A simple synthesis of four stereoisomers of roseoside and their inhibitory activity on leukotriene release from mice bone marrow-derived cultured mast cells

Article abstract of DOI:10.1016/j.bmc.2008.11.002

Four stereoisomers of roseoside (vomifoliol glucosides) were synthesized using glucose as a chiral resolving reagent. The four synthetic stereoisomers exhibited inhibitory activity on leukotriene release from mouse bone marrow-derived cultured mast cells (BMCMC). The (6S)-isomers of roseoside were about twice as active as (6R)-isomers.

Full text of DOI:10.1016/j.bmc.2008.11.002

Bioorganic & Medicinal Chemistry 17 (2009) 189–194
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Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
A simple synthesis of four stereoisomers of roseoside and their inhibitory
activity on leukotriene release from mice bone marrow-derived
cultured mast cells
a
b
a
a
Arata Yajima a, , Yutaka Oono , Ryusuke Nakagawa , Tomoo Nukada , Goro Yabuta
*
a Department of Fermentation Science, Faculty of Applied Biological Science, Tokyo University of Agriculture (NODAI), Sakuragaoka 1-1-1, Setagaya-ku, Tokyo 156-8502, Japan
b Mercian Cleantec Co. Ltd., Jyonan 4-9-1, Fujisawa-shi, Kanagawa 251-0057, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Four stereoisomers of roseoside (vomifoliol glucosides) were synthesized using glucose as a chiral resolv-
ing reagent. The four synthetic stereoisomers exhibited inhibitory activity on leukotriene release from
mouse bone marrow-derived cultured mast cells (BMCMC). The (6S)-isomers of roseoside were about
twice as active as (6R)-isomers.
Received 21 October 2008
Revised 4 November 2008
Accepted 4 November 2008
Available online 8 November 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Roseoside
Corchoionoside C
Histamine release inhibitor
Leukotriene
1. Introduction
The tropical plant Corchorus olitorius L. (Tiliaceae), known as
‘moroheiya’ in Japanese, is used as a vegetable and is rich in vita-
mins and carotenoids. During a course of studies on the bioactive
principles of medicinal foodstuffs, Yoshikawa and co-workers iso-
lated corchoionosides A (1), B (2) and C [=(6S,9S)-roseoside (3)],
and (6S,9R)-roseoside (4) from the leaves of Vietnamese C. olitorius
L. (Fig. 1).1 Corchoionosides A (1) and B (2), and (6S,9R)-roseoside
(4) were found to exhibit inhibitory activity on the release of his-
tamine from rat peritoneal exudate cells induced by an antigen–
antibody reaction. However, the anti-histamine-release activites
of corchoionoside C (3) and the (6R)-isomers of roseoside are
unknown. Roseosides may be biosynthesized by oxidative cleavage
of carotenoids, and 6S-isomer is the most commonly found among
natural sources.2 The only exception is (6R,9R)-roseoside (5), iso-
lated from Alangium premnifolium by Otsuka.2h Although roseo-
sides have been isolated from
a wide variety of natural
sources,1,2 their biological functions and activities are unclear. In
order to examine the anti-allergy activity of roseoside stereoiso-
mers 3, 4, 5 and 6, we investigated the synthesis of these four
stereoisomers.
Figure 1. Structures of corchoionosides, roseosides and spionosides.
2. Results and discussion
Recently, Yamano and Ito reported the synthesis of four roseo-
side stereoisomers.3 Their synthesis began with a chiral cyclohex-
anone derivative, and involved 19 steps via asymmetric transfer
hydrogenation to construct the C-9 asymmetric center. We chose
* Corresponding author. Tel.: +81 3 5477 2264; fax: +81 3 5477 2622.
E-mail address: ayaji@nodai.ac.jp (A. Yajima).
0968-0896/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2008.11.002

190
A. Yajima et al. / Bioorg. Med. Chem. 17 (2009) 189–194
a different route for roseoside synthesis, which is summarized in
Scheme 1. As the synthesis of the four stereoisomers was urgently
required to allow investigation of the stereochemistry–biological
activity relationship, we planned to separate each stereoisomer
from a diastereomeric mixture. To construct the C-6 stereogenic
center, the 1,2-addition of organo-metal reagent C to cyclohexe-
none B leads to a diastereomeric mixture of A, and the resulting
diastereomers can be separated. Our plan was to resolve racemic
and the ethylene acetal groups of 16, the diastereoselectivity of the
segment coupling reaction was estimated to be approximately
55:45 by HPLC and 1H NMR analysis regardless of the absolute con-
figuration at the C-20 position of 14. This means that the slight dia-
stereo induction observed (55:45) is due to the stereochemistry of
the sugar moiety. Although it was impossible to determine the
absolute configuration of each deprotected product, the isomers
at the C-6 position of 17 were separable by MPLC for 9S isomers
and preparative HPLC for 9R isomers. Deprotection of the acetonide
group of the separated stereoisomers of 17 gave the four roseoside
3-butyn-2-ol (E) by employing inexpensive D-glucose (D) as a chi-
ral resolving agent and to separate the diastereomeric glucoside.
Thus, commercially available 4-ketoisopholone, 3-butyn-2-ol and
stereoisomers 3, 4, 5 and 6, whose physical properties such as [a]
D
D-glucose were selected as the starting materials. This strategy
values and 1H and 13C NMR spectra were in good accordance with
the reported data.1,2 The absolute configuration at C-6 generated
by the segment coupling was determined by a comparison of the
was also expected to provide a method for the synthesis of spion-
osides A (7) and B (8) (Fig. 1), related natural products isolated
from Capparis spinosa fruits.2l
[a] values of the synthetic products with those of the reported
D
Scheme 2 summarizes the synthesis of the key intermediate 14.
Glucosidation of ( )-9, catalyzed by silver trifluoromethanesulfo-
nate (AgOTf), proceeded smoothly in the presence of silver carbon-
ate4 at –20 °C. Although the resulting b-glucoside 115 was a
data. Based on these stereochemical assignments, the (6S)-isomers
were concluded to be the preferred isomers in the 1,2-addition
reactions.
Next, the biological activites of the four stereoisomers of roseo-
side were compared based on an inhibition assay of leukotriene re-
lease from mouse bone marrow-derived cultured mast cells
(BMCMC).8 In this study we chose to employ a simpler anti-leuko-
triene release assay rather than an anti-histamine release assay.
