Synthesis of 3-O-β-D-glucopyranosyl-(3R)-hydroxybutanolide (Kinsenoside) and 3-O-β-D-glucopyranosyl-(3S)-hydroxybutanolide (Goodyeroside A)

Article abstract of DOI:10.1081/CAR-200050541

The first synthesis of 3-O-β-D-glucopyranosyl-(3R)-hydroxybutanolide (Kinsenoside) and 3-O-β-D-glucopyranosyl-(3S)-hydroxybutanolide (Goodyeroside A) is described. The diastereomers of the aglycon in 2-O-β-D-gulucopyranosyl-1,2,4-butanetriol derivatives, which were separable precursors of Kinsenoside and Goodyeroside A, were synthesized from optically nonactive 1,2,4-butanetriol and α-D-glucopyranosyl trichloroacetimidate in excellent yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/CAR-200050541

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Synthesis of
3‐O‐β‐D‐Glucopyranosyl‐(3R)‐hydroxybutanolide
(Kinsenoside) and
3‐O‐β‐D‐Glucopyranosyl‐(3S)‐hydroxybutanolide
(Goodyeroside A)
Katsuhiko Suzuki a , Nobuyuki Suzuki a , Masanori Yamaura a & Toyokichi Yoshizawa b
a Department of Enviromental Science, Faculty of Science and Engineering , Iwaki Meisei
University , Iwaki‐shi, Fukushima, Japan
b Seiwa Pharmaceutical, Ltd., Research and Development Division , Usuba,
Hanakawa‐machi, Kitaibarakishi, Ibaraki, Japan
Published online: 15 Aug 2006.
To cite this article: Katsuhiko Suzuki , Nobuyuki Suzuki , Masanori Yamaura & Toyokichi Yoshizawa (2005) Synthesis
of 3‐O‐β‐D‐Glucopyranosyl‐(3R)‐hydroxybutanolide (Kinsenoside) and 3‐O‐β‐D‐Glucopyranosyl‐(3S)‐hydroxybutanolide
(Goodyeroside A), Journal of Carbohydrate Chemistry, 24:1, 73-84, DOI: 10.1081/CAR-200050541
To link to this article: http://dx.doi.org/10.1081/CAR-200050541
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Journal of Carbohydrate Chemistry, 24:73–84, 2005
Copyright # Taylor & Francis, Inc.
ISSN: 0732-8303 print
DOI: 10.1081/CAR-200050541
Synthesis of 3-O-b-D-
Glucopyranosyl-(3R)-
hydroxybutanolide
(Kinsenoside) and 3-O-b-
D-Glucopyranosyl-(3S)-
hydroxybutanolide
(Goodyeroside A)
Katsuhiko Suzuki, Nobuyuki Suzuki and Masanori Yamaura
Department of Enviromental Science, Faculty of Science and Engineering,
Iwaki Meisei University, Iwaki-shi, Fukushima, Japan
Toyokichi Yoshizawa
Seiwa Pharmaceutical, Ltd., Research and Development Division, Usuba,
Hanakawa-machi, Kitaibarakishi, Ibaraki, Japan
The first synthesis of 3-O-b-D-glucopyranosyl-(3R)-hydroxybutanolide (Kinsenoside) and
3-O-b-D-glucopyranosyl-(3S)-hydroxybutanolide (Goodyeroside A) is described. The diaster-
eomers of the aglycon in 2-O-b-D-gulucopyranosyl-1,2,4-butanetriol derivatives, which were
separable precursors of Kinsenoside and Goodyeroside A, were synthesized from optically
nonactive 1,2,4-butanetriol and a-D-glucopyranosyl trichloroacetimidate in excellent yields.
Keywords Glycoside, Glycosylation, Lactone, Natural product, Oxidation
INTRODUCTION
Anoectochilus formosanus Hay has been used as a crude drug in Taiwan for
lung disease, pleurodynia, abdomenal pain, fever, hypertension, and snake
Received September 5, 2003; accepted October 24, 2003.
Address correspondence to Masanori Yamaura, Department of Enviromental Science,
Faculty of Science and Engineering, Iwaki Meisei University, 5-5-1 Iino, Chuohdai,
Iwaki-shi, Fukushima, 970-8551 Japan. Tel.: þ 81-246-29-7158; Fax: þ81-246-29-
0577; E-mail: yamaura@iwakimu.ac.jp
73

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bites.[1,2] In 1993, Ito and coworkers reported the isolation of a simple aliphatic
glucoside, which was characterized as 3-O-b-D-glucopyranosyl-(3R)-hydroxy-
butanolide 1 (Kinsenoside), from Anoectochilus koshunensis.[3] Several bio-
active molecules related to Kinsenoside were also found from an undefined
Anoectochilus species.[4] From a study of the components of A. formosanus,
butanoic acid glucosides have been of great interest.[5] However, the structure-
bioactivity relationship had not been studied because of the difficulty of the
cultivation of A. formosanus Hay. Goodyeroside A 2, which is a diastereomer
of 1 on the aglycon part, is expected as a substitute of 1,[6] but there is not suffi-
cient information about its bioactivity to use as a drug. To study the structure-
bioactivity relationship, we planned the synthesis of 1 and 2 (Fig. 1). In this
communication, we would like to report an efficient large-scale synthesis of 1
and 2 and related analogue synthesis.
RESULTS AND DISCUSSION
The chemical stability of 1 and 2, which are easily decomposed by the
b-elimination of an aglycon moiety to give glucose under the basic conditions,
is important in planning the synthetic route. We suggest that the aglycon
residue is constructed by oxidation of the hydroxymethyl group after the
regio- and stereoselective glycosylation. The synthetic strategy based on the
glycosylation of a 1,2,4-butanetriol derivative is shown in Fig. 2.
Many types of 1,2,4-butanetriol derivatives are commercially available.
However, optically active forms are very expensive and difficult to use in
large-scale synthesis. We tried to use the optically nonactive 1,2,4-butanetriol
and to separate the diastereomers after construction of the glycosidic linkage.
A partly protected 1,2,4-butanetriol for the glycosylation was synthesized as
shown in Sch. 1.
Construction of the b-glucoside was accomplished using the imidate
method (Sch. 2).[7] Reaction of 2,3,4,6-tetra-O-benzoyl-a-D-glucopyranosyl tri-
chloroacetimidate 8 with butanetriol 7 in CH2Cl2 at room temperature in the
presence of Me3SiOTf (1 equiv.) gave the corresponding b-glucoside 9 as a 1:1
diastereomeric mixture on the aglycon part. Deprotection of the O-allyl
[8]
group of 9 by use of PdCl2 gave alcohols 10 (R, S) as chromatographically
Figure 1: Structures of Kinsenoside and Goodyeroside A.

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Figure 2: Synthetic plan of 1 and 2.
separable diastereomers. Compound 10 (R, S) was individually oxidized to
carboxylic acid 11 (R, S) by the agency of the ruthenium reagent.[9] Under
this condition, the benzyl group was also oxidized to the benzoyl group. De-
O-benzoylation of compound 12 (R, S) gave Kinsenoside and Goodyeroside A
as the acid form, which were converted to Kinsenoside 1 and Goodyeroside A
2 by treatment with acid from ion-exchange resin (DOWEXw 50WX-4) in
H2O. The spectral data of 1 and 2 were in good agreement with the reported
data of the natural product.[5,10] The structure of 1 was already confirmed by
X-ray analysis of the peracetate.[5] The structure of 2 was newly confirmed
by a comparison with the spectral data of perbenzoate 14 derived from 2
(Sch. 3). Treatment of 2 with benzoyl chloride in pyridine gave a perbenzoate
derivative 14 in a good yield. This compound was also synthesized from opti-
cally active (3S)-hydroxybutylolactone 13 and imidate 8, and the spectral
data agreed with those of 14 derived from 2.
Scheme 1: Synthesis of partly protected 1,2,4-butanetriol derivative: (a) TsOH, acetone;
(b) Allyl bromide, NaH, DMF; (c) DOWEXw 50WX-4, MeOH; (d) (n-Bu)2SnO, toluene then BnBr,
CsF, DMF.

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Scheme 2: Synthesis of 1 and 2: (a) 7, Me3SiOTf, Molecular sieves AW-300, CH2Cl2, 08C;
(b) PdCl2, AcONa-AcOH buffer (pH ¼ 4.5), 1,4-dioxane; (c) RuCl3, NaIO4, CCl4, CH3CN, H2O;
(d) NaOMe, MeOH; (e) DOWEXw 50WX-4, H2O.
Thus, Kinsenoside 1 and Goodyeroside A 2 were synthesized by the same
route with construction of the aglycon residue after the regio- and stereoselec-
tive glycosylation. This method is promising for the supply of related analogues
of 1 and 2.
EXPERIMENTAL
General Methods
Optical rotations were measured at 258C with a HORIBA polarimeter
SEPA-300. NMR spectra were measured on a JEOL JNM-ECP 400
Scheme 3: Synthesis of tetra-benzoate 14: (a) 8, Me3SiOTf, Molecular sieves AW-300, CH2Cl2,
08C; (b) BzCl, pyridine.

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1
spectrometer (400 MHz). H-NMR were recorded in CDCl3, CD3OD, or D2O
using Me4Si (d 0.00) or DOH (d 4.81) as the internal standard. 13C-NMR
spectra were recorded in CDCl3, CD3OD, or D2O using CDCl3 (d 77.0),
CD3OD (d 49.0), acetone (d 30.3), or 1,4-dioxane (d 67.6) as the internal
standard. Coupling constants were measured in Hz. Silica gel column chroma-
tography was performed using Wakogel C-300 (Wako Pure Chemical Indus-
tries, Ltd.). Analytical TLC was performed on aluminium plates coated with
silica gel 60 F254 (Merck). Molecular sieves were purchased from Aldrich
Chemical Company, Inc., and activated at 1808C under vacuum immediately
prior to use.
(+)-1,2-O-Isopropylidene-1,2,4-butanetriol (4)
To an acetone solution (50 mL) of 3 (3.0 g, 28 mmol) were added CuSO4
(13.5 g, 84.9 mmol) and p-TsOH (5.4 g, 28.3 mmol). After being stirred for 6 hr
at room temperature, the reaction mixture was poured into 1 M NaOH and
the insoluble component was filtered. Most of acetone in the filterate was eva-
porated and the residue was diluted with EtOAc, washed with brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified by silica gel
column chromatography (n-hexane: EtOAc ¼ 1:1 ꢀ 0:1) to afford 4 (3.3 g,
80%) as an oil; 1H-NMR (CDCl3) d 4.26 (qt, 1H, H-2, J ¼ 6.2 Hz), 4.09
(dd, 1H, H-1a, J ¼ 6.2, 7.9 Hz), 3.77 (m, 2H, H-4), 3.59 (dd, 1H, H-1b, J ¼ 7.9,
7.9 Hz), 2.93 (br s, 1H, OH), 1.85–1.79 (m, 2H, H-3), 1.42 and 1.36 (each s,
6H, acetonide); 13C-NMR (CDCl3) d 108.79, 74.51 (C-2), 69.28 (C-1), 59.89
(C-4), 35.63 (C-3), 26.71, 25.51. Anal. Calcd for C7H14O3: C, 57.51; H, 9.65.
