%. Calcd
for C25H32O12: C, 57.25; H, 6.15%.
5.3.9. 4-Chlorocinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4i). Obtained in 74% yield as a white
solid. The white solid was recrystallized from ether/
n-hexane to give 4i in 51% yield, a pure white powder to
be analyzed by microanalyses. Mp: 92.3–94.0 8C; [a]D29
K31.4 (c 0.44, CHCl3); IR (KBr) 1748, 1369, 1229, 1169,
1041, 987, 913 cmK1; 1H NMR (CDCl3, 400 MHz) d: 7.29
(s, 4H), 6.54 (d, JZ16.1 Hz, 1H), 6.19 (ddd, JZ5.5, 6.5,
16.1 Hz, 1H), 5.22 (t, JZ9.6 Hz, 1H), 5.11 (t, JZ9.6 Hz,
1H), 5.05 (dd, JZ8.1, 9.6 Hz, 1H), 4.61 (d, JZ8.1 Hz, 1H),
4.49 (ddd, JZ1.5, 5.5, 13.1 Hz, 1H), 4.29–4.23 (m, 2H),
4.16 (dd, JZ2.0, 12.6 Hz, 1H), 3.71 (ddd, JZ2.0, 4.6,
9.6 Hz, 1H), 2.08 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 2.01 (s,
3H); 13C NMR (CDCl3, 100 MHz) d: 170.6, 170.3, 169.4,
169.3, 134.9, 133.1, 131.6, 128.8, 127.7, 125.2, 99.7, 72.8,
71.8, 71.3, 69.7, 68.4, 61.9, 20.70, 20.59, 20.57. Anal.
Found: C, 55.08; H, 5.43%. Calcd for C23H27ClO10: C,
55.37; H, 5.25%, Cl, 7.11%.
5.3.6. 3-Methoxycinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4f). Obtained in 86% yield as a white
solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4f in 54% yield, a pure white powder to be
analyzed by microanalyses. Mp: 102.0–103.5 8C; [a]D27
K31.1 (c 0.50, MeOH); IR (KBr) 1743, 1600, 1439,
1
1369, 1325, 1227, 1169, 1040, 986, 913 cmK1; H NMR
(CDCl3, 400 MHz) d: 7.22 (dd, JZ7.6, 8.1 Hz, 1H), 6.96 (d,
JZ7.6 Hz, 1H), 6.92 (d, JZ2.5 Hz, 1H), 6.81 (dd, JZ2.5,
8.1 Hz, 1H), 6.56 (d, JZ15.6 Hz, 1H), 6.21 (td, JZ6.5,
15.6 Hz, 1H), 5.21 (t, JZ9.6 Hz, 1H), 5.11 (t, JZ9.6 Hz,
1H), 5.05 (dd, JZ7.6, 9.6 Hz, 1H), 4.62 (d, JZ7.6 Hz, 1H),
4.49 (ddd, JZ1.5, 5.6, 13.1 Hz, 1H), 4.31–4.24 (m, 2H),
4.16 (dd, JZ2.5, 12.1 Hz, 1H), 3.82 (s, 3H), 3.71 (ddd, JZ
2.5, 5.0, 9.6 Hz, 1H), 2.09 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H),
2.01 (s, 3H); 13C NMR (CDCl3, 100 MHz) d: 170.7, 170.2,
169.4, 169.3, 159.8, 137.8, 132.9, 129.6, 124.8, 119.1,
113.5, 111.9, 99.6, 72.9, 71.8, 71.3, 69.8, 68.4, 61.9, 55.2,
20.69, 20.58, 20.56. Anal. Found: C, 58.23; H, 6.09%. Calcd
for C24H30O11: C, 58.29; H, 6.12%.
5.3.10. 4-Cyanocinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4j). Obtained in 75% yield as a white
solid. The white solid was recrystallized from ether/
n-hexane to get 4j in 51% yield, a pure white solid. Mp:

M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
10565
135.5–137.0 8C; [a]D30 K29.3 (c 0.29, CHCl3); IR (KBr)
2226, 1745, 1604, 1381, 1227, 1038, 977, 906, 850 cmK1
7.42 (m, 2H), 6.76 (d, JZ16.1 Hz, 1H), 6.34 (ddd, JZ5.6,
6.6, 15.6 Hz, 1H), 5.23 (t, JZ9.6 Hz, 1H), 5.12 (t, JZ
9.6 Hz, 1H), 5.07 (dd, JZ8.1, 9.6 Hz, 1H), 4.66 (d, JZ
8.1 Hz, 1H), 4.55 (ddd, JZ1.5, 5.6, 13.1 Hz, 1H), 4.34 (ddd,
JZ1.5, 6.5, 13.1 Hz, 1H), 4.28 (dd, JZ4.5, 12.1 Hz, 1H),
4.17 (dd, JZ2.5, 12.1 Hz, 1H), 3.72 (ddd, JZ2.5, 4.5,
9.6 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 2.01 (s,
3H); 13C NMR (CDCl3, 100 MHz) d: 170.7, 170.3, 169.38,
169.35, 133.8, 133.5, 133.14, 133.11, 128.3, 128.0, 127.7,
126.6, 126.3, 126.0, 124.8, 123.4, 99.7, 72.9, 71.8, 71.4,
70.0, 68.4, 61.9, 20.7, 20.60, 20.57; HR-MS (FAB-MS) m/z:
515.1920 (MC1)C; Calcd for C27H30O10 m/z: 515.1918
(MC1)C.
;
1H NMR (CDCl3, 400 MHz) d: 7.61 (d, JZ8.6 Hz, 2H),
7.45 (d, JZ8.6 Hz, 2H), 6.61 (d, JZ16.1 Hz, 1H), 6.35
(ddd, JZ5.0, 6.0, 16.1 Hz, 1H), 5.23 (t, JZ9.6 Hz, 1H),
5.12 (t, JZ9.6 Hz, 1H), 5.06 (dd, JZ8.3, 9.6 Hz, 1H), 4.61
(d, JZ8.3 Hz, 1H), 4.54 (ddd, JZ1.5, 5.0, 13.6 Hz, 1H),
4.30 (ddd, JZ1.5, 6.0, 13.6 Hz, 1H), 4.27 (dd, JZ4.6,
12.1 Hz, 1H), 4.17 (dd, JZ2.5, 12.1 Hz, 1H), 3.72 (ddd, JZ
2.5, 4.6, 9.6 Hz, 1H), 2.08 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H),
2.01 (s, 3H); 13C NMR (CDCl3, 100 MHz) d: 170.6, 170.2,
169.4, 169.3, 140.9, 132.4, 130.4, 129.7, 126.9, 118.8,
111.1, 100.0, 72.7, 71.9, 71.3, 69.2, 68.3, 61.8, 20.7, 20.56,
20.54; HR-MS (FAB-MS) m/z: 490.1718 (MC1)C; Calcd
for C24H27NO10 m/z: 490.1713 (MC1)C.
5.3.14. Cinnamyl b-D-glucopyranoside (Rosin) (1a).
Compound 4a (0.10 g, 0.22 mmol) was dissolved in 2 mL
of methanol and 25% NaOMe in MeOH (0.14 g,
0.66 mmol) was added. The solution was stirred for
30 min. A small amount of ion exchange resin (Amberlyst
15, HC-form) was added to remove sodium ions. The
reaction mixture was diluted with methanol and resin was
filtered off and washed thoroughly. The filtrate was
evaporated to dryness to give 1a (0.061 g, 95%) as a
colorless amorphous. [a]2D7 K52.4 (c 0.49, MeOH) {lit.3a,b
[a]2D0 K44.8 (c 2.8, CHCl3–MeOH [1/1])}; IR (KBr) 3398,
1652, 1564, 1075 cmK1; 1H NMR (methanol-d4, 400 MHz)
d: 7.43–7.40 (m, 2H), 7.32–7.27 (m, 2H), 7.23–7.19 (m,
1H), 6.68 (d, JZ15.6 Hz, 1H), 6.37 (dt, JZ15.6, 6.0 Hz,
1H), 4.53 (ddd, JZ1.5, 6.0, 12.6 Hz, 1H), 4.36 (d, JZ
7.6 Hz, 1H), 4.32 (ddd, JZ1.5, 6.5, 12.6 Hz, 1H), 3.88 (dd,
JZ5.0, 11.6 Hz, 1H), 3.70–3.65 (m, 1H), 3.38–3.20 (m,
4H); 1H NMR (acetone-d6, 400 MHz) d: 7.34–7.31 (m, 2H),
7.22–7.18 (m, 2H), 7.13–7.09 (m, 1H), 6.57 (d, JZ15.9 Hz,
1H), 6.24 (dt, JZ6.1, 15.9 Hz, 1H), 4.36 (ddd, JZ1.5, 5.6,
13.1 Hz, 1H), 4.26 (d, JZ7.8 Hz, 1H), 4.13 (ddd, JZ1.5,
6.3, 13.1 Hz, 1H), 3.72 (dd, JZ2.5, 11.6 Hz, 1H), 3.54 (dd,
JZ5.6, 11.6 Hz, 1H), 3.33–3.10 (m, 4H); 13C NMR
(methanol-d4, 100 MHz) d: 138.0, 133.5, 129.3, 128.4,
127.3, 126.5, 103.1, 77.9, 77.8, 74.9, 71.5, 70.6, 62.6; HR-
MS (FAB-MS) m/z: 297.1333; Calcd for C15H20O6 m/z:
297.1338 (MC1)C.
5.3.11. 4-(Trifluoromethyl)cinnamyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (4k). Obtained in 45% yield
as a colorless prism. Mp: 98.0–98.6 8C; [a]3D0 K26.7 (c 0.29,
CHCl3); IR (KBr) 1753, 1374, 1330, 1222, 1165, 1120,
1
1041 cmK1; H NMR (CDCl3, 400 MHz) d: 7.58 (d, JZ
8.1 Hz, 2H), 7.46 (d, JZ8.1 Hz, 2H), 6.63 (d, JZ16.1 Hz,
1H), 6.32 (td, JZ5.6, 15.6 Hz, 1H), 5.23 (t, JZ9.6 Hz, 1H),
5.12 (t, JZ9.6 Hz, 1H), 5.06 (dd, JZ7.6, 9.6 Hz, 1H), 4.62
(d, JZ7.6 Hz, 1H), 4.53 (ddd, JZ1.5, 5.6, 13.6 Hz, 1H),
4.33–4.25 (m, 2H), 4.17 (dd, JZ2.5, 12.1 Hz, 1H), 3.72
(ddd, JZ2.5, 4.5, 9.6 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 3H),
2.03 (s, 3H), 2.02 (s, 3H); 13C NMR (CDCl3, 100 MHz) d:
170.6, 170.2, 169.34, 169.26, 139.9, 131.0, 129.6 (q, JC–F
Z
32 Hz), 127.4, 126.6, 125.5 (q, JC–FZ3.7 Hz), 124.1 (q, JC–
FZ270 Hz), 99.9, 72.8, 71.9, 71.3, 69.4, 68.3, 61.9, 20.7,
20.54, 20.52. Anal. Found: C, 54.04; H, 5.26%. Calcd for
C24H27F3O10: C, 54.14; H, 5.11%.
5.3.12. 3-Nitrocinnamyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (4l). Obtained in 63% yield as a white
solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4l in 55% yield, a pure white powder to be
analyzed by microanalyses. Mp: 150.7–151.3 8C; [a]D30
K28.6 (c 0.39, CHCl3); IR (KBr) 1755, 1530, 1349, 1216,
1163, 1038, 815, 736, 684 cmK1 1H NMR (CDCl3,
;
400 MHz) d: 8.23–8.22 (m, 1H), 8.12–8.09 (m, 1H), 7.67
(d, JZ8.1 Hz, 1H), 7.50 (t, JZ8.1 Hz, 1H), 6.66 (d, JZ
16.1 Hz, 1H), 6.37 (td, JZ5.6, 15.6 Hz, 1H), 5.23 (t, JZ
9.6 Hz, 1H), 5.12 (t, JZ9.6 Hz, 1H), 5.07 (dd, JZ7.6,
9.6 Hz, 1H), 4.63 (d, JZ7.6 Hz, 1H), 4.55 (ddd, JZ1.5, 5.6,
13.6 Hz, 1H), 4.31 (ddd, JZ1.5, 6.0, 13.6 Hz, 1H), 4.28 (dd,
JZ4.5, 12.1 Hz, 1H), 4.17 (dd, JZ2.5, 12.1 Hz, 1H), 3.72
(ddd, JZ2.5, 4.5, 9.6 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H),
2.03 (s, 3H), 2.02 (s, 3H); 13C NMR (CDCl3, 100 MHz) d:
170.6, 170.2, 169.33, 169.25, 148.6, 138.2, 132.3, 129.9,
129.5, 128.0, 122.3, 121.0, 99.9, 72.7, 71.9, 71.2, 69.2, 68.3,
61.8, 20.7, 20.54, 20.52. Anal. Found: C, 54.24; H, 5.32; N,
2.75%. Calcd for C24H27F3O10: C, 54.14; H, 5.11; N, 2.79%.
5.3.15. 4-Hydroxycinnamyl b-D-glucopyranoside
(Sachaliside 1, Triandirin) (1b). Compound 4b (0.10 g,
0.21 mmol) was dissolved in 2 mL of methanol and 25%
NaOMe in MeOH (0.14 g, 0.66 mmol) was added. The
solution was stirred for 30 min. A small amount of ion
exchange resin (Amberlyst 15, HC-form) was added to
remove sodium ions. The reaction mixture was diluted with
methanol and resin was filtered off and washed thoroughly.
The filtrate was evaporated to dryness to give 1b (0.062 g,
95%) as a colorless amorphous. [a]2D2 K62.2 (c 0.60,
MeOH) {lit.4e [a]D20 K62.3 (H2O)}; IR (KBr) 3299, 2929,
1
1609, 1515, 1443, 1375, 1249, 1170, 1083, 841 cmK1; H
NMR (pyridine-d5, 400 MHz) d: 7.40 (d, JZ8.6 Hz, 2H),
7.15 (d, JZ8.6 Hz, 2H), 6.73 (d, JZ15.6 Hz, 1H), 6.36 (dt,
JZ6.0, 15.6 Hz, 1H), 4.99 (d, JZ7.6 Hz, 2H), 4.75 (dd, JZ
6.0, 12.6 Hz, 1H), 4.58 (dd, JZ1.5, 11.6 Hz, 1H), 4.47 (dd,
JZ6.0, 12.6 Hz, 1H), 4.41 (dd, JZ5.0, 11.6 Hz, 1H), 4.32–
4.24 (m, 2H), 4.14–4.08 (m, 1H), 4.00–3.94 (m, 1H); 13C
NMR (pyridine-d5, 100 MHz) d: 158.9, 132.6, 128.6, 128.4,
116.5, 103.9, 78.59, 78.55, 75.3, 71.7, 70.1, 62.8; 13C NMR
(DMSO-d6, 100 MHz) d: 157.1, 131.7, 127.6, 127.5, 122.6,
5.3.13. Naphthalene-2-ylalloxy 2,3,4,6-tetra-O-acethyl-
b-D-glucopyranoside (4m). Obtained in 53% yield as a
white solid. The white solid was recrystallized from AcOEt/
n-hexane to give 4m in 43% yield, a pure white solid to be
analyzed by microanalyses. Mp: 147.5–149.2 8C; [a]D31
K29.4 (c 0.38, CHCl3); IR (KBr) 1748, 1369, 1225, 1167,
1128, 1050 cmK1; 1H NMR (CDCl3, 00 MHz) d: 7.80–7.78
(m, 3H), 7.73 (1H, s), 7.58 (dd, JZ1.5, 8.6 Hz, 1H), 7.49–

10566
M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
115.4, 102.0, 76.9, 76.8, 73.5, 70.1, 68.8, 61.1; HR-MS
(FAB-MS) m/z: 313.1288 (MC1)C; Calcd for C15H20O7
m/z: 313.1287 (MC1)C.
12.6 Hz, 1H), 3.78 (dd, JZ2.0, 12.1 Hz, 1H), 3.74 (s, 6H),
3.62 (s, 3H), 3.68 (dd, JZ5.0, 12.1 Hz, 1H), 3.28–3.12 (m,
4H); 1H NMR (pyridine-d5, 400 MHz) d: 6.76 (s, 2H), 6.75
(d, JZ15.6 Hz, 1H), 6.46 (dt, JZ6.0, 15.6 Hz, 1H), 4.99 (d,
JZ8.0 Hz, 1H), 4.78 (ddd, JZ1.5, 5.6, 12.6 Hz, 1H), 4.57
(dd, JZ2.5, 12.1 Hz, 1H), 4.51 (dd, JZ6.0, 12.6 Hz, 1H),
4.39 (dd, JZ5.5, 11.6 Hz, 1H), 4.29–4.23 (m, 2H), 4.14–
4.10 (m, 1H), 4.00–3.95 (m, 1H), 3.87 (s, 3H), 3.74 (s, 6H);
13C NMR (methanol-d4, 100 MHz) d: 154.4, 138.7, 134.2,
133.4, 126.1, 104.7, 103.2, 77.9, 77.8, 74.9, 71.5, 70.5, 62.6,
60.9, 56.4; 13C NMR (pyridine-d5, 100 MHz) d: 154.0,
138.7, 133.2, 132.2, 126.2, 104.4, 104.0, 78.6, 75.3, 71.7,
69.7, 62.8, 60.6, 56.0; HR-MS (FAB-MS) m/z: 387.1620
(MC1)C; Calcd for C18H26O9 m/z: 387.1655 (MC1)C.
5.3.16. 4-Methoxycinnamyl b-D-glucopyranoside
(Vimalin) (1c). A mixture of 4c (0.055 g, 0.11 mmol) and
K2CO3 (0.15 g, 1.1 mmol) in MeOH (1.1 mL) was stirred
for 30 min at room temperature. The reaction mixture was
evaporated to dryness and the residue was purified by flash
column chromatography on silica gel (CH2Cl2/MeOH as an
eluent) to afford 1c (0.025 g, 69%) as a white solid. Mp:
111.0–112.5 8C; [a]2D2 K54.7 (c 1.40, MeOH){lit.4b,c [a]D20
K60.6 (MeOH)}; IR (KBr) 3350, 2938, 1605, 1514, 1368,
1245, 1169, 1083, 1022, 968, 781 cmK1 1H NMR
;
(pyridine-d5, 400 MHz) d: 7.38 (d, JZ8.6 Hz, 1H), 6.95
(d, JZ8.6 Hz, 1H), 6.74 (d, JZ16.1 Hz, 1H), 6.38 (dt, JZ
16.1, 6.0 Hz, 1H), 4.99 (d, JZ8.0 Hz, 1H), 4.76 (ddd, JZ
1.5, 5.6, 12.6 Hz, 1H), 4.59 (dd, JZ2.0, 11.6 Hz, 1H), 4.50–
4.41 (m, 2H), 4.32–4.25 (m, 2H), 4.15–4.11 (m, 1H), 4.02–
3.95 (m, 1H), 3.66 (s, 3H); 13C NMR (pyridine-d5,
100 MHz) d: 159.9, 132.1, 130.2, 128.2, 124.6, 114.6,
104.1, 78.8, 78.7, 75.4, 71.8, 70.1, 62.9, 55.3; HR-MS
(FAB-MS) m/z: 327.1417 (MC1)C; Calcd for C16H22O7
m/z: 327.1444 (MC1)C.
5.3.19. 3-Methoxycinnamyl b-D-glucopyranoside (1f). A
mixture of 4f (0.23 g, 0.46 mmol) and K2CO3 (0.64 g,
4.6 mmol) in MeOH (4.6 mL) was stirred for 30 min at
room temperature. The reaction mixture was evaporated to
dryness and the residue was purified by flash column
chromatography on silica gel (CH2Cl2/MeOH as an eluent)
to afford 1f (0.12 g, 79%) as a colorless solid. Mp: 85.0–
86.0 8C; [a]2D2 K40.9 (c 0.77, MeOH); IR (KBr) 3370, 2925,
1603, 1581, 1489, 1432, 1366, 1255, 1159, 1078, 1046, 765,
1
685, 632 cmK1; H NMR (methanol-d4, 400 MHz) d: 7.21
(t, JZ8.1 Hz, 1H), 6.99 (d, JZ8.1 Hz, 1H), 6.96 (d, JZ
2.0 Hz, 1H), 6.80 (dd, JZ2.0, 8.1 Hz, 1H), 6.65 (d, JZ
16.1 Hz, 1H), 6.36 (dt, JZ16.1, 6.0 Hz, 1H), 4.52 (ddd,
JZ1.5, 6.0, 12.6 Hz, 1H), 4.37 (d, JZ7.6 Hz, 1H), 4.32
(ddd, JZ1.0, 6.5, 12.6 Hz, 1H), 3.89 (dd, JZ1.5, 12.1 Hz,
1H), 3.78 (s, 3H), 3.69 (dd, JZ5.6, 12.1 Hz, 1H), 3.38–3.20
(m, 4H); 13C NMR (methanol-d4, 100 MHz) d: 161.3, 139.6,
133.6, 130.5, 127.0, 120.1, 114.3, 112.8, 103.3, 78.1, 77.9,
75.1, 71.6, 70.7, 62.8, 55.6; HR-MS (FAB-MS) m/z:
349.1270 (MCNa)C; Calcd for C16H22O7 m/z: 349.1263
(MCNa)C.
5.3.17. 4-Hydroxy-3-methoxycinnamyl b-D-gluco-
pyranoside (Citrusin D, Coniferin) (1d). Compound 4d
(0.051 g, 0.10 mmol) was dissolved in 1 mL of methanol
and 25% NaOMe in MeOH (0.020 g, 0.10 mmol) was
added. The solution was stirred for 1 h. A small amount of
ion exchange resin (Amberlyst 15, HC-form) was added to
remove sodium ions. The reaction mixture was diluted with
methanol and resin was filtered off and washed thoroughly.
The filtrate was evaporated to dryness under 5 8C to give 1e
(0.034 g, 99%) as a pale yellow amorphous. [a]2D3 K36.0 (c
0.54, MeOH); IR (KBr) 3382, 2862, 1515, 1278, 1032 cmK1
;
1H NMR (methanol-d4, 400 MHz) d: 7.01 (d, JZ2.0 Hz,
1H), 6.85 (dd, JZ2.0, 8.1 Hz, 1H), 6.73 (d, JZ8.1 Hz, 1H),
6.57 (d, JZ16.1 Hz, 1H), 6.19 (td, JZ6.0, 16.1 Hz, 1H),
4.49 (ddd, JZ1.5, 5.6, 12.6 Hz, 1H), 4.36 (d, JZ8.0 Hz,
1H), 4.29 (ddd, JZ2.0, 6.5, 12.6 Hz, 1H), 3.90–3.82 (m,
1H), 3.86 (s, 3H), 3.68 (dd, JZ5.0, 12.1 Hz, 1H), 3.38–3.20
(m, 4H); 13C NMR (methanol-d4, 100 MHz) d: 149.1, 147.7,
134.3, 130.4, 123.7, 121.2, 116.2, 110.6, 103.2, 78.1, 78.0,
75.1, 71.7, 71.0, 62.8, 56.4; HR-MS (FAB-MS) m/z:
343.1365 (MC1)C; Calcd for C18H26O9 m/z: 343.1393
(MC1)C.
5.3.20. 2-Methoxycinnamyl b-D-glucopyranoside (1g).
Compound 4g (0.20 g, 0.40 mmol) was dissolved in 4 mL
of methanol and 25% NaOMe in MeOH (0.26 g, 1.2 mmol)
was added. The solution was stirred for 30 min. A small
amount of ion exchange resin (Amberlyst 15, HC-form) was
added to remove sodium ions. The reaction mixture was
diluted with methanol and resin was filtered off and washed
thoroughly. The filtrate was evaporated to dryness to give 1g
(0.11 g, 82%) as a colorless amorphous. [a]2D7 K36.7 (c
1.03, MeOH); IR (KBr) 3386, 2926, 1575, 1490, 1462,
1
1245, 1024, 754 cmK1; H NMR (methanol-d4, 400 MHz)
d: 7.45 (dd, JZ1.5, 7.6 Hz, 1H), 7.21 (ddd, JZ1.5, 7.6,
7.6 Hz, 1H), 6.97–6.87 (m, 3H), 6.35 (dt, JZ16.1, 6.0 Hz,
1H), 4.52 (ddd, JZ1.5, 6.0, 12.6 Hz, 1H), 4.37 (d, JZ
7.6 Hz, 1H), 4.31 (ddd, JZ1.5, 6.5, 12.6 Hz, 1H), 3.87 (dd,
JZ2.0, 12.1 Hz, 1H), 3.83 (s, 3H), 3.68 (dd, JZ5.0,
12.1 Hz, 1H), 3.38–3.20 (m, 4H); 13C NMR (methanol-d4,
100 MHz) d: 158.0, 129.8, 128.8, 127.7, 126.8, 126.7,
121.5, 111.8, 103.1, 77.9, 77.8, 74.9, 71.4, 70.2, 62.6, 55.4;
HR-MS (FAB-MS) m/z: 327.1447 (MC1)C; Calcd for
C16H22O7 m/z: 327.1444 (MC1)C.
5.3.18. 3,4,5-Trimethoxycinnamyl b-D-glucopyranoside
(Icariside H1) (1e). Compound 4e (0.055 g, 0.10 mmol)
was dissolved in 1 mL of methanol and 25% NaOMe in
MeOH (0.020 g, 0.10 mmol) was added. The solution was
stirred for 1 h. A small amount of ion exchange resin
(Amberlyst 15, HC-form) was added to remove sodium
ions. The reaction mixture was diluted with methanol and
resin was filtered off and washed thoroughly. The filtrate
was evaporated to dryness to give 1e (0.038 g, 99%) as a
colorless amorphous. [a]2D6 K42.2 (c 0.24, MeOH){lit.6a
[a]2D3 K47.6 (c 0.62, MeOH)}; IR (KBr) 3398, 1583, 1507,
1
1460, 1419, 1336, 1243, 1125 cmK1; H NMR (methanol-
5.3.21. 3,4-Dimethoxycinnamyl b-D-glucopyranoside
(1h). A mixture of 4h (0.059 g, 0.11 mmol) and K2CO3
(0.15 g, 1.1 mmol) in MeOH (1.1 mL) was stirred for
30 min at room temperature. The reaction mixture was
d4, 400 MHz) d: 6.63 (s, 2H), 6.52 (d, JZ16.1 Hz, 1H), 6.21
(dt, JZ6.0, 16.1 Hz, 1H), 4.41 (ddd, JZ1.5, 5.6, 12.6 Hz,
1H), 4.27 (d, JZ7.5 Hz, 1H), 4.22 (ddd, JZ2.0, 6.5,

M. Kishida, H. Akita / Tetrahedron 61 (2005) 10559–10568
10567
evaporated to dryness and the residue was purified by flash
column chromatography on silica gel (CH2Cl2/MeOH as an
eluent) to afford 1h (0.024 g, 60%) as a colorless
amorphous. [a]2D7 K30.2 (c 1.08, MeOH); IR (KBr) 3391,
1515, 1461, 1264, 1024, 621 cmK1; 1H NMR (methanol-d4,
400 MHz) d: 6.95 (d, JZ1.5 Hz, 1H), 6.85 (dd, JZ1.5,
8.6 Hz, 1H), 6.79 (d, JZ8.6 Hz, 1H), 6.50 (d, JZ16.1 Hz,
1H), 6.15 (dt, JZ16.1, 6.0 Hz, 1H), 4.40 (ddd, JZ1.5, 5.6,
12.6 Hz, 1H), 4.27 (d, JZ7.5 Hz, 1H), 4.21 (dd, JZ7.0,
12.6 Hz, 1H), 3.78 (dd, JZ2.0, 12.1 Hz, 1H), 3.74 (s, 3H),
3.72 (s, 3H), 3.58 (dd, JZ5.0, 12.1 Hz, 1H), 3.28–3.10 (m,
4H); 13C NMR (methanol-d4, 100 MHz) d: 150.3, 150.2,
133.6, 131.4, 124.5, 120.8, 112.6, 110.5, 103.0, 77.9, 77.8,
74.9, 71.5, 70.7, 62.6, 56.3, 56.2; HR-MS (FAB-MS) m/z:
357.1519 (MC1)C; Calcd for C17H24O8 m/z: 357.1549
(MC1)C.
column chromatography on silica gel (CH2Cl2/MeOH as an
eluent) to afford 1k (0.077 g, 63%) as a white solid. Mp:
142.5–144.5 8C; [a]2D7 K39.8 (c 0.41, MeOH); IR (KBr)
3362, 2931, 1418, 1328, 1171, 1110, 1070, 1041, 849,
1
639 cmK1; H NMR (methanol-d4, 400 MHz) d: 7.60 (s,
4H), 6.78 (d, JZ16.1 Hz, 1H), 6.56 (dt, JZ16.1, 6.0 Hz,
1H), 4.56 (ddd, JZ1.5, 5.5, 13.6 Hz, 1H), 4.39–4.33 (m,
2H), 3.88 (dd, JZ2.0, 11.6 Hz, 1H), 3.70–3.65 (m, 1H),
3.39–3.22 (m, 4H); 13C NMR (methanol-d4, 100 MHz) d:
142.2, 131.8, 130.3 (q, JC–FZ27 Hz), 130.1, 127.9, 126.5,
125.7 (q, JC–FZ269 Hz), 103.6, 78.1, 78.0, 75.1, 71.7, 70.3,
62.8; HR-MS (FAB-MS) m/z: 365.1216 (MC1)C; Calcd
for C16H19NO6 m/z: 365.1212 (MC1)C.
5.3.25. 3-Nitrocinnamyl b-D-glucopyranoside (1l). A
mixture of 4l (0.14 g, 0.27 mmol) and K2CO3 (0.38 g,
2.7 mmol) in MeOH–THF (4 mL, 1/1, v/v) was stirred for
30 min at room temperature. The reaction mixture was
evaporated to dryness and the residue was purified by flash
column chromatography on silica gel (CH2Cl2/MeOH as an
eluent) to afford 1l (0.082 g, 87%) as a white solid. Mp:
139.2–140.7 8C; [a]2D2 K40.3 (c 0.52, MeOH); IR (KBr)
3370, 2926, 2500, 1527, 1347, 1169, 1077, 1041, 729, 668,
630 cmK1; 1H NMR (methanol-d4, 400 MHz) d: 8.28 (t, JZ
2.0 Hz, 1H), 8.12–8.07 (m, 1H), 7.83 (d, JZ8.0 Hz, 1H),
7.56 (t, JZ8.0 Hz, 1H), 7.83 (d, JZ15.6 Hz, 1H), 6.57 (dt,
JZ15.6, 5.6 Hz, 1H), 4.57 (ddd, JZ1.5, 5.0, 13.6 Hz, 1H),
4.40–4.33 (m, 2H), 3.88 (d, JZ11.6 Hz, 1H), 3.70–3.65 (m,
1H), 3.39–3.22 (m, 4H); 13C NMR (methanol-d4, 100 MHz)
d: 150.0, 140.3, 133.4, 130.8, 130.6, 130.5, 123.0, 121.9,
103.6, 78.1, 78.0, 75.1, 71.7, 70.2, 62.8; HR-MS (FAB-MS)
m/z: 342.1176 (MC1)C; Calcd for C15H19NO8 m/z:
342.1189 (MC1)C.
5.3.22. 4-Chlorocinnamyl b-D-glucopyranoside (1i).
Compound 4i (0.20 g, 0.40 mmol) was dissolved in 4 mL
of methanol and 25% NaOMe in MeOH (0.26 g, 1.2 mmol)
was added. The solution was stirred for 30 min. A small
amount of ion exchange resin (Amberlyst 15, HC-form) was
added to remove sodium ions. The reaction mixture was
diluted with methanol and resin was filtered off and washed
thoroughly. The filtrate was evaporated to dryness to give 1i
(0.13 g, 85%) as a white solid. Mp: 160.2–161.5 8C; [a]D27
K48.5 (c 0.55, MeOH); IR (KBr) 3314, 2870, 2371, 1746,
1
1491, 1363, 1229, 1170, 1091, 1041, 976 cmK1; H NMR
(methanol-d4, 400 MHz) d: 7.40 (d, JZ8.6 Hz, 2H), 7.30 (d,
JZ8.6 Hz, 2H), 6.67 (d, JZ15.6 Hz, 1H), 6.38 (dt, JZ15.6,
6.0 Hz, 1H), 4.52 (ddd, JZ1.5, 6.0, 12.6 Hz, 1H), 4.35 (d,
JZ7.6 Hz, 1H), 4.32 (ddd, JZ1.5, 6.5, 12.6 Hz, 1H), 3.90–
3.86 (m, 1H), 3.70–3.65 (m, 1H), 3.38–3.20 (m, 4H); 13C
NMR (methanol-d4, 100 MHz) d: 136.8, 134.0, 131.9,
129.4, 128.7, 127.6, 103.2, 77.9, 77.8, 74.9, 71.5, 70.3, 62.6;
HR-MS (FAB-MS) m/z: 331.0944 (MC1)C; Calcd for
C15H19ClO6 m/z: 331.0948 (MC1)C.
5.3.26. 3-Naphthalene-2-ylalloxy b-D-glucopyranoside
(1m). A mixture of 4m (0.18 g, 0.35 mmol) and K2CO3
(0.49 g, 3.5 mmol) in MeOH–THF (4 mL, 1/1, v/v) was
stirred for 30 min at room temperature. The reaction
mixture was evaporated to dryness and the residue was
purified by flash column chromatography on silica gel
(CH2Cl2/MeOH as an eluent) to afford 1m (0.090 g, 73%) as
a white solid. Mp: 161.0–163.0 8C; [a]2D2 K46.8 (c 0.36,
MeOH); IR (KBr) 3518, 3339, 2931, 2871, 1153, 1037, 967,
5.3.23. 4-Cyanocinnamyl b-D-glucopyranoside (1j). Com-
pound 4j (0.50 g, 0.10 mmol) was dissolved in 2 mL of
methanol and 25% NaOMe in MeOH (0.024 g, 0.11 mmol)
was added. The solution was stirred for 30 min. A small
amount of ion exchange resin (Amberlyst 15, HC-form) was
added to remove sodium ions. The reaction mixture was
diluted with methanol and resin was filtered off and washed
thoroughly. The filtrate was evaporated to dryness to give 1j
(0.033 g, 100%) as a white solid. Mp: 131.0–133.0 8C; [a]D27
K35.1 (c 0.70, MeOH); IR (KBr) 3398, 2927, 2225, 1723,
896, 798, 744, 618, 480 cmK1 1H NMR (methanol-d4,
;
400 MHz) d: 7.60–7.55 (m, 4H), 7.44 (dd, JZ2.0, 8.5 Hz,
1H), 7.24–7.20 (m, 2H), 6.64 (d, JZ16.1 Hz, 1H), 6.29 (dt,
JZ6.0, 16.1 Hz, 1H), 4.37 (ddd, JZ1.5, 6.0, 12.6 Hz, 1H),
4.18 (d, JZ7.6 Hz, 1H), 4.17 (ddd, JZ1.5, 6.6, 12.6 Hz,
1H), 3.67 (dd, JZ2.0, 11.6 Hz, 1H), 3.50–3.44 (m, 1H),
3.39–3.22 (m, 4H); 13C NMR (methanol-d4, 100 MHz) d:
135.7, 135.1, 134.5, 133.7, 129.2, 129.0, 128.6, 127.5,
127.2, 126.8, 124.6, 124.5, 103.4, 78.1, 78.0, 75.1, 71.7,
70.8, 62.8.; HR-MS (FAB-MS) m/z: 369.1318 (MCNa)C;
Calcd for C19H22O6 m/z: 369.1314 (MCNa)C.
1
1604, 1367, 1285, 1170, 1076, 850, 550 cmK1; H NMR
(methanol-d4, 400 MHz) d: 7.66 (d, JZ7.6 Hz, 2H), 7.58 (d,
JZ7.6 Hz, 2H), 6.77 (d, JZ16.1 Hz, 1H), 6.56 (dt, JZ16.1,
6.0 Hz, 1H), 4.57 (dd, JZ5.0, 12.6 Hz, 1H), 4.38–4.33 (m,
2H), 3.88 (d, JZ11.6 Hz, 1H), 3.70–3.65 (m, 1H), 3.39–
3.22 (m, 4H); 13C NMR (methanol-d4, 100 MHz) d: 142.9,
133.3, 131.2, 131.0, 128.0, 119.6, 111.5, 103.4, 77.9, 77.8,
74.9, 71.5, 70.0, 62.6; HR-MS (FAB-MS) m/z: 322.1283
(MC1)C; Calcd for C16H19NO6 m/z: 322.1291 (MC1)C.
References and notes
5.3.24. 4-(Trifluoromethyl)cinnamyl b-D-glucopyrano-
side (1k). A mixture of 4k (0.18 g, 0.34 mmol) and
K2CO3 (0.47 g, 3.4 mmol) in MeOH (1.7 mL) was stirred
for 2 h at room temperature. The reaction mixture was
evaporated to dryness and the residue was purified by flash
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