Synthesis of benzyl tetra-O-acetyl-α-L-glucopyranoside from benzyl 2,3-dideoxy-β-D-Erythro-hex-2-enopyranoside

Article abstract of DOI:10.3987/COM-16-S(S)54

Benzyl tetra-O-acetyl-α-L-glucopyranoside was synthesized from benzyl 2,3-dideoxy-β-D-erythro-hex-2-enopyranoside in six steps and 19% overall yield. Epoxidation from the β-side of the double bond between C-2 and C-3 of the starting material along with the subsequent regioselective ring opening by the backside attack of a hydroxide ion at C-3 furnished an intermediate with D-ido-stereochemistry. The inversion at C-5 was performed by an epimerization, by way of an N-cyclohexylenamine, after the chemoselective oxidation at primary hydroxy group of the C-6 to an aldehyde. The present synthesis of L-glucose derivatives implies the sequential stereochemical inversion of C-2 to C-5 of D-glucose. As the present synthesis keeps the whole skeleton and the order of carbon atoms based on the original numbering of D-glucose, it would work well for the synthesis of specifically labeled derivatives, beginning from isotopically labeled D-glucoses.

Full text of DOI:10.3987/COM-16-S(S)54

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HETEROCYCLES, Vol. 95, No. 2, 2017
HETEROCYCLES, Vol. 95, No. 2, 2017, pp. 862-871. © 2017 The Japan Institute of Heterocyclic Chemistry
Received, 30th August, 2016, Accepted, 14th October, 2016, Published online, 22nd November, 2016
DOI: 10.3987/COM-16-S(S)54
SYNTHESIS
D-L-GLUCOPYRANOSIDE
ERYTHRO-HEX-2-ENOPYRANOSIDE
OF
BENZYL
TETRA-O-ACETYL-
2,3-DIDEOXY-E-D-
FROM BENZYL
Hayato Okazaki, Yuji Ueda, Kengo Hanaya, Mitsuru Shoji, and Takeshi
Sugai*
Department of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen,
Minato-ku, Tokyo 105-8512, Japan; E-mail: sugai-tk@pha.keio.ac.jp
Abstract – Benzyl tetra-O-acetyl-D-L-glucopyranoside was synthesized from
benzyl 2,3-dideoxy-E-D-erythro-hex-2-enopyranoside in six steps and 19%
overall yield. Epoxidation from the E-side of the double bond between C-2 and
C-3 of the starting material along with the subsequent regioselective ring opening
by the backside attack of a hydroxide ion at C-3 furnished an intermediate with
D-ido-stereochemistry. The inversion at C-5 was performed by an epimerization,
by way of an N-cyclohexylenamine, after the chemoselective oxidation at primary
hydroxy group of the C-6 to an aldehyde. The present synthesis of L-glucose
derivatives implies the sequential stereochemical inversion of C-2 to C-5 of
D-glucose. As the present synthesis keeps the whole skeleton and the order of
carbon atoms based on the original numbering of D-glucose, it would work well
for the synthesis of specifically labeled derivatives, beginning from isotopically
labeled D-glucoses.
INTRODUCTION
Many efforts have been devoted to the preparation of L-sugars from naturally abundant D-sugars, and
have ingeniously utilized the stereochemistry and the oxidation state of carbon atoms involved in the
starting material.1 Most of the previously reported examples to prepare L-glucose (1a) from D-glucose
(2a) added one carbon at C-1, and removed one carbon by cleaving the C−C bond between C-5 and C-6
(Scheme 1).2-9 In those examples, the original skeleton was inverted and C-1 to C-5 were regarded as
C-5 to C-1, respectively.

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863
Scheme 1. Previously reported important transformations to L-glucose (1a) from D-glucose (2a)
In contrast, Paulsen and co-workers attempted an entirely different approach, which was the simple
stereochemical inversion of C-2 to C-5 (Scheme 2). They treated penta-O-acetyl-D-glucose (2b) with
SbCl5, and they obtained the D-ido-configuration as the pentaacetyl form (3a) in one pot, with three
configurations at C-2 to C-4, which were inverted compared with that of the starting material.10
Scheme 2. Paulsen’s one-pot contiguous stereochemical inversion at C-2 to C-4 of D-glucose derivative
2b to D-idose derivative 3a
Crotti and co-workers reported an interesting variation11,12 of the Ferrier reaction13 of D-glucal derivatives
such as 4b, which can be prepared from 2b through several steps. The reaction accompanies the
inversion at C-4 with the concomitant introduction of a double bond between C-2 and C-3.
Scheme 3. Crotti’s Ferrier reaction of an epoxyglucal intermediate and our planned synthesis of
L-glucose derivative 1b from 5b

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The resulting product 5a can be submitted to vicinal dihydroxylation, to recover all functional groups in
the sugar. We envisioned that the introduction of oxygen atoms with the appropriate stereochemistry on
an analogous substance 5b and the inversion of the stereochemistry in C-5 at the later step, would enable
the transformation of 5b into L-glucose derivative 1b (Scheme 3).
RESULTS AND DISCUSSION
We independently developed a transformation similar to Crotti’s work (Scheme 4). D-Glucal (4a) was
regioselectively acetylated14 to 4c and the subsequent methylsulfonylation of the liberated hydroxy group
at C-4 furnished 4d in 89% yield. Our first attempt was the treatment of 4d with benzyl alcohol,
n-butyllithium and N,N,N,N-tetramethylethylenediamine, and 5b was obtained in 44% yield. All acetyl
groups were removed by the action of benzyl alkoxide under the reaction conditions. X-Ray
crystallographic analysis revealed exclusive E-orientation at the anomeric position,15 which indicated the
formation of an epoxide intermediate. As the product 5b gradually decomposed under the reaction
conditions, a higher yield could not be obtained by varying the reaction time and/or reaction temperature.
We were disappointed that with Crotti’s potassium tert-butoxide,11 the product was a 1:1 mixture of the
D- and E-anomers in yields as low as 10%.
Scheme 4. Short and stereoselective synthesis of 5b from 4a, via a Ferrier reaction of an epoxyglucal
intermediate
We thought both of the weakening the basicity of the reagents and Lewis acidity of metallic cation to be
important for the stability of the product. For the improvement of E-selectivity, a larger atomic radius of
metallic cation would be advantageous by allowing the coordination between oxygen atoms in the
epoxide and benzyl alcohol. For these reasons, we chose cesium carbonate as the next candidate. The
solvent was MeCN, in which the solubility of cesium carbonate is high. Under these conditions, the
reaction proceeded with good E-stereoselectivity and in higher yield (64%). In this case, a side product
1
(24%) was observed, whose dimeric structure (6) was suggested by its H-NMR and mass spectra.

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865
Finally, an increase in the number of equivalents of benzyl alcohol from 10 to 20 improved the yield
(81%) of 5b, which was isolated in a crystalline form, and side product formation was suppressed (11%)
(Scheme 4). Our presently developed route has two advantages, 1) ready accessibility of the reaction
substrate 4d from 4a, and 2) ease of isolation and high purity of product 5b owing to its crystalline
property.
Toward the synthesis of L-glucose, the addition of an oxygen atom at C-2 and C-3 was achieved by Payne
oxidation16 to give 7 in 80% yield. The next step was a regioselective ring opening reaction of the
E-oriented epoxide. Simple aqueous alkaline conditions at high temperature17 were effective, to furnish
3b in 81% yield. The stereochemistry of the product was confirmed by the coupling constants in the
1H-NMR data of the corresponding acetate 3c (Scheme 5), which indicated that the three acetoxy groups
each occupied an axial orientation. The nucleophilic attack of the hydroxide ion exclusively occurred at
C-3. The E-orientation of the substituent on the anomeric position was important for achieving such a
high regioselectivity. That is, when the stereochemistry at the anomeric position was reversed to be D,
which is predominant under conventional Ferrier conditions,13 we observed a lower preference for the
nucleophilic attack at C-3 in a structurally similar substrate.18
Scheme 5. Synthesis of D-idoside 3b from 5b, and the confirmation of the stereochemistry as 3c
The remaining task was the stereochemical inversion from the D-ido configuration to the L-gluco
configuration at C-5. Previously reported examples19,20 regarding π-facial selective hydroboration of
6-deoxy-hex-5-enopyranosides described the preferential formation of the D-ido-configuration over the
L-gluco-configuration. As an alternative, the epimerization at C-5 was realized by way of an aldehyde 8
(Scheme 6). The E-benzyloxy group at C-1 in the starting material would be effective in influencing the
equilibrium of epimerization. Such an anomeric alkoxy substituent occupies the thermodynamically
stable axial position and with the three hydroxy groups at C-2 to C-4, promotes the epimerization at the

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position adjacent to the aldehyde group, so that all substituents except for that at C-1 adopt the equatorial
position.
The transformation of 3b to L-gluco-1c was achieved in this way, although the yield was moderate (29%,
four steps from 3b). First, the primary hydroxy group at C-6 in 3b was selectively oxidized to aldehyde
8, by the action of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), trichloroisocyanuric acid (TCC), and
sodium hydrogen carbonate in N,N-dimethylformamide (DMF).21 The crude aldehyde was submitted to
the sequential three-step treatment as follows: 1) cyclohexylamine in CH2Cl2, 2) reduction of the crude
mixture including polar impurities with sodium borohydride in MeOH, and 3) acetylation of all resulting
hydroxy groups for the ease of purification of the product. The epimerization is presumed to occur by
way of the N-cyclohexylenamine 10 of the imines D-ido- and L-gluco-9. Note that the undesired isomer
D-ido-3b was not obtained at all. The stereochemistry of 1c was confirmed by the comparison of the
21
1
sign of the optical rotation [[D]D –135.6 (c 1.00, CHCl3)] and H-NMR spectrum with the antipodal
D-gluco isomer [lit.22 [D]D25 +144.1 (c 2.01, CHCl3)].
O
1)
2)
NaBH4
MeOH
3)
Ac2O
cyclohexyl-
amine
TEMPO
TCC
O
OBn
OAc
O
OBn
OH
AcO
pyridine
H
3b
AcO
HO
CH2Cl2
rt, 24 h
rt, 24 h
rt, 24 h
y: 29% from 3b
NaHCO3
DMF
OAc
OH
1c
D-ido-8
N-Cy
NH-Cy
O
N-Cy
O
OBn
OAc
O
OBn
OH
OBn
OH
O
OBn
OH
AcO
H
H
H
HO
HO
HO
OAc
OH
OH
10
OH
L-gluco-9
D-ido-9 Cy = cyclohexyl
11
OBn
OH
HO
OH
O
CHO
OHC
HO
O
HO
OH
OBn
O
HO
CHO
OH
OBn
L-gluco-8
OH
D-ido-8
Scheme 6. Inversion of the stereochemistry at C-5 by way of an aldehyde 8 to L-glucose derivative 1c
Before the above-mentioned result, several amines other than cyclohexylamine were examined. First,
the use of two secondary amines was attempted. With the use of piperidine, the formation of 11 could
not be avoided and the epimerization was slow, resulting in a mixture of L-gluco-1c (5%), D-ido-3c (5%),
and 11 (8%), after acetylation. Di-n-butylamine also furnished a complex mixture in lower yield. We
concluded that the increased basicity of secondary amines was deleterious, promoting the elimination of

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867
acetate on C-4, at the stage of iminium ion formation. Moreover, the enhanced stability of the enamine
intermediate resulted in the lower combined yield of the products. In the case of another primary amine,
n-butylamine, although the yield of 1c was slightly higher (36%) compared with the use of
cyclohexylamine, 3c (24%) was also obtained after acetylation. A bulkier substituent such as a
cyclohexyl group was advantageous in the equilibrium between the D-ido- and L-gluco-imines, but the
reason for the lower combined yield in the case of cyclohexylamine is not clear.
In addition, an attempt at the epimerization of aldehyde 8 itself, which was exposed to basic conditions
with KOH in aqueous EtOH,23 resulted in the formation of 11 in 21% yield after acetylation, but the
desired 1c was obtained only in a trace amount. E-Elimination of the hydroxy group at C-4 also
predominated, in this case, under strongly basic conditions.
In conclusion, benzyl 2,3-dideoxy-E-D-erythro-hex-2-enopyranoside (5b) was transformed to a protected
form of L-glucose (1c) with 19% overall yield in six steps. The π-facial selective epoxidation from the
E-side of the double bond between C-2 and C-3 of 5b proceeded smoothly. The subsequent ring
opening occurred exclusively at C-3 of 7, taking advantage of the E-substituent at the anomeric position.
Chemoselective oxidation at C-6 of 3b furnished an aldehyde 8. The inversion at C-5 with D-ido
stereochemistry was performed, presumably by way of N-cyclohexylenamine 10. The E-benzyloxy
group involved in this route was effective also at the stage of epimerization. As the present synthesis
keeps the whole skeleton and the order of carbon atoms based on the original numbering of D-glucose, it
would work well for the synthesis of specifically labeled derivatives, starting from isotopically labeled
D-glucoses.
EXPERIMENTAL
All mps are uncorrected. 1H-NMR spectra were measured at 500 MHz and 13C-NMR spectra were
measured at 125 MHz on an Agilent INOVA-500 spectrometer. IR spectra were measured as ATR on a
Jeol FT-IR SPX60 spectrometer. High resolution mass spectra were recorded on Jeol JMS-T100LP
AccuTOF. Optical rotation values were recorded on a Jasco P-1010 polarimeter. Silica Gel 60
(spherical and neutral; 100-210 μm, 37560-79) from Kanto Chemical Co. was used for column
chromatography. Preparative TLC was performed with Merck Silica Gel 60 F254 plates (0.5 mm
thickness, No. 5744).
3,6-Di-O-acetyl-4-O-methylsulfonyl-D-glucal (4d)
To a solution of 4c (500 mg, 2.17 mmol)14 in anhydrous CH2Cl2 (11 mL), triethylamine (454 μL, 3.26
mmol) was added under an argon atmosphere. After cooling to 0 °C, methylsulfonyl chloride (203 μL,
2.61 mmol) was added, and the mixture was stirred for 10 min at the same temperature. The progress of

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the reaction was checked by silica gel TLC, developed with CHCl3/MeOH (50:1), Rf for 4d: 0.61. After
consumption of starting material, the mixture was diluted with H2O and organic materials were extracted
with CHCl3 three times. The combined extract was washed sequentially with NaHCO3 aq solution and
brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was charged on a silica gel
column (20 mL). Elution with hexane/AcOEt (2:1) furnished 4d (672 mg, quantitative) as a yellow oil;
1H-NMR (CDCl3) δ: 2.10 (3H, s), 2.12 (3H, s), 3.08 (3H, s), 4.29 (1H, dd, J = 2.9, 5.1, 8.3), 4.30 (1H, dd,
J = 2.9, 12.5), 4.44 (1H, dd, J = 5.1, 12.5), 4.83 (1H, dd, J = 3.0, 6.2), 5.00 (1H, dd, J = 6.1, 8.3), 5.51
(1H, ddd, J = 1.2, 3.0, 6.1), 6.47 (1H, dd, J = 1.2, 6.2); 13C-NMR (CDCl3) δ: 20.39, 20.67, 38.37, 60.86,
67.38, 72.79, 73.63, 98.41, 145.51, 170.07, 170.26.
Benzyl 2,3-dideoxy-E-D-erythro-hex-2-enopyranoside (5b)
To a solution of 4d (669 mg, 2.17 mmol) in MeCN (22 mL) were added Cs2CO3 (1.41 g, 4.33 mmol) and
benzyl alcohol (4.53 mL, 43.5 mmol), and the mixture was stirred for 1.5 h at room temperature under an
argon atmosphere. The progress of the reaction was checked by silica gel TLC, developed with AcOEt,
Rf for 5b: 0.67; 6: 0.21. After consumption of starting material, the mixture was diluted with H2O and
organic materials were extracted with CHCl3 three times. The combined extract was washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was charged on a silica gel
column (40 mL). Elution with hexane/AcOEt (2:1) furnished 5b (414 mg, 81%) as a colorless solid; mp
80-81 °C; [D]D –107 (c 1.33, EtOH); IR cm−1: 3292, 2937, 2872, 1377, 1325, 1176, 1144, 1122, 1051,
22
970, 951, 876, 787, 744, 696; 1H-NMR (CDCl3) G: 1.97 (1H, d, J = 10.6), 2.21 (1H, dd, J = 5.9, 7.3), 3.79
(1H, ddd, J = 3.1, 4.3, 6.7), 3.88 (1H, ddd, J = 4.3, 7.3, 12.0), 3.97 (1H, ddd, J = 5.9, 6.7, 12.0), 4.02-4.09
(1H, m), 4.70 (1H, d, J = 11.8), 4.92 (1H, d, J = 11.8), 5.18 (1H, ddd, J = 1.1, 1.3, 1.5), 5.89 (1H, ddd, J =
13
1.0, 1.1, 10.0), 6.14 (1H, ddd, J = 1.3, 4.6, 10.0), 7.26-7.40 (5H, m); C-NMR (CDCl3) G: 62.5, 62.9,
70.3, 75.1, 96.5, 127.9, 128.0, 128.4, 130.2, 130.9, 137.2.
Further purification of more polar fractions of the above-mentioned chromatography with preparative
TLC developed with AcOEt twice furnished 6 as a colorless oil; 1H-NMR (CDCl3, 3:7 mixture of D- and
E-anomers) G: 3.70-4.08 (7H, m), 4.16 (0.7H, dd, J = 6.1, 10.3), 4.32 (0.3H, br,), 4.66 (1H, dd, J = 7.6,
12.4), 4.89 (1H, dd, J = 4.4, 12.4), 5.10-5.30 (2H, m), 5.82-5.96 (2H, m), 6.06-6.20 (2H, m), 7.26-7.40
(5H, m); HR-MS (ESI+) Calcd for C19H24NaO7 [M+Na]+ 387.1420, Found 387.1418.
Benzyl 2,3-dideoxy-2,3-epoxy-E-D-talopyranoside (7)
To a solution 5b (700 mg, 2.96 mmol) in MeCN (14 mL) were added KHCO3 (91 mg, 0.909 mmol) and
H2O2 (30% solution, 2.1 mL, 25.9 mmol), and the mixture was stirred for 5 h at room temperature. The
progress of the reaction was checked by silica gel TLC, developed with hexane/AcOEt (1:2), Rf for 7:

HETEROCYCLES, Vol. 95, No. 2, 2017
869
0.12. After consumption of starting material, the reaction was quenched with Na2S2O3 aq. solution, and
organic materials were extracted with AcOEt five times. The combined extract was washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was charged on a silica gel
column (30 mL). Elution with hexane/AcOEt (2:1) furnished 7 (598 mg, 80%) as a colorless solid; mp
115-116 °C; [D]D –80.7 (c 1.00, MeOH); IR cm−1: 3394, 2931, 2877, 1454, 1396, 1367, 1329, 1250,
21
1
1107, 1078, 1041, 906, 754, 698; H NMR (CDCl3) G: 3.42 (1H, ddd, J = 2.7, 4.9, 7.0), 3.34 (1H, d, J =
3.9), 3.58 (1H, dd, J = 3.9, 5.1), 3.77 (1H, dd, J = 4.9, 11.7), 3.83 (1H, dd, J = 7.0, 11.7), 3.93 (1H, br),
4.72 (1H, d, J = 12.1), 4.88 (1H, s), 4.95 (1H, d, J = 12.1), 7.28-7.42 (5H, m); 13C-NMR (CDCl3) G: 53.0,
53.8, 61.3, 61.8, 70.8, 77.5, 96.7, 128.1 (×3), 128.5 (×2), 136.8; HR-MS (ESI+) Calcd for C13H16NaO5
[M+Na]+ 275.0911, Found 275.0895.
Benzyl E-D-idopyranoside (3b)
To a solution of 7 (85 mg, 0.337 mmol) in H2O (6.7 mL) was added KOH (378 mg, 6.74 mmol), and the
mixture was stirred for 2.5 h at 120 °C (bath temperature). The progress of the reaction was checked by
silica gel TLC, developed with AcOEt, Rf for 3b: 0.24. After consumption of starting material, the
reaction was cooled to 0 °C and quenched with NH4Cl aq. solution, and organic materials were extracted
with AcOEt five times. The combined extract was washed with brine, dried over anhydrous Na2SO4,
and concentrated in vacuo. The residue was charged on a silica gel column (3 mL). Elution with
21
hexane/AcOEt (1:2) furnished 3b (74 mg, 81%) as a colorless amorphous solid; [D]D –75.2 (c 1.95,
1
MeOH); IR cm−1: 3358, 2891, 2362, 1456, 1018, 847, 733, 698; H-NMR (CD3OD) G: 3.52 (1H, dd, J =
1.5, 3.4), 3.61 (1H, dd, J = 0.9, 3.6), 3.77 (1H, dd, J = 6.8, 11.2), 3.82 (1H, dd, J = 6.8, 11.2), 3.88 (1H,
ddd, J = 1.5, 5.1, 6.8), 3.95 (1H, dd, J = 3.4, 3.6), 4.70 (1H, d, J = 11.9), 4.79 (1H, s), 4.93 (1H, d, J =
11.9), 7.24-7.42 (5H, m); 13C-NMR (CDCl3)ꢀG: 62.8, 70.3, 71.2, 71.4, 71.9, 76.5, 99.2, 128.8, 129.3 (×2),
129.4 (×2), 139.0; HR-MS (ESI+) Calcd for C13H18NaO6 [M+Na]+ 293.1002, Found 293.1001.
The stereochemistry of 3b was confirmed after conversion to the corresponding acetate 3c in a
1
conventional manner; H-NMR (CD3CN) G: 1.78 (3H, s), 1.80 (3H, s), 1.82 (3H, s), 1.83 (3H, s),
3.92-4.10 (3H, m), 4.39 (1H, d, J = 12.0), 4.58 (1H, dd, J = 2.2, 4.4), 4.63 (1H, d, J = 12.0), 4.67 (1H, dd,
J = 2.2, 4.4), 4.72 (1H, d, J = 2.2), 4.91 (1H, dd, J = 4.4, 4.4), 7.06-7.18 (5H, m).
Benzyl 2,3,4,6-tetra-O-acetyl-D-L-glucopyranoside (1c)
To a solution of 3b (41 mg, 0.152 mmol) in DMF (3.0 mL) were added NaHCO3 (382 mg, 4.55 mmol),
TEMPO (catalytic amount) and TCC (18 mg, 77.4 μmol) at 0 °C under an argon atmosphere. After
being stirred for 2.5 h at the same temperature, the reaction was quenched with Na2S2O3 aq. solution, and

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organic materials were extracted with AcOEt five times. The combined extract was washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo. This was employed for the next step without
further purification.
To the solution of the above-mentioned 8 in CH2Cl2 (3.0 mL) was added cyclohexylamine (17 μL, 0.148
mmol) at room temperature under an argon atmosphere. After being stirred for 24 h at the same
temperature, the reaction was quenched with H2O (10 mL), and concentrated in vacuo. This was
employed for the next step without further purification.
To the solution of the above-mentioned crude product in MeOH (3.0 mL) was added NaBH4 (29 mg,
0.767 mmol) at room temperature. After being stirred for 21 h at the same temperature, the reaction was
quenched with H2O (10 mL), and concentrated in vacuo to give crude 1b. This was employed for the
next step without further purification.
To the solution of the above-mentioned crude product in pyridine (758 μL) was added acetic anhydride
(143 μL, 1.51 mmol), and the mixture was stirred for 19 h at room temperature. The progress of the
reaction was checked by silica gel TLC, developed with hexane/AcOEt (2:1), Rf for 1c: 0.38. After
consumption of starting material, the reaction was cooled to 0 °C and quenched with NaHCO3 aq.
solution (2.0 mL), and organic materials were extracted with AcOEt three times. The combined extract
was washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was
charged on a silica gel column (5 mL). Elution with hexane/AcOEt (5:1) furnished 1c (19 mg, 29% in
four steps) as a colorless solid; mp 107-108 °C; [D]D –135.6 (c 1.00, CHCl3), [lit.22 [D]D +144.1 (c
2.01, CHCl3) for D-1c]; IR cm−1: 2360, 2341, 1367, 1215, 1034, 895, 739, 698; 1H-NMR (CDCl3) G: 2.01
(3H, s), 2.02 (3H, s), 2.03 (3H, s), 2.10 (3H, s), 4.01 (1H, dd, J = 2.5, 12.2), 4.04 (1H, ddd, J = 2.5, 4.2,
9.8), 4.24 (1H, dd, J = 4.2, 12.2), 4.57 (1H, d, J = 12.2), 4.73 (1H, d, J = 12.2), 4.88 (1H, dd, J = 3.9,
10.2), 5.09 (1H, dd, J = 9.5, 9.8), 5.13 (1H, d, J = 3.9), 5.53 (1H, dd, J = 9.5, 10.2), 7.28-7.40 (5H, m),
13C NMR (CDCl3) G: 20.60, 20.62, 20.69, 20.73, 61.7, 67.4, 68.5, 70.0, 70.1, 70.7, 95.0, 127.9 (×2), 128.2,
128.5 (×2), 136.6, 169.6, 170.0, 170.1, 170.7; HR-MS (ESI+) Calcd for C21H26NaO10 [M+Na]+ 461.1415,
Found 461.1424. Its spectral data were in good accordance with that of the enantiomer previously
reported.22
21
25
Side product 11: 1H-NMR (CDCl3) G: 2.01 (3H, s), 2.03 (3H, s), 2.08 (3H, s), 4.43 (1H, d, J =12.4), 4.45
(1H, d, J =12.4), 4.65 (1H, d, J =12.3), 4.84 (1H, d, J =12.3), 5.04 (1H, d, J = 2.8), 5.13 (1H, dd, J = 2.7,
7.6), 5.19 (1H, d, J = 2.7), 5.54 (1H, dd, J = 2.8, 7.6), 7.28-7.40 (5H, m).
ACKNOWLEDGEMENTS
This work was supported both by a Grant-in-Aid for Scientific Research (No. 26450143) and Platform for
Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports,

HETEROCYCLES, Vol. 95, No. 2, 2017
871
Science and Technology, Japan, and is gratefully acknowledged with thanks.
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