Found: C, 57.36; H, 9.76.
(+)-1,2-O-Isopropylidene-4-O-allyl-1,2,4-butanetriol (5)
To a DMF (5 mL) solution of 4 (320 mg, 2.20 mmol) was added NaH (128 mg,
4.40 mmol) at 08C. After being stirred for 30 min, to the mixture was added allyl
bromide (AllBr, 0.462 mL, 0.44 mmol) dropwise at a temperature kept below
08C. After being stirred for 6 hr at rt, the mixture was poured into saturated
aqueous NH4Cl (600 mL) and extracted with EtOAc (100 mL ꢀ 3). The
combined organic layer was washed with brine, dried (MgSO4), and concen-
trated in vacuo. The residue was purified by silica gel column chromatography
(n-hexane: EtOAc ¼ 9:1 ꢀ 4:1) to give 5 (4.13 g, 98%) as an oil; 1H-NMR
(CDCl3) d 5.95–5.85 (m, 1H, CH2-CH55CH2), 5.26 (br d, 1H, CH2-CH55CH2,
J ¼ 17.2 Hz), 5.17 (br d, 1H, CH2-CH55CH2, J ¼ 10.3 Hz), 4.20 (qt, 1H,
H-2, J ¼ 7.0 Hz), 4.06 (br t, 1H, H-1a, J ¼ 7.0 Hz), 3.96 (br d, 2H,
CH2-CH55CH2, J ¼ 5.5 Hz), 3.59–3.48 (m, 3H, H-1b, 4a, 4b), 1.93–1.80
(m, 2H, H-3), 1.40 and 1.35 (each s, 6H, acetonide); 13C-NMR (CDCl3)
d 134.62, 116.63, 108.36, 73.71 (C-2), 71.77, 69.51 (C-1), 66.82 (C-4), 33.74
(C-3), 26.80, 25.64. Anal. Calcd for C10H18O3: C, 64.49; H, 9.74. Found: C,
64.58; H, 9.66.

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78
To a MeOH (2 mL) solution of 5 (200 mg, 1.07 mmol) were added Dowexw
50WX-4 (ca. 50 mg) and H2O (2 mL). After being stirred for 22 hr at rt, the
mixture was filtered and concentrated in vacuo to afford 6 (157 mg, quant.)
1
as an oil; H-NMR (CD3OD) d 5.96–5.86 (m, 1H, CH2-CH55CH2), 5.26 (br d,
1H, CH2-CH55CH2, J ¼ 17.2 Hz), 5.15 (br d, 1H, CH2-CH55CH2, J ¼ 10.3 Hz),
3.98 (d, 2H, CH2-CH55CH2, J ¼ 5.5 Hz), 3.77–3.71 (m, 1H, H-2), 3.63–3.54
(m, 2H, H-4), 3.49 (dd, 1H, H-1a, J ¼ 4.8, 11.2 Hz), 3.44 (dd, 1H, H-1b,
J ¼ 6.2, 11.2 Hz), 1.83–1.75 (m, 1H, H-3a), 1.66–1.57 (m, 1H, H-3b); 13C-
NMR (CDCl3) d 136.13, 117.05, 72.78, 70.61 (C-2), 68.11 (C-4), 67.37 (C-1),
34.42 (C-3). Anal. Calcd for C7H14O3: C, 57.51; H, 9.65. Found: C, 57.57; H, 9.73.
(+)-4-O-Allyl-1-O-benzyl-1,2,4-butanetriol (7)
To a toluene (50 mL) solution of 6 (2.35 g, 16.2 mmol) was added (n-Bu)2SnO
(4.83 g, 19.4 mol). After being stirred for 3 hr at reflux temperature, the solvent
was removed by evaporation. To a DMF (30 mL) solution of the residue were
added CsF (5.4 g, 36 mol) and BnBr (2.02 mL, 17.0 mol), and the mixture was
stirred for 12 hr at 08C. The reaction mixture was poured into 1M NaOH
(700 mL) and extracted with EtOAc (100 mL ꢀ 3). The combined organic
layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The
residue was purified by silica gel column chromatography (n-hexane:
EtOAc ¼ 1:0 ꢀ 3:1) to give 7 (2.8 g, 73%) as a syrup; 1H-NMR (CDCl3) d
7.35–7.30 (m, 5H, phenyl), 5.92–5.83 (m, 1H, CH2-CH55CH2), 5.25 (d, 1H,
CH2-CH55CH2, J ¼ 17.2 Hz), 5.16 (d, 1H, CH2-CH55CH2, J ¼ 11.0 Hz), 4.53
(s, 2H, benzyl), 4.02–3.95 (m, 1H, H-2), 3.95 (d, 2H, CH2-CH55CH2,
J ¼ 5.9 Hz), 3.61 (ddd, 1H, H-4a, J ¼ 9.5, 6.2, 6.2 Hz), 3.56 (ddd, 1H, H-4b,
J ¼ 9.5, 6.2, 6.2 Hz), 3.47 (dd, 1H, H-1a, J ¼ 4.0, 9.5 Hz), 3.40 (dd, 1H,
H-1b, J ¼ 7.0, 9.5 Hz), 3.22 (br s, 1H, OH), 1.77–1.72 (m, 2H, H-3); 13C-NMR
(CDCl3) d 137.89, 134.42, 128.27, 127.61, 126.80, 116.89, 74.18, 73.15, 71.83,
68.89, 67.61, 32.98. Anal. Calcd for C14H20O3: C, 71.16; H, 8.53. Found: C,
71.45; H, 8.29.
4-O-Allyl-1-O-benzyl-2-O-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl)-
1,2,4-butanetriol (9)
The mixture of acceptor 7 (0.78 g, 5.94 mmol), imidate 8 (2.20 g, 2.97 mmol),
˚
and molecular sieves 4A (AW-300, ca. 1 g) in CH2Cl2 (50 mL) was stirred for 2 hr
at room temperature under an argon atmosphere. To this mixture was added
Me3SiOTf (0.66 g, 2.97 mmol) at 08C. After being stirred for 10 min, the
reaction was stopped by addition of Et3N (3.00 g, 29.7 mmol). The solution
was filtered and concentrated in vacuo. The residue was purified by silica
gel column chromatography (n-hexane:EtOAc ¼ 5:1) to afford 9R and 9S
(2.30 g, 95%) as an unseparable mixture (9R:9S ¼ 1:1); 1H-NMR (CDCl3)

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d 8.07–7.84 and 7.56–7.19 (m, 25H, phenyl), 5.94 (dd, 0.5H, H-30, J ¼ 9.9,
9.9 Hz), 5.92 (dd, 0.5H, H-30, J ¼ 9.9, 9.9 Hz), 5.87–5.72 (m, 1H, CH2-
CH55CH2), 5.72 (dd, 0.5H, H-40, J ¼ 9.9, 9.9 Hz), 5.67 (dd, 0.5H, H-40, J ¼ 9.9,
9.9 Hz), 5.58 (dd, 0.5H, H-20, J ¼ 9.9, 8.4 Hz), 5.56 (dd, 0.5H, H-20, J ¼ 9.9,
8.4 Hz), 5.21 (d, 0.5H, H-10, J ¼ 8.4 Hz), 5.15–5.08 (m, 2H, CH2-CH55CH2),
5.01 (d, 0.5H, H-10, J ¼ 8.4 Hz), 4.65 (dd, 0.5H, H-60a, J ¼ 2.9, 8.8 Hz), 4.62
(dd, 0.5H, H-60a, J ¼ 2.9, 8.8 Hz), 4.52–4.44 (m, 2H, H-60b and benzyl), 4.30,
4.23 (each d, 1H, benzyl, J ¼ 12.10Hz), 4.17–4.11 (m, 1.5H, H-2 and H-50),
4.04–3.98 (m, 0.5H, H-2), 3.92–3.81 (m, 2H, CH2-CH55CH2), 3.72–3.26
(m, 4H, H-1 and H-4), 1.92–1.73 (m, 2H, H-3); 13C-NMR (CDCl3) d 166.09,
166.07, 165.83, 165.21, 165.16, 164.90, 138.28, 138.05, 134.94, 134.77,
133.38–133.10, 129.81–127.33, 116.60, 116.51, 101.78, 100.85, 77.97, 77.24,
76.17, 73.86, 73.23, 73.08, 73.02, 72.73, 72.19, 72.11, 71.94, 71.78, 71.49,
69.81, 66.43, 65.97, 63.21, 63.09, 32.34.
1-O-Benzyl-2-O-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl)-1,2,4-butanetriol
(10R, 10S)
To a 1,4-dioxane solution (2 mL) of the mixture (9R:9S ¼ 1:1, 105 mg,
0.129 mmol) were added an acetic acid buffer (pH 4.5, 2 mL) and PdCl2
(46 mg, 0.26 mmol). After being stirred for 24 hr at room temperature, the
solution was diluted with CH2Cl2 (ca. 10 mL), washed with saturated
aqueous NaHCO3 (ca. 50 mL), dried over MgSO4, and concentrated in vacuo.
The residue was purified by silica gel column chromatography (n-hexane:
EtOAc ¼ 9:1 ꢀ 4:6) to afford 10R (27 mg, 27%) and 10S (27 mg, 27%), respect-
ively. Compound 10R: [a]D þ 27.28 (c 0.47, CH2Cl2); mp: 152 ꢀ 1548C (crystal-
ized from EtOH and n-hexane); Rf ¼ 0.2 (n-hexane:EtOAc ¼ 6:4); 1H-NMR
(CDCl3) d 8.03–7.23 (m, 25H, phenyl), 5.89 (dd, 1H, H-30, J ¼ 9.9, 9.7 Hz),
5.65 (dd, 1H, H-40, J ¼ 9.5, 9.7 Hz), 5.52 (dd, 1H, H-20, J ¼ 7.9, 9.7 Hz), 5.03
(d, 1H, H-10), 4.61 (dd, 1H, H-60a, J ¼ 3.3, 12.1 Hz), 4.46 (dd, 1H, H-60b,
J ¼ 5.1, 12.1 Hz), 4.47, 4.43 (each d, 2H, benzyl, J ¼ 11.7 Hz), 4.12 (ddd, 1H,
H-50, J ¼ 3.3, 5.1, 9.5 Hz), 4.02 (m, 1H, H-3), 3.71 (dd, 1H, H-4a, J ¼ 4.8,
10.1 Hz), 3.55 (dd, 1H, H-4b, J ¼ 5.9, 10.1 Hz), 3.51 (m, 2H, H-1a, 1b), 1.77
(m, 2H, H-2a, 2b), 1.54 (br s, 1H, OH); 13C-NMR (CDCl3) d 166.07, 165.78,
165.19, 165.10, 137.96, 133.44, 133.42, 133.22, 133.15, 129.74, 129.72, 128.40,
128.34, 127.61, 101.55 (C-10), 78.25 (C-3), 73.38 (benzyl), 72.91 (C-30), 72.67
(C-4), 72.23 (C-20), 72.20 (C-50), 69.74 (C-40), 63.14 (C-60), 58.72 (C-1), 34.94
(C-2). Anal. Calcd for C45H42O12:C, 69.76; H, 5.46. Found: C, 70.03; H, 5.47.
Compound 10S: [a]D þ 3.88 (c 0.49, CH2Cl2); Rf ¼ 0.3 (n-hexane:EtOAc ¼ 6:4);
1H-NMR (CDCl3) d 8.13–7.18 (m, 25H, phenyl), 5.96 (dd, 1H, H-30, J ¼ 9.5,
9.9 Hz), 5.69 (dd, 1H, H-40, J ¼ 9.9, 9.5 Hz), 5.54 (dd, 1H, H-20, J ¼ 7.7,
9.9 Hz), 5.24 (d, 1H, H-10, J ¼ 7.7 Hz), 4.89 (dd, 1H, H-60a, J ¼ 2.6, 12.5 Hz),
4.39 (dd, 1H, H-60b, J ¼ 5.5, 12.5 Hz), 4.32, 4.21 (each d, 2H, benzyl,
J ¼ 12.1 Hz), 4.24–4.15 (m, 2H, H-3, H-50), 3.86 (m, 1H, H-1b), 3.40 (dd, 1H,

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H-4a, J ¼ 3.3, 10.3 Hz), 3.35 (dd, 1H, H-4b, J ¼ 7.3, 10.3 Hz), 2.84 (br s, 1H,
OH), 1.69 (m, 1H, H-2a), 1.56 (m, 1H, H-2b); 13C-NMR (CDCl3) d 166.31,
166.74, 165.20, 165.11, 137.86, 133.50, 133.30, 133.18, 133.12, 129.82–
128.24, 101.08 (C-10), 75.59 (C-3), 74.20 (C-4), 73.28 (benzyl), 72.81 (C-30),
72.35 (C-50), 71.97 (C-20), 69.46 (C-40), 62.53 (C-60), 58.07 (C-1), 33.97 (C-2).
Anal. Calcd for C45H42O12: C, 69.76; H, 5.46. Found: C, 69.67; H, 5.74.
4-O-Benzoyl-3-O-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl)-(3R)-
3,4-dihydroxy-butanoic Acid (11R)
To a solution (CCl4; 1.2 mL, MeCN; 1.2 mL, and H2O; 1.8 mL) of 10R (20 mg,
26 ꢀ 1023 mmol) were added NaIO4 (17 mg, 77 ꢀ 1023 mmol) and RuCl3 (1 mg,
4.8 ꢀ 1023 mmol). After being stirred for 18 hr at room temperature, the
solution was diluted with CH2Cl2 (ca. 10 mL), washed with 1M HCl (ca.
50 mL), dried over MgSO4, and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-hexane:EtOAc ¼ 1:1 ꢀ 1:2)
to afford 11R (19 mg, 90%); [a]D þ 5.98 (c 0.41, acetone); mp: 193 ꢀ 1958C
1
(crystalized from acetone and n-hexane); H-NMR (CDCl3) d 8.00–7.81 and
7.52–7.25 (m, 25H, phenyl), 5.97 (dd, 1H, H-30, J ¼ 9.7, 9.7 Hz), 5.64 (dd, 1H,
H-40, J ¼ 9.7, 9.7 Hz), 5.53 (dd, 1H, H-20, J ¼ 7.9, 9.7 Hz), 5.15 (d, 1H, H-10,
J ¼ 7.9 Hz), 4.60 (1H, dd, H-4a, J ¼ 4.8, 12.1 Hz), 4.59 (dd, 1H, H-60a,
J ¼ 2.9, 12.1 Hz), 4.50 (ddd, 1H, H-3, J ¼ 4.8, 5.9, 6.2 Hz), 4.43 (1H, dd,
H-60b, J ¼ 5.5, 12.1 Hz), 4.35 (dd, 1H, H-4b, J ¼ 5.9, 12.1 Hz), 3.22 (ddd, 1H,
H-50, J ¼ 2.9, 5.5, 9.7 Hz), 2.60 (d, 2H, H-2, J ¼ 6.2 Hz); 13C-NMR (CDCl3) d
174.62, 166.06, 166.01, 165.83, 165.19, 165.03, 133.43, 133.26, 133.17, 133.14,
133.04, 129.79–128.28, 101.83, 74.98, 72.81, 72.24, 71.85, 69.65, 65.81, 63.02,
37.11. Anal. Calcd for C46H38O14:C, 67.33; H, 4.77. Found: C, 67.15; H, 4.74.
4-O-Benzoyl-3-O-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl)-(3S)-
3,4-dihydroxy-butanoic Acid (11S)
Compound 11S was obtained from 10S in the same manner as described for
1
11R (90%); [a]D þ 13.68 (c 0.47, acetone); H-NMR (CDCl3) d 8.01–7.71 and
7.55–7.15 (m, 25H, phenyl), 5.88 (dd, H-30, J ¼ 9.7, 9.7 Hz), 5.70 (dd, 1H,
H-40, J ¼ 9.7, 9.7 Hz), 5.52 (dd, 1H, H-20, J ¼ 8.1, 9.7 Hz), 5.08 (d, 1H, H-10,
J ¼ 8.1 Hz), 4.73 (dd, 1H, H-60a, J ¼ 3.7, 12.1 Hz), 4.59–4.53 (m, 1H, H-3),
4.49 (dd, 1H, H-60b, J ¼ 4.0, 12.1 Hz), 4.28 (d, 2H, H-4, J ¼ 5.1 Hz), 4.10 (ddd,
1H, H-50, J ¼ 3.4, 4.0, 9.7 Hz), 2.85 (dd, 1H, H-2a, J ¼ 7.3, 16.1 Hz), 2.65 (dd,
1H, H-2b, J ¼ 5.1, 16.1 Hz); 13C-NMR (CDCl3) d 173.13, 166.61, 165.94,
165.74, 165.16, 165.01, 133.46, 133.42, 133.22, 133.08, 133.04, 129.85–
128.22, 101.35, 75.33, 72.74, 72.18, 71.72, 69.77, 65.77, 62.90, 37.63. Anal.
Calcd for C46H38O14: C, 67.33; H, 4.77. Found: C, 67.23; H, 4.85.

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3-O-(b-D-Glucopyranosyl)-(3R)-3,4-dihydroxy-butanoic Acid (12R)
To a NaOMe (2mg, 4 ꢀ 1022 mmol) in MeOH (0.4 mL) solution (0.1 M) was
added 11R (19 mg, 24 ꢀ 1023 mmol). After being stirred for 3 hr, the mixture
was diluted with H2O (10 mL) and washed with CH2Cl2 (2mL). The water
layer was neutralized with DOWEXw 50WX-4 and evaporated in vacuo to
afford 12R (5.0 mg, 75%) as a syrup. Compound 12R was identified by comparison
1
with an authentic sample; H-NMR (D2O) d 4.59 (d, 1H, H-10, J ¼ 7.9 Hz),
4.24–4.18 (m, 1H, H-3), 3.92 (dd, 1H, H-60a, J ¼ 2.2, 12.4 Hz), 3.75–3.71
(m, 2H, H-4a and H-60b), 3.62 (dd, 1H, H-4b, J ¼ 6.2, 12.1 Hz), 3.52 (dd, 1H,
H-30, J ¼ 9.2, 9.9 Hz), 3.51–3.47 (m, 1H, H-50), 3.40 (dd, 1H, H-40, J ¼ 9.9,
9.9 Hz), 3.29 (dd, 1H, H-20, J ¼ 7.9, 9.2 Hz), 2.51 (dd, 1H, H-2a, J ¼ 7.0,
14.7 Hz), 2.44 (dd, 1H, H-2b, J ¼ 5.9, 14.7 Hz); 13C-NMR (D2O) d 179.44,
101.75, 78.94, 75.94, 75.62, 73.36, 69.70, 63.92, 60.80, 39.67. (lit.)[5] [a]D 25.88
1
(c 1.2, MeOH); Positive FAB-MS: m/z 283 [M þ H]þ; H-NMR (CD3OD) d 4.44
(d, 1H, H-10, J ¼ 7.9 Hz), 4.12 (dddd, 1H, H-3, J ¼ 7.3, 5.9, 5.9, 4.3 Hz), 3.85
(dd, 1H, H-60a, J ¼ 1.7, 11.9 Hz), 3.65 (dd, 1H, H-60 b, J ¼ 6.1 Hz), 3.64 (dd, 1H,
H-4, J ¼ 4.3, 12.5 Hz), 3.59 (dd, 1H, H-4b, J ¼ 5.9 Hz), 3.37 (dd, 1H, H-30,
J ¼ 8.9, 8.9 Hz), 3.30 (dd, 1H, H-40, J ¼ 8.9 Hz), 3.36 (m, 1H, H-50), 3.19 (dd,
1H, H-20), 2.47 (dd, 1H, H-2a, J ¼ 7.3, 14.9 Hz), 2.38 (dd, 1H, H-2b, J ¼ 5.9 Hz);
13C-NMR (CD3OD) d 179.6, 104.1, 80.3, 78.0, 77.9, 75.4, 71.5, 66.0, 62.7, 41.3.
3-O-(b-D-Glucopyranosyl)-(3S)-3,4-dihydroxy-butanoic Acid (12S)
Compound 12S was obtained from 11S in the same manner as described for
12R (82%); Compound 12S was identified by comparison with an authentic
1
sample; H-NMR (D2O) d 4.59 (d, 1H, H-10, J ¼ 8.3 Hz), 4.25–4.18 (m, 1H,
H-3), 3.89 (d, 1H, H-60a, J ¼ 12.1 Hz), 3.74–3.61 (m, 3H, H-4a, H-4b and
H-60b), 3.50 (dd, 1H, H-30, J ¼ 9.0, 9.4 Hz), 3.45–3.39 (m, 1H, H-50), 3.37 (dd,
1H, H-40, J ¼ 9.2, 9.4 Hz), 3.29 (dd, 1H, H-20, J ¼ 8.3, 9.0 Hz), 2.54 (dd, 1H,
H-2a, J ¼ 7.3, 15.0 Hz), 2.42 (dd, 1H, H-2b, J ¼ 5.9, 15.0 Hz). (lit.)[10] [a]D
219.38 (c 0.4, H2O); Positive FAB-MS: m/z 283 (M þ H)þ, 305 (M þ Na)þ;
Negative FAB-MS: m/z 281 (M 2 H)2; HR-FAB-MS: m/z 281.0883 (M 2 H)2
1
(Calcd for C10H17O9 281.0872); H-NMR (CD3OD) d 4.43 (d, 1H, H-10,
J ¼ 7.9 Hz), 4.15 (m, 1H, H-3), 3.86 (dd, 1H, H-60a, J ¼ 2.0, 11.9 Hz), 3.66 (dd,
1H, H-60b, J ¼ 5.1 Hz), 3.63 (dd, 1H, H-4a, J ¼ 4.5, 12.3 Hz), 3.58 (dd, 1H,
H-4b, J ¼ 5.9 Hz), 3.35 (dd, 1H, H-30, J ¼ 8.9, 8.9 Hz), 3.34 (m, 1H, H-50), 3.22
(dd, 1H, H-40, J ¼ 8.9 Hz), 3.18 (dd, 1H, H-20), 2.57 (dd, 1H, H-2a, J ¼ 6.9,
15.5 Hz), 2.48 (dd, 1H, H-2b, J ¼ 5.6 Hz); 13C-NMR (CD3OD) d 177.2, 104.1,
79.7, 78.0, 78.0, 75.2, 71.6, 65.6, 62.7, 38.9.
3-O-(b-D-Glucopyranosyl)-(3R)-hydroxy-butylolactone (1)
To a H2O (0.4 mL) solution of 12R was added DOWEXw 50WX-4 (ca. 20 mg).
After being stirred for 18 hr, the resin was filtered and the filtrate was

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concentrated in vacuo to afford 1 (4.6 mg, 98%). Compound 1 was identified
1
by comparison with an authentic sample; [a]D þ 48.48 (c 2.0, EtOH); H-NMR
(D2O) d 4.61 (d, 2H, H-4a and H-4b, J ¼ 2.9 Hz), 4.56 (d, 1H, H-10,
J ¼ 7.7 Hz), 3.92 (dd, 1H, H-60a, J ¼ 2.2, 12.5 Hz), 3.73 (dd, 1H, H-60b,
J ¼ 5.5, 12.5 Hz), 3.50 (dd, 1H, H-30, J ¼ 9.2, 9.2 Hz), 3.47 (ddd, 1H,
H-50, J ¼ 2.2, 5.5, 9.5 Hz), 3.40 (dd, 1H, H-40, J ¼ 9.2, 9.5 Hz), 3.28 (dd, 1H,
H-20, J ¼ 7.7, 9.2 Hz), 3.01 (dd, 1H, H-2a, J ¼ 6.2, 18.3 Hz), 2.73 (d, 1H, H-2b,
[5]
J ¼ 18.3 Hz). (lit.)
Positive FAB-MS: m/z 265 (M þ H)þ, 287 (M þ Na)þ;
1H-NMR (pyridine-d5) d 4.90 (d, 1H, H-10, J ¼ 7.9 Hz), 4.87 (m, 1H, H-3), 4.71
(dd, 1H, H-4a, J ¼ 1.6, 10.2 Hz), 4.55 (dd, 1H, H-60a, J ¼ 2.3, 11.8 Hz), 4.43
(dd, 1H, H-4b, J ¼ 4.6 Hz), 4.35 (dd, 1H, H-60b, J ¼ 5.6 Hz), 4.24 (m, 1H,
H-30), 4.21 (m, 1H, H-40), 3.95 (m, 1H, H-50), 2.85 (m, 2H, H-2a and H-2b);
13C-NMR (pyridine-d5) d 175.9, 104.1, 78.7, 78.3, 75.2, 74.8, 74.7, 71.4,
62.7, 35.7.
3-O-(b-D-Glucopyranosyl)-(3S)-hydroxy-butylolactone (2)
Compound 2 was obtained from 12S in the same manner as described for
1 (99%); Compound 2 was identified by comparison with an authentic
1
sample; [a]D 271.08 (c 0.5, H2O); H-NMR (D2O) d 4.62 (d, 1H, H-10,
J ¼ 7.7 Hz), 4.59 (br s, 2H, H-4a, H-4b), 3.95 (d, 1H, H-60a, J ¼ 12.8 Hz), 3.76
(dd, 1H, H-60b, J ¼ 5.5, 12.8 Hz), 3.54 (dd, 1H, H-30, J ¼ 9.2, 9.2 Hz), 3.50
(m, 1H, H-50, J ¼ 5.5, 9.2 Hz), 3.43 (dd, 1H, H-40, J ¼ 9.2, 9.2 Hz), 3.31 (dd,
1H, H-20, J ¼ 7.7, 9.2 Hz), 3.07 (dd, 1H, H-2a, J ¼ 6.2, 18.3 Hz), 2.83 (d, 1H,
H-2b, J ¼ 18.3 Hz). (lit.)[10] mp: 156 ꢀ 1578C (crystalized from EtOH); [a]D
271.28 (c 0.55, H2O); Positive FAB-MS: m/z 265 (M þ H)þ, 287 (M þ Na)þ;
HR-FAB-MS: m/z 287.0843 (M þ Na)þ (Calcd for C10H16O8Na 287.0845);
1H-NMR (pyridine-d5) d 4.94 (d, 1H, H-10, J ¼ 7.9 Hz), 4.85 (m, 1H, H-3), 4.69
(dd, 1H, H-4a, J ¼ 1.5, 10.2 Hz), 4.54 (dd, 1H, H-60a, J ¼ 2.3, 11.7 Hz), 4.41
(dd, 1H, H-4b, J ¼ 4.7 Hz), 4.35 (dd, 1H, H-60b, J ¼ 5.3 Hz), 4.22 (dd, 1H,
H-30, J ¼ 8.9, 8.9 Hz), 4.19 (dd, 1H, H-40, J ¼ 8.9 Hz), 3.98 (dd, 1H, H-20), 3.94
(m, 1H, H-50), 2.88 (dd, 1H, H-2a, J ¼ 5.2, 17.8 Hz), 2.84 (dd, 1H, H-2b,
J ¼ 2.5 Hz); 13C-NMR (pyridine-d5) d 176.2, 103.7, 78.7, 78.4, 74.8, 74.7, 74.0,
71.5, 62.8, 36.4.
3-O-(2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl)-(3S)-3-hydroxy-
butylolactone (14)
From 2 To a pyridine solution (0.1 mL) of 2 (3.0 mg, 11 ꢀ 1023 mmol) was
added benzoyl chloride (6.6 mL, 57 ꢀ 1023 mmol). After being stirred for 17 hr
at room temperature, the reaction was stopped by addition of MeOH (ca.
2 mL). The solution was concentrated and the residue was purified by
silica gel column chromatography (n-hexane:EtOAc ¼ 2:1 ꢀ 1:1) to afford 14
(7.0 mg, 90%). From 13: The mixture of acceptor 13 (88 mg, 0.86 mmol),
˚
imidate 8 (320 mg, 0.432 mmol), and molecular sieves 4A (AW-300, ca. 1 g) in

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CH2Cl2 (5 mL) was stirred for 1 hr at room temperature under an argon atmos-
phere. To this mixture was added Me3SiOTf (96 mg, 0.43 mmol) at 08C. After
being stirred for 30 min, the reaction was stopped by addition of Et3N (1.03 g,
4.32 mmol). The solution was filtered and concentrated in vacuo. The residue
was purified by silica gel column chromatography (n-hexane:EtOAc ¼ 2:1
ꢀ1:1) to afford 14 (290 mg, 99%) as a powder; [a]D 22.08 (c 0.7, CH2Cl2); mp:
215 ꢀ 2178C (recrystalized from EtOAc and n-hexane); 1H-NMR (CDCl3) d
8.05–7.81 and 7.58–7.25 (m, 20H, phenyl), 5.91 (dd, 1H, H-30, J ¼ 9.5,
9.5 Hz), 5.67 (dd, 1H, H-40, J ¼ 9.5, 9.5 Hz), 5.52 (dd, 1H, H-20, J ¼ 8.1,
9.5 Hz), 4.97 (d, 1H, H-10, J ¼ 8.1 Hz), 4.69 (dd, 1H, H-60a, J ¼ 2.9, 12.1 Hz),
4.68–4.64 (m, 1H, H-3), 4.49 (dd, 1H, H-60b, J ¼ 5.1, 12.1 Hz), 4.33 (dd,
1H, H-4a, J ¼ 5.5, 10.6 Hz), 4.23 (dd, 1H, H-4b, J ¼ 2.6, 10.6 Hz), 4.17 (ddd,
1H, H-5, J ¼ 2.9, 5.1, 9.5 Hz), 2.77 (dd, 1H, H-2a, J ¼ 3.3, 18.3 Hz), 2.71,
(dd, 1H, H-2b, J ¼ 6.2, 18.3 Hz); 13C-NMR (CDCl3) d 174.73 (C-1), 165.99,
165.70, 165.11, 164.95, 133.53, 133.43, 133.33, 133.30, 129.79–128.29, 100.29
(C-10), 74.19 (C-3), 72.87, 72.61, 72.47 (C-30, 50, 4), 71.28 (C-20), 69.32 (C-40),
62.72 (C-60), 35.68 (C-2). Anal. Calcd for C38H32O12: C, 67.05; H, 4.74. Found:
C, 67.29; H, 4.75.
ACKNOWLEDGMENT
This work was supported in part by a grant for the High-Technology Research
Center of Iwaki Meisei University from the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
REFERENCES
[1] Kan, W.S. Pharmaceutical Botany; National Research Institute of Chinese
Medicine: Taiwan, 1986; 647.
[2] Sun, Z.C. The Herbs. In Harvest Farm Magazine; Taiwan, 1987; 57–58.
[3] Ito, A.; Kasai, R.; Yamasaki, K.; Sugimoto, H. Aliphatic and aromatic glucosides
from Anoectochilus Koshunesis. Phytochemistry 1993, 33, 1133–1137.
[4] Takatsuki, S.; Wang, J.D.; Narui, T.; Okuyama, T. Studies on the components of
crude drug “Kim-soan-lian.” J. Jap. Botany 1992, 67, 121–123.
[5] Du, X.M.; Yoshizawa, T.; Syoyama, Y. Butanoic acid glucoside composition of whole
body and in vitro plantlets of Anoectochilus formosanus. Phytochemistry 1998, 49,
1925–1928.
[6] Lin, C.C.; Namba, T. Pharmacognostical studies on the crude drugs of orchidaceae
from Taiwan (IV) on “Kim-soan-lian” (1). Shoyakukagaku Zasshi 1981, 35 (4),
262–271.
[7] Schmidt, R.R. New methods for the synthesis of glycosides and oligosaccharides—
Are there alternatives to the Koenigs-Knorr method? Angew. Chem. 1986, 98,
213–236; Angew. Chem. Int. Ed. Engl. 1986, 25, 212–235.

LCAR50541
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K. Suzuki et al.
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[8] Ogawa, T.; Nakabayashi, S. Synthesis of a hexasaccharide unit of a complex type of
glycan chain of a glycoprotein. Carbohydr. Res. 1981, 93, C1–C5.
[9] Carlsen, P.H.J.; Katsuki, T.; Martin, V.S.; Sharpless, K.B. A greatly improved pro-
cedure for ruthenium tetraoxide catalyzed oxidations of organic compounds. J. Org.
Chem. 1981, 46, 3936–3938.
[10] Du, X.M.; Sun, N.Y.; Chen, Y.; Irino, N.; Syoyama, Y. Hepatoprotective aliphatic
glycosides from three Goodyera species. Biol. Pharm. Bull. 2000, 23 (6),
731–734. received/accepted dates for your manuscript.