Table 1 shows the rate of inhibition of leukotriene release from
BMCMC using 100 mM of roseoside, as measured by a commer-
cially available CAST ELISA kit. The (6S)-isomers (3 and 4) were
found to be about twice as active as the (6R)-isomers (5 and 6).
diastereomeric mixture at C-20 (1:1), the corresponding
a-gluco-
side was not observed in 1H NMR analysis. The acetyl groups of
11 were removed by treatment with KCN in MeOH6 to give 12. Pro-
tection of the 4- and 6-hydroxy groups as an isopropylidene acetal
(13) and the 2- and 3-hydroxy groups as a tetraisopropyldisilox-
anilidene (TIPDS) acetal gave 14. Fortunately, the C-20 diastereo-
mers of 14 were easily separated by silica gel column
chromatography at this stage to give (20R)-14 and (20S)-14, respec-
tively. The absolute configuration at C-20 was confirmed by the
comparison of the 1H NMR spectra of both isomers with that of
an authentic sample which was synthesized by using optically ac-
tive 3-butyn-2-ol[(S)-9] as a starting material. A b-glucosidation
reaction with 1.2 equivalent of (S)-9 under the same conditions
gave (20S)-11 in slightly lowered yield (71%), and (20S)-14 was syn-
thesized in three steps by the method as described above (53%).
As shown in Scheme 3, segment coupling between 157 and the
lithium acetylide of 14, and reduction of the triple bond with Red-
Al, yielded the desired allyl alcohol 16. After deprotection of TIPDS
3. Conclusion
A simple and practical synthesis of the four stereoisomers of
roseoside, 3, 4, 5 and 6, was achieved. The overall yield of the four
roseoside stereoisomers was 10–13% for 10 synthetic steps from D-
glucose. By using 14 as a common intermediate, related natural
products such as spionosides A (7) and B (8),2l isolated from C. spin-
osa, would also be synthesized in similar manners. An anti-leuko-
triene release assay of the four roseoside stereoisomers gave
interesting results that the (6S)-isomers were about twice as active
as the (6R)-isomers. This result indicates that the structure of
cyclohexenone portion of roseoside is important in its activity. Be-
cause most of naturally occurring roseosides have 6S configuration,
natural food sources containing roseosides could act as functional
foods with anti-allergy activity.
4. Experimental
4.1. General
Optical rotations were recorded by JASCO DIP-140. IR spectra
were measured with a Shimadzu IR-4100 spectrometer. NMR spec-
Scheme 1. Retrosynthetic analysis of roseosides.
Scheme 2. Synthesis of the key intermediates (20R)- and (20S)-14. Reagents, conditions and yields: (a) ( )-9, AgOTf, Ag2CO3, CH2Cl2, MS 4A, –20 °C to r.t. (80%); (b) KCN, MeOH,
55 °C (quant.); (c) dimethoxypropane, PPTS, THF (87%); (d) TIPDSCl2, imidazole, THF; (e) SiO2 chromatog. [44% for (20R)-14 and 44% for (20S)-14]; (f) (–)-9, AgOTf, Ag2CO3,
CH2Cl2, MS 4A, –20 °C to r.t. (71%).

A. Yajima et al. / Bioorg. Med. Chem. 17 (2009) 189–194
191
Scheme 3. Synthesis of the four stereoisomers of roseoside. Reagents, conditions and yields: (a) n-BuLi, THF, –78 °C, then 15 [94% for (20S)-isomer and 97% for (20R)-isomer];
(b) Red-Al, THF, –10 °C to r.t. [86% for (20S)-16 and 74% for (20R)-16]; (c) TBAF, THF, H2O then AcOH, Et2O, H2O [quant. for (20S)-17 and 94% for (20R)-17]; (d) MPLC separation;
(e) HPLC separation; (f) PPTS, EtOH, H2O [quant. for (6S,90S)-3, 99% for (6R,90S)-5, 99% for (6S,90R)-4 and 96% for (6R,90R)-6].
(c = 1.0, CHCl3); IR (film): tmax (cmꢀ1) = 3279 (s), 2943 (s), 2112
Table 1
(w), 1739 (s), 1233 (s), 1159 (s), 1051 (s). 1H NMR (CDCl3,
Inhibitory effects of the roseoside four stereoisomers (100 mM) on leukotriene release
from BMCMC (means S.E., n = 3)
400 MHz): d = 1.46 (d, J = 6.8 Hz, 3H), 2.00–2.10 (m, 12H), 2.46,
2.50 (d, J = 2.4 Hz, 1H), 3.73 (ddd, J = 2.4, 5.4, 9.3 Hz, 1H), 4.13 (dd,
J = 2.4, 12.2 Hz, 1H), 4.26 (dd, J = 5.4, 12.2 Hz, 1H), 4.54 (dq, J = 2.4,
6.8 Hz, 1 H), 4.77, 4.85 (d, J = 7.8 Hz, 1H), 4.99 (dd, J = 7.8, 9.8 Hz,
1H), 5.08 (dd, J = 9.3, 9.8 Hz, 1H), 5.22 (dd, J = 9.3, 9.3 Hz, 1H). Found:
C, 54.01%, H, 6.01%. Calcd for C18H24O10: C, 53.99%, H, 6.04%.
Inhibition rate (%)
(6S,9S)-3
(6S,9R)-4
(6R,9S)-5
(6R,9R)-6
70.3 7.5
67.4 6.3
36.7 8.4
22.9 12.3
4.1.2. (20S)-30-Butyn-20-yl-(2,3,4,6-tetra-O-acetyl)-b-
D-
tra were recorded with a Jeol JNM-A400 spectrometer operating at
400 MHz for the 1H NMR spectra and at 100 MHz for 13C NMR
spectra. Chemical shifts are reported as ppm relative to CHCl3 or
CH3OH measured from the solvent resonance (1H NMR; CHCl3:
7.26 ppm or CH3OH: 3.30 ppm, 13C NMR; CDCl3: 77.0 ppm or
CD3OD: 49.0 ppm). The elemental compositions were analyzed
on a J-Science MICROCORDER JM10. Column chromatography
was carried out with silica gel (Wakogel C-200). Medium pressure
chromatography was carried out with silica gel (Wakogel C-500
HG) and YAMAZEN YFLC-600A as a pump. Preparative HPLC was
carried out with Develosil 30-5 as a column and Shimadzu LC-
6AD as a pump.
glucopyranoside (11)
(20S)-11 was prepared from 10 and 1.2 eq. of (S)-9 in the same
22
manner just as described above (71%). [
a]
–47.6 (c = 1.00,
D
CHCl3); IR (film): tmax (cmꢀ1) = 3279 (s), 2943 (s), 2112 (w), 1739
(s), 1233 (s), 1159 (s), 1051 (s). 1H NMR (CDCl3, 400 MHz):
d = 1.44 (d, J = 6.8 Hz, 3H), 2.00, 2.02, 2.05 and 2.08 (s ꢁ 4, 12 H),
2.46 (d, J = 2.4 Hz, 1H), 3.73 (ddd, J = 2.4, 5.4, 9.3 Hz, 1H), 4.13
(dd, J = 2.4, 12.2 Hz, 1H), 4.26 (dd, J = 5.4, 12.2 Hz, 1H), 4.59 (dq,
J = 2.4, 6.8 Hz, 1H), 4.77 (d, J = 7.8 Hz, 1H), 4.99 (dd, J = 7.8,
9.3 Hz, 1H), 5.08 (dd, J = 9.3, 9.3 Hz, 1H), 5.24 (dd, J = 9.3, 9.3 Hz,
1H). Found: C, 53.99%, H, 6.04%. Calcd for C18H24O10: C, 53.99%,
H, 6.04%.
4.1.1. (20RS)-30-Butyn-20-yl-(2,3,4,6-tetra-O-acetyl)-b-
D-
glucopyranoside (11)
Powdered MS 4A (6 g) was dried at 140 °C under reduced pres-
sure for 1 day in a two necked flask. To the flask were added dry sil-
ver carbonate (2.53 g, 9.17 mmol) prepared by azeotoropic removal
of water with toluene, silver trifluoromethanesulfonate (222 mg,
4.1.3. (20RS)-30-Butyn-20-yl-b-
D-glucopyranoside (12)
To a stirred solution of (20RS)-11 (2.35 g, 5.87 mmol) in MeOH
(50 ml) was added KCN (191 mg, 2.93 mmol) at 55 °C. The mixture
was stirred for 3 h and the solvent was removed by evaporation.
The residue was chromatographed on silica gel (45 g, CHCl3/
MeOH = 5:1) to give 1.36 g of (20RS)-12 (quant.) as a colorless
860 lmol) and dry CH2Cl2 (30 ml) under Ar atmosphere. After cool-
22
amorphous solid. [
a]
D
–13.1 (c = 1.0, MeOH); IR (film): tmax
ing to –15 °C, freshly distilled ( )-3-butyn-2-ol (9, 1.57 ml,
20.0 mmol) was added, and the mixture was stirred for 30 min. To
the mixture was added the solution of bromide (10, 1.17 g,
2.85 mmol) in dry CH2Cl2. The reaction mixture was allowed to
warm to room temperature, and stirred for 1 day. The mixture was
filtered through a Celite pad, and the filtrate was washed with sat.
NaHCO3 aq. The aqueous phase was extracted with CHCl3 and the
combined organic phase was washed with brine and dried over
MgSO4. The solvent was evaporated, and the residue was purified
by column chromatography with hexane/EtOAc (2:1) to give
(cmꢀ1) = 3405 (br.s, OH), 3279 (w), 2934 (m), 2112 (w), 1079 (s).
1 H NMR (CD3OD, 400 MHz): d = 1.41, 1.44 (d, J = 6.8 Hz, 3H),
2.84, 2.86 (d, J = 2.4 Hz, 1H), 3.18 (m, 1H), 3.23–3.39 (m, 3H),
3.61–3.68 (m, 1H), 3.86–3.92 (m, 1H), 4.41, 4.68 (d, J = 7.8 Hz,
1H), 4.62, 4.75 (dq, J = 2.4, 6.8 Hz, 1H). Found: C, 51.74%, H,
6.95%. Calcd for C10H16O6: C, 51.72%, H, 6.94%.
4.1.4. (20S)-30-Butyn-20-yl-b-
D-glucopyranoside (12)
In the same manner just as described above, (20S)-12 was pre-
22
(20RS)-11 (911 mg, 80%) as a colorless amorphous solid. [
a
]
D
22 +2.8
pared from (20S)-11 (91%). [
a
]
D
–194.1 (c = 1.20, MeOH); IR

192
A. Yajima et al. / Bioorg. Med. Chem. 17 (2009) 189–194
(film):
t
max (cmꢀ1) = 3405 (br.s, OH), 3279 (w), 2934 (m), 2112 (w),
(ddd, J = 5.4, 9.8, 10.7 Hz, 1H), 3.52 (m, 2H), 3.69 (dd, J = 8.3,
8.8 Hz, 1H), 3.76 (dd, J = 10.3, 10.7 Hz, 1H), 3.91 (dd, J = 5.4,
10.7 Hz, 1H), 4.60 (dq, J = 2.0, 6.3 Hz, 1H), 4.70 (d, J = 7.8 Hz, 1H).
13C NMR (CDCl3, 100 MHz): d = 12.1, 12.8 (ꢁ2), 16.9, 17.0 (ꢁ2),
17.2, 17.3 (ꢁ2), 18.9, 22.0, 29.0, 62.2, 63.4, 66.9, 71.3, 73.1, 73.3,
74.4, 75.4, 77.1, 80.5, 82.8, 99.9, 100.6. Found: C, 58.32%, H,
9.01%. Calcd for C25H46O7Si2: C, 58.32%, H, 9.01%.
1079 (s). 1H NMR (CD3OD, 400 MHz): d = 1.44 (d, J = 6.3 Hz, 3H),
2.86 (d, J = 2.4 Hz, 1H), 3.18 (dd, J = 7.8, 7.8 Hz, 1H), 3.25–3.39
(m, 3H), 3.64 (m, 1H), 3.90 (dd, J = 1.4, 11.7 Hz, 1 H), 4.60 (d,
J = 7.8 Hz, 1H), 4.75 (dq, J = 2.4, 6.8 Hz, 1H). Found: C, 51.57%, H,
6.69%. Calcd for C10H16O6: C, 51.72%, H, 6.94%.
4.1.5. (20RS)-30-Butyn-20-yl-(4,6-O-isopropylidene)-b-
D-
glucopyranoside (13)
4.1.8. (100RS,20R)-40-(400,400-Ethylenedioxy-100-hydroxy-200,600,600-
trimethyl-200-cyclohexen-100-yl)-30-butyn-20-yl-[2,3-O-(tetraiso-
To a stirred solution of (20RS)-12 (174 mg, 768
lmol) in dry THF
(5 ml) were added 2,2-dimethoxypropane (4.00 ml, 32.6 mmol)
and a catalytic amount (ca. 10 mg) of pyridinium p-toluenesulfo-
nate at 0 °C under Ar. The solution was stirred for 1 day at room
temperature and the reaction was quenched with Et3N. The solu-
tion was concentrated in vacuo, and the residue was purified by
column chromatography (6 g, CHCl3) to give 177 mg of (20RS)-13
propyldisiloxane-1,3-diyl)-4,6-O-isopropylidene]-b-D-glucopyr-
anoside
To a stirred solution of (20R)-14 (726 mg, 1.41 mmol) in dry THF
was added slowly 1.60 M n-BuLi in hexane (1.06 ml, 1.69 mmol) at
–78 °C under Ar. After stirring for 20 min, a solution of 15 (332 mg,
1.69 mmol) in dry THF (10 ml) was added dropwise to the mixture.
The reaction mixture was allowed to warm to room temperature
and stirred for 5 h. The mixture was poured into water and the
aqueous phase was extracted with EtOAc. The combined organic
phases were washed with brine and dried with Na2SO4. After con-
centration in vacuo, the residue was chromatographed on silica gel
(87%) as a colorless amorphous solid and the recovered starting
22
material (20RS)-12 (14 mg, 8%). [
a
]
D
–0.3 (c = 1.0, MeOH); IR
(film): tmax (cmꢀ1) = 3435 (br.s, OH), 2993 (s), 2889 (s), 2112 (s),
1267–1010 (s). 1H NMR (CDCl3, 400 MHz): d = 1.44 (s, 3H), 1.49–
1.51 (m, 6H), 2.49, 2.51 (d, J = 2.0 Hz, 1H), 2.62 (br.s, 1H), 2.83
(br.s, 1H), 3.24–3.32 (m, 1H), 3.42–3.92 (m, 5H), 4.54, 4.70 (d,
J = 7.8 Hz, 1H), 4.58, 4.63 (dq, J = 2.0, 6.8 Hz, 1H). Found: C,
57.33%, H, 7.40%. Calcd for C13H20O6: C, 57.34%, H, 7.40%.
(35 g, hexane/EtOAc = 10:1) to give 947 mg (94%) of the title com-
23
pound as a colorless amorphous solid. [
a]
–10.1 (c = 0.98,
D
CHCl3). IR (film):
t
max = 3448 cm-1 (br.m, OH), 2946–2869 (s),
1092 (s), 834 (s). 1H NMR (CDCl3, 400 MHz): d = 0.95–1.09 (m,
34 H), 1.13, 1.14 (s, 2H), 1.37 (s, 3H), 1.44 (d, J = 1.0 Hz, 3H), 1.45
(s, 3H), 1.89, 1.90 (d, J = 1.0 Hz, 3H), 3.10, 3.24 (ddd, J = 5.4, 9.8,
10.2 Hz, 1H), 3.45–3.54 (m, 2H), 3.65, 3.66 (dd, J = 8.3, 8.8 Hz,
1 H), 3.75 (dd, J = 10.2, 10.7 Hz, 1H), 3.89–3.97 (m, 5H), 4.50–4.55
(m, 2H), 5.36 (br.s, 1H). 13C NMR (CDCl3, 100 MHz): d = 12.0,
12.2, 12.8, 12.9, 16.9, 17.1, 17.2, 17.3, 17.4, 19.0, 22.0, 22.1 (ꢁ2),
22.7, 22.8, 25.1, 25.4, 25.5, 29.0, 39.2, 43.4, 62.3, 63.7, 64.1, 64.2,
67.1, 67.2, 67.5, 72.8, 72.9, 74.3, 78.1, 85.1, 85.7, 85.8, 99.2,
102.9, 103.0, 104.8, 123.4, 123.5, 126.2, 140.0, 140.1. Found: C,
60.81%, H, 8.79%. Calcd for C36H62O10Si2: C, 60.81%, H, 8.79%.
4.1.6. (20S)-30-Butyn-20-yl-(4,6-O-isopropylidene)-b-
D-
glucopyranoside (13)
In the same manner just as described above, (20S)-13 was pre-
22
pared from (20S)-12 (70%). [
a]
–72.7 (c = 0.60, CHCl3). IR (film):
D
tmax (cmꢀ1) = 3435 (br.s, OH), 2993 (s), 2889 (s), 2112 (s), 1267–
1010 (s). 1H NMR (CDCl3, 400 MHz): d = 1.44 (s, 3H), 1.50 (d,
J = 6.3 Hz, 3H), 1.51 (s, 3 H), 1.56 (s, 3H), 2.45 (d, J = 2.0 Hz, 1H),
2.49 (d, J = 2.0 Hz, 1H), 2.60 (d, J = 2.0 Hz, 1H), 3.32 (ddd, J = 5.4,
10.8, 10.8 Hz, 1H), 3.48 (m, 1 H), 3.60 (dd, J = 9.2, 9.2 Hz, 1H),
3.73 (ddd, J = 2.0, 10.8, 10.8 Hz, 1H), 3.79 (dd, J = 10.8, 10.8 Hz,
1H), 3.93 (dd, J = 5.4, 10.8 Hz, 1H), 4.63 (dq, J = 2.0, 6.8 Hz, 1H),
4.70 (d, J = 7.8 Hz, 1H). Found: C, 57.53%, H, 7.62%. Calcd for
C13H20O6: C, 57.34%, H, 7.40%.
4.1.9. (1”RS,20S)-40-(400,400-Ethylenedioxy-100-hydroxy-200,600,600-
trimethyl-200-cyclohexen-100-yl)-30-butyn-20-yl-[2,3-O-
(tetraisopropyldisiloxane-1,3-diyl)-4,6-O-isopropylidene]-b-D-
4.1.7. (20R)- and (20S)-30-Butyn-20-yl-[2,3-O-(tetraisopropyldisil-
glucopyranoside
oxane-1,3-diyl)-4,6-O-isopropylidene]-b-
D
-glucopyranoside (14)
In the same manner just as described above, (100RS,20S)-isomer
was prepared from 1.29 g (2.51 mmol) of (20S)-14 to give 1.73 g
To a stirred solution of (20RS)-13 (1.97 g, 7.23 mmol) and imid-
azole (2.22 g, 32.6 mmol) in dry THF (45 ml) was added 1,3-dich-
rolo-1,1,3,3-tetraisopropyldisiloxane (2.78 ml, 8.68 mmol) at 0 °C
under Ar. The reaction mixture was stirred for 12 h at room tem-
perature and the mixture was poured into water. The aqueous
phase was extracted with ether and the combined organic phases
were washed with brine and dried with Na2SO4. After concentra-
tion in vacuo, the residue was chromatographed on silica gel
(120 g, hexane/EtOAc = 190:1) to give 1.62 g (44%) of (20R)-14
(97%) of the title compound as a colorless amorphous solid.
23
[a]
–60.9 (c = 0.13, CHCl3). IR (film): t
max = 3466 cmꢀ1 (br.w,
D
OH), 2946–2869 (s), 1093 (s), 834 (s). 1H NMR (CDCl3, 400 MHz):
d = 0.94–1.10 (m, 34H), 1.13, 1.14 (s, 2H), 1.38 (s, 3H), 1.42, 1.44
(d, J = 2.0 Hz, 3H), 1.46 (s, 3H), 1.90 (br.d, J = 1.5 Hz, 3H), 3.25 (m,
1H), 3.52 (t, J = 7.8 Hz, 1H), 3.53 (dd, J = 9.3, 9.8 Hz, 1H), 3.68 (m,
1H), 3.75 (br.t, J = 10.7 Hz, 1H), 3.90–3.97 (m, 5H), 4.67–4.71 (m,
2H), 5.37 (br.s, 1H). 13C NMR (CDCl3, 100 MHz): d = 11.9, 12.2,
12.7, 12.8, 16.9, 17.1, 17.3, 17.4, 19.0, 22.0, 22.8, 25.2, 25.5, 29.0,
39.1, 41.7, 43.5, 62.2, 62.3, 62.9, 63.0, 63.7, 64.1, 64.3, 66.8, 66.9,
67.1, 73.1, 73.2, 74.4, 84.8, 86.1, 99.2, 99.3, 100.1, 100.4, 104.7,
123.5, 126.3, 140.02, 140.13. Found: C, 60.81%, H, 8.80%. Calcd for
C36H62O10Si2: C, 60.81%, H, 8.79%.
and 1.63 g (44%) of (20S)-14 as colorless solids.
22
Properties of (20R)-isomer: [
a]
–13.4 (c = 0.98, CHCl3). IR
D
(film): t
max = 3256 cmꢀ1 (s), 2945–2867 (s), 2122 (s), 1090 (s). 1H
NMR (CDCl3, 400 MHz): d = 0.87–1.11 (m, 28H), 1.37 (s, 3H), 1.45
(s, 3H), 1.46 (d, J = 6.8 Hz, 3 H), 2.44 (d, J = 2.4 Hz, 1H), 3.25 (ddd,
J = 5.4, 9.8, 10.3 Hz, 1H), 3.54 (m, 2H), 3.66 (dd, J = 7.8, 8.8 Hz,
1H), 3.79 (dd, J = 10.3, 10.7 Hz, 1H), 3.93 (dd, J = 5.4, 10.7 Hz, 1H),
4.49 (dq, J = 2.4, 6.8 Hz, 1H), 4.52 (d, J = 7.8 Hz, 1H). 13C NMR
(CDCl3, 100 MHz): d = 12.2, 12.8, 12.9, 16.9, 17.1 (ꢁ2), 17.2 (ꢁ2),
17.3, 19.0, 22.1, 29.0, 62.3, 66.5, 67.4, 71.3, 72.9, 73.0, 74.8, 76.0,
77.9, 80.5, 83.5, 99.3, 102.9. Found: C, 58.30%, H, 9.00%. Calcd for
4.1.10. (100RS,20R,30E)-40-(400,400-Ethylenedioxy-100-hydroxy-
200,600,600-trimethyl-200-cyclohexen-100-yl)-300-buten-20-yl-[2,3-O-
(tetraisopropyldisiloxane-1,3-diyl)-4,6-O-isopropylidene]-b-
D-
glucopyranoside [(100RS,20R,30E)-16]
To a stirred solution of (100RS,20R)-isomer of the above com-
pound (2.20 g, 3.09 mmol) in dry THF (40 ml) was added a solution
of 65 wt% Red-Al in toluene (2.79 ml, 9.30 mmol), diluted with dry
THF (10 ml), at 0 °C under Ar. After stirring for 4 h, the reaction was
quenched with careful addition of water and saturated Rochelle
salt solution. The mixture was stirred for 30 min at room temper-
C25H46O7Si2: C, 58.32%, H, 9.01%.
22
Properties of (20S)-isomer: [
a
]
–71.7 (c = 1.00, CHCl3). IR
D
(film): t
max = 3311 cmꢀ1 (s), 2992–2869 (s), 2134 (w), 1091 (s).
1H NMR (CDCl3, 400 MHz): d = 1.01–1.08 (m, 28H), 1.37 (s, 3H),
1.45 (d, J = 6.3 Hz, 3H), 1.46 (s, 3H), 2.38 (d, J = 2.0 Hz, 1H), 3.25

A. Yajima et al. / Bioorg. Med. Chem. 17 (2009) 189–194
193
22
ature and the aqueous phase was extracted with EtOAc. The com-
bined organic phase was washed with brine and dried with
Na2SO4. After concentration in vacuo, the residue was chromato-
Properties of (6S,9R)-isomer: Colorless amorphous solid, [
+80.9 (c = 1.07, CHCl3). IR (film):
a]
D
t
max = 3503 cmꢀ1 (br.m, OH),
2947–2869 (s), 1670 (w), 1092 (s), 834 (s). 1H NMR (CDCl3,
400 MHz): d = 1.01 (s, 3H), 1.08 (s, 3H) 1.31 (d, J = 6.3 Hz, 3H),
1.43 (s, 3H), 1.50 (s, 3H), 1.88 (d, J = 1.0 Hz, 3H), 2.24 (d,
J = 16.6 Hz, 1H), 2.41 (d, J = 16.6 Hz, 1H), 3.22 (ddd, J = 5.4, 9.8,
10.3 Hz, 1H), 3.45 (dd, J = 7.8, 8.8 Hz, 1H), 3.57 (dd, J = 9.3, 9.8 Hz,
1H), 3.66 (dd, J = 8.8, 9.3 Hz, 1H), 3.75 (dd, J = 10.3, 10.7 Hz, 1H),
3.83 (dd, J = 5.4, 10.7 Hz, 1H), 4.34 (sep, J = 6.3 Hz, 1H), 4.40 (d,
J = 7.8 Hz, 1H), 5.75 (d, J = 15.6 Hz, 1H), 5.83 (dd, J = 6.3, 15.6 Hz,
1H), 5.91 (br.s, 1H). 13C NMR (CDCl3, 100 MHz): d = 18.9, 19.0,
21.2, 22.8, 24.1, 29.0, 30.9, 41.2, 49.6, 62.0, 65.9, 67.4, 73.0, 73.5,
74.6, 99.8, 102.1, 127.1, 130.3, 133.6162.2, 197.8. Found: C,
graphed on silica gel (77 g, hexane/EtOAc = 10:1) to give 1.89 g
23
(86%) of 16 as a colorless amorphous solid. [
a
]
D
–60 (c = 0.08,
CHCl3). IR (film):
t
max = 3504 cm-1 (br.m, OH), 2946–2869 (s),
1670 (w), 1091 (s). 1H NMR (CDCl3, 400 MHz): d = 0.86–1.08 (m,
34H), 1.25, 1.27 (d, J = 2.0 Hz, 3H), 1.36 (s, 3H), 1.44 (s, 3H), 1.64,
1.67 (d, J = 1.5 Hz, 3 H), 1.70 (dd, J = 1.5, 14.2 Hz, 1H), 1.88, 1.90
(br.d, J = 14.2 Hz, 1H), 3.13 (m, 1H), 3.47–3.53 (m, 2H), 3.63 (dd,
J = 8.3, 8.8 Hz, 1H), 3.72 (m, 1H), 3.84–4.02 (m, 5H), 4.23 (m, 1H),
4.33, 4.34 (d, J = 7.8 Hz, 1H), 5.40 (m, 1H), 5.64, 5.65 (d,
J = 15.6 Hz, 1H), 5.72, 5.74 (dd, J = 2.4, 15.6 Hz, 1H). 13C NMR
(CDCl3, 100 MHz): d = 12.1, 12.2, 12.3, 12.9, 16.9, 17.1, 17.2, 17.4,
17.9, 18.0, 18.8, 19.0, 21.3, 21.5, 22.8, 23.1, 24.1, 24.8, 28.9, 38.6,
41.1, 44.7, 49.7, 62.3, 63.7, 63.9, 64.5, 67.3, 72.9, 73.0, 77.8, 78.2,
78.4, 99.2, 99.3, 102.4, 102.8, 104.9, 123.7, 126.9, 127.0, 130.1,
132.5, 132.6, 133.7, 133.8, 141.7. Found: C, 60.63%, H, 9.05%. Calcd
for C36H64O10Si2: C, 60.63%, H, 9.05%.
61.95%, H, 8.04%. Calcd for C22H34O8: C, 61.95%, H, 8.04%.
Properties of (6R,9R)-isomer: Colorless amorphous solid, [
125.0 (c = 1.03, CHCl3). IR (film):
22
a
]
–
D
t
max = 3503 cmꢀ1 (br.m, OH),
2947–2869 (s), 1670 (w), 1092 (s), 834 (s). 1H NMR (CDCl3,
400 MHz): d = 0.99 (s, 3H), 1.07 (s, 3 H), 1.32 (d, J = 6.4 Hz, 3H),
1.43 (s, 3H), 1.50 (s, 3H), 1.89 (d, J = 1.5 Hz, 3H), 2.23 (d, J = 17.1
Hz, 1H), 2.44 (d, J = 17.1 Hz, 1H), 3.21 (ddd, J = 5.4, 9.3, 10.3 Hz,
1H), 3.43 (dd, J = 7.8, 8.8 Hz, 1H), 3.56 (t, J = 9.3 Hz, 1H), 3.65 (dd,
J = 8.8, 9.3 Hz, 1H), 3.74 (dd, J = 10.3, 10.7 Hz, 1H), 3.83 (dd,
J = 5.4, 10.7 Hz, 1H), 4.34 (sep, J = 6.4 Hz, 1H), 4.39 (d, J = 7.8 Hz,
1H), 5.75 (d, J = 15.6 Hz, 1H), 5.83 (dd, J = 6.4, 15.6 Hz, 1H), 5.60
(d, J = 1.5 Hz, 1H). 13C NMR (CDCl3, 100 MHz): d = 19.0, 19.4, 21.3,
22.8, 24.1, 29.0, 30.9, 41.2, 49.7, 62.0, 67.5, 73.0, 73.5, 74.7, 99.8,
101.7, 102.3, 126.9, 130.3, 133.6, 165.3, 199.2. Found: C, 61.96%,
H, 8.05%. Calcd for C22H34O8: C, 61.95%, H, 8.04%.
4.1.11. (100RS,20S,30E)-40-(400,400-Ethylenedioxy-1-hydroxy-
200,600,600-trimethyl-200-cyclohexen-100-yl)-30-buten-20-yl-[2,3-O-
(tetraisopropyldisiloxane-1,3-diyl)-4,6-O-isopropylidene]-b-
D-
glucopyranoside [(100RS,20S,30E)-16]
In the same manner just as described above, (20S)-isomer was
prepared from 1.48 g (2.08 mmol) of (100RS,20S)-isomer to give
1.10 g (74%) of (100RS,20S,30E)-16 as a colorless amorphous solid.
23
[
a]
D
–11.1 (c = 0.32, CHCl3). IR (film): t
max = 3503 cmꢀ1 (br.m,
OH), 2947–2869 (s), 1670 (w), 1092 (s), 834 (s). 1H NMR (CDCl3,
400 MHz): d = 0.86–1.20 (m, 34H), 1.23, 1.25 (d, J = 3.9 Hz, 3H),
1.35 (s, 3H), 1.43 (s, 3H), 1.63, 1.67 (d, J = 1.0 Hz, 3H), 1.72
(br.d, J = 14.2 Hz, 1H), 1.86, 1.88 (d, J = 14.2 Hz, 1H), 3.11 (ddd,
J = 4.9, 10.3, 10.7 Hz, 1H), 3.48–3.52 (m, 2H), 3.58 (m, 1H), 3.75
(ddd, J = 3.0, 10.3, 10.7 Hz, 1H), 3.86–3.98 (m, 5H), 4.32–4.37
(m, 1H), 4.34 (d, J = 7.3 Hz, 1H), 5.36, 5.38 (br.s, 1H), 5.57–5.64
(m, 2H). 13C NMR (CDCl3, 100 MHz): d = 11.9, 12.2, 12.8 (ꢁ2),
16.9, 17.1, 17.2, 17.3,18.0, 19.0, 22.1 (ꢁ2), 22.8, 23.1, 24.1, 24.8,
25.1, 29.0, 38.5, 38.6, 44.8 (ꢁ2), 62.3, 63.7, 63.9, 64.5, 66.8,
66.9, 67.0, 73.1, 74.4, 77.1, 77.4, 78.2, 78.4, 99.2 (ꢁ2), 100.2,
100.7, 104.8, 123.7, 123.8, 127.1, 131.6, 131.8, 133.1, 133.7,
133.8, 141.5, 141.7. Found: C, 60.62%, H, 9.04%. Calcd for
C36H64O10Si2: C, 60.63%, H, 9.05%.
4.1.13. (6R,9S)- and (6S,9S)-9-(40,60-O-Isopropylidene-b-
glucopyranosyl)oxy-6-hydroxy-3-oxo- -ionol (17)
D-
a
In the same manner as described above, (100RS,20S,30E)-16
(942 mg, 1.32 mmol) was converted to a diastereomeric mixture
of 17 (528 mg, 94%). The ratio of the isomers was estimated to
be 55:45 by 1H NMR analysis. MPLC separation of the diastereo-
mers (rate: 4 ml/min., toluene/THF = 10:1 to 3:1) gave pure
(6R,9S)-17 (72 mg) and (6S,9S)-17 (72 mg) as well as the diastereo-
meric mixture (380 mg).
22
Properties of (6 S,9S)-isomer: Colorless amorphous solid, [
+54.1 (c = 1.00, CHCl3). IR (film):
a]
D
t
max = 3447 cmꢀ1 (br.w, OH),
2972 (s), 1654 (s), 841 (s), 998 (s). 1H NMR (CDCl3, 400 MHz):
d = 0.99 (s, 3H), 1.07 (s, 3H), 1.32 (d, J = 6.4 Hz, 3H), 1.42 (s, 3H),
1.49 (s, 3H), 1.91 (s, 3H), 2.26 (br.d, J = 17.1 Hz, 1H), 2.49 (br.d,
J = 17.1 Hz, 1H), 3.18 (m, 1H), 3.45 (br.dd, J = 7.8, 8.3 Hz, 1H), 3.56
(m, 2H), 3.78 (dd, J = 10.3, 10.7 Hz, 1H), 3.89 (dd, J = 5.4, 10.7 Hz,
1H), 4.32 (d, J = 7.8 Hz, 1H), 4.41 (sep, J = 6.4 Hz, 1H), 5.75 (dd,
J = 6.4, 15.6 Hz, 1H), 5.87 (d, J = 15.6 Hz, 1H), 5.91 (s, 1H). 13C NMR
(CDCl3, 100 MHz): d = 19.0, 21.1, 22.0, 23.0, 24.2, 29.0, 30.9, 41.1,
49.6, 62.0, 74.5, 75.5, 77.2, 77.6, 79.8, 100.4, 127.0, 131.3,
132.1,167.1, 201.3. Found: C, 61.96%, H, 8.04%. Calcd for C22H34O8:
4.1.12. (6R,9R)- and (6S,9R)-9-(40,60-O-Isopropylidene-b-
glucopyranosyl)oxy-6-hydroxy-3-oxo- -ionol (17)
D-
a
To a stirred solution of (1”RS,20R,30E)-16 (1.89 g, 2.65 mmol) in
THF (28 ml) was added a mixture of 1 M TBAF in THF (11.1 ml,
11.1 mmol), THF (8 ml) and water (1 ml) at 0 °C. After stirring for
12 h, the mixture was poured into sat. NaHCO3 aq. and the aqueous
phase was extracted with EtOAc. The combined organic phases
wrer washed with brine and dried with Na2SO4. After concentra-
tion in vacuo, the residue was chromatographed on silica gel
(100 g, hexane/EtOAc = 1:5) to give crude material. The obtained
crude material was dissolved in ether (100 ml) and water (1 ml)
and acetic acid (20 ml) was successively added at room tempera-
ture. After stirring for 24 h, the reaction mixture was poured into
sat. NaHCO3 aq. and the aqueous phase was extracted with EtOAc.
The combined organic phases were washed with brine and dried
with Na2SO4. After concentration in vacuo, the residue was chro-
matographed on silica gel (90 g, hexane/EtOAc = 1:5) to give a dia-
stereomeric mixture of 17 (1.13 g, quant.). The ratio of the isomers
was estimated to be 55:45 by 1H NMR analysis. Preparative HPLC
separation (rate: 8.0 ml/min, hexane/EtOH = 8:1, Rt[(6S,9R)-
17] = 108.0 min, Rt[(6R,9R)-17] 124.7 min) gave pure (6S,9R)-17
(201 mg) and (6R,9R)-17 (264 mg) as well as the diastereomeric
mixture (660 mg).
C, 61.95%, H, 8.04%.
22
Properties of (6R,9S)-isomer: Colorless amorphous solid, [
a
]
D
–
134.9 (c = 1.00, CHCl3). 1H NMR (CDCl3, 400 MHz): d = 1.03 (s, 3H),
1.09 (s, 3H), 1.32 (d, J = 6.3 Hz, 3H), 1.43 (s, 3H), 1.50 (s, 3H), 1.89 (d,
J = 1.5 Hz, 3H), 2.27 (br.d, J = 17.1 Hz, 1H), 2.43 (br.d, J = 17.1 Hz,
1H), 3.21 (m, 1H), 3.47 (t, J = 7.8 Hz, 1H), 3.59 (m, 2H), 3.80 (dd,
J = 10.3, 10.7 Hz, 1H), 3.91 (dd, J = 5.4, 10.7 Hz, 1H), 4.35 (d,
J = 7.8 Hz, 1H), 4.41 (sep, J = 6.3 Hz, 1H), 5.71 (dd, J = 6.3, 16.1 Hz,
1H), 5.85 (d, J = 16.1 Hz, 1H), 5.91 (br.s, 1H). 13C NMR (CDCl3,
100 MHz): d = 18.8, 19.0, 22.0, 22.9, 24.3, 29.0, 41.0, 49.6, 62.0, 67.4,
73.0, 73.7, 74.5, 77.2, 99.8, 100.2, 127.2, 132.3, 132.6, 167.3, 201.2.
Found: C, 61.96%, H, 8.05%. Calcd for C22H34O8: C, 61.95%, H, 8.04%.
4.1.14. (6S,9S)-Roseoside (=corchoionoside C) (3)
To a solution of (6S,9S)-17 (72 mg, 169
lmol) in EtOH (1 ml)
and water (0.5 ml) was added a catalytic amount (ca. 2 mg) of

194
A. Yajima et al. / Bioorg. Med. Chem. 17 (2009) 189–194
pyridinium p-toluenesulfonate at room temperature. The reaction
mixture was stirred for 16 h at room temperature and at 50 °C
for 6 h. After cooling to room temperature, Et3 N was added to
the mixture. The solvent was removed by evaporation, and the res-
J = 6.3 Hz, 3H, 10-CH3), 1.85 (d, J = 1.5 Hz, 3H, 13-CH3), 2.08 (d,
J = 17.1 Hz, 1H, 2-CHH), 2.45 (d, J = 17.1 Hz, 1H, 2-CHH), 3.22 (m,
4H, 20,30,40,50-CH), 3.58 (dd, J = 5.4, 11.7 Hz, 1H, 60-CHH), 3.74 (dd,
J = 2.4, 11.7 Hz, 1H, 60-CHH), 4.29 (d, J = 7.8 Hz, 1H, 10-CH), 4.37
(m, 1H, 9-CH), 5.78 (m, 2H, 7,8-CH), 5.80 (br.s, 1H, 4-CH). 13C
NMR (CD3OD, 100 MHz): d = 19.7 (C-13), 21.2 (C-10), 23.4 (C-11),
24.6 (C-12), 42.4 (C-1), 50.7 (C-2), 62.5 (C-60), 71.3 (C-40), 75.1
(C-20), 76.9 (C-9), 77.8 (C-50), 77.9 (C-30), 79.9 (C-6), 102.5 (C-10),
127.0 (C-4), 131.6 (C-7), 135.0 (C-8), 167.3 (C-5), 201.2 (C-3).
Found: C, 59.05%, H, 7.83%. Calcd for C19H30O8: C, 59.05%, H, 7.83%.
idue was chromatographed on silica gel (27 g, CHCl3/MeOH = 10:1)
22
to give 65 mg (quant.) of 3 as a colorless amorphous solid. [a]
D
20
+60.4 (c = 0.96, MeOH), lit.2l
[
a
]
+31.2 (c = 2.0, MeOH), lit.3
D
25
[a
]
D
+74.0 (c = 0.96, MeOH). IR (film): t
max = 3430 cmꢀ1 (br.s,
OH), 2970–2928 (m), 1654 (s), 1073 (s), 1036 (s). 1H NMR (CD3OD,
400 MHz): d = 0.95 (s, 3H, 11-CH3), 0.97 (s, 3H, 12-CH3), 1.22 (d,
J = 6.3 Hz, 3H, 10-CH3), 1.87 (d, J = 1.5 Hz, 3H, 13-CH3), 2.10 (d,
J = 17.1 Hz, 1H, 2-CHH), 2.54 (d, J = 17.1 Hz, 1H, 2-CHH), 3.06–
3.38 (m, 4H, 20,30,40,50-CH), 3.56 (dd, J = 6.3, 11.7 Hz, 1H, 60-CHH),
3.78 (dd, J = 2.0, 11.7 Hz, 1H, 60-CHH), 4.20 (d, J = 7.8 Hz, 1H, 10-
CH), 4.46 (m, 1H, 9-CH), 5.63 (dd, J = 7.3, 15.6 Hz, 1H, 8-CH), 5.80
(s, 1H, 4-CH), 5.91 (d, J = 15.6 Hz, 1H, 7-CH). 13C NMR (CD3OD,
100 MHz): d = 19.6 (C-13), 22.2 (C-10), 23.5 (C-11), 24.7 (C-12),
42.4 (C-1), 50.8 (C-2), 62.8 (C-60), 71.7 (C-40), 74.6 (C-9), 74.9 (C-
20), 78.2 (C-50), 78.4 (C-30), 80.0 (C-6), 101.2 (C-10), 127.1 (C-4),
133.7 (C-8), 133.8 (C-7), 167.1 (C-5), 201.3 (C-3). Found: C,
59.06%, H, 7.83%. Calcd for C19H30O8: C, 59.05%, H, 7.83%.
5. Cell culture and stimulation8
Femoral bone marrow cells derived from male ICR (Nippon
SLC) mice were cultured in IL-3-containing medium (10 ng/ml)
for more than 8 weeks to generate >95% pure populations of
bone marrow-derived cultured mast cell (BMCMC). BMCMC were
incubated with 1 mg/ml of anti-DNP mouse IgE (SPE-7, Sigma Al-
drich) for 6 h with or without 100 mM of roseoside. For FceRI
cross-linking, cells were further incubated with antigen, 10 ng/
ml of DNP-HSA for 30 min.
4.1.15. (6S,9R)-Roseoside (4)
6. Measurements of leukotrienes
In the same manner as described above, (6S,9R)-17 (201 mg,
169
(c = 1.02, MeOH), lit.2a
+109.4 (c = 0.96, MeOH). IR (film):
lmol) was converted to 4 (180 mg, 99%). [
a
]
22 = +116.2
D
Amounts of leukotoriens in BMCMC culture supernatants were
measured by using commercial kit (Buhlman CAST ELISA kit).
19
[
a]
+112 (c = 1.19, MeOH), lit.3
[a]
D
D
t
max = 3409 cmꢀ1 (br.s, OH),
2972–2931 (m), 1655 (s), 1075 (s), 1036 (s). 1H NMR (CD3OD,
400 MHz): d = 0.98 (s, 6H, 11,12-CH3), 1.23 (d, J = 6.4 Hz, 3H, 10-
CH3), 1.87 (d, J = 1.5 Hz, 3H, 13-CH3), 2.10 (d, J = 17.1 Hz, 1H, 2-
CHH), 2.47 (d, J = 17.1 Hz, 1H, 2-CHH), 3.10–3.32 (m, 4H,
20,30,40,50-CH), 3.58 (dd, J = 5.4, 11.7 Hz, 1H, 60-CHH), 3.80 (dd,
J = 2.0, 11.7 Hz, 1H, 60-CHH), 4.29 (d, J = 7.3 Hz, 1H, 10-CH), 4.37
(m, 1H, 9-CH), 5.80–5.82 (m, 3H, 4,7,8-CH). 13C NMR (CD3OD,
100 MHz): d = 19.5 (C-13), 21.2 (C-10), 23.4 (C-11), 24.7 (C-12),
42.4 (C-1), 50.6 (C-2), 62.8 (C-60), 71.6 (C-40), 75.2 (C-20), 77.3 (C-
9), 77.9 (C-50), 78.0 (C-30), 80.0 (C-6), 102.7 (C-10), 127.1 (C-4),
131.5 (C-7), 135.2 (C-8), 167.2 (C-5), 201.2 (C-3). Found: C,
59.06%, H, 7.82%. Calcd for C19H30O8: C, 59.05%, H, 7.83%.
Acknowledgments
We thank Mr. D. Kanda for his experimental help. This work
was supported by a grant from Advanced Research Project of Tokyo
University of Agriculture.
References and notes
1. Yoshikawa, M.; Shimada, H.; Saka, M.; Yoshizumi, S.; Yamahara, J.; Matsuda, H.
Chem. Pharm. Bull. 1997, 45, 464–469.
2. (6S,9R)-isomer: (a) Bhakuni, D. S.; Joshi, P. P.; Uprety, H.; Kapil, R. S.
Phytochemistry 1974, 13, 2541–2543; (b) Sasaki, H.; Taguchi, H.; Endo, T.;
Yosioka, I.; Higashiyama, K.; Otomasu, H. Chem. Pharm. Bull. 1978, 26, 2111–
2121; (c) Achenbach, H.; Waibel, R.; Raffelsberger, B.; Addae-Mensah, I.
Phytochemistry 1981, 20, 1591–1595; (d) Okamura, N.; Yagi, A.; Nishioka, I.
Chem. Pharm. Bull. 1981, 29, 3507–3514; (e) Andersson, R.; Lundgren, L. N.
Phytochemistry 1988, 27, 559–562; (f) Otsuka, H.; Takeda, Y.; Yamasaki, K.;
Takeda, Y. Planta Med. 1992, 58, 373–375; (g) Cui, B.; Nakamura, M.; Kinjo, J.;
Nohara, T. Chem. Pharm. Bull. 1993, 41, 178–182; (6R,9R)-isomer: (h) Otsuka, H.;
Yao, M.; Kamada, K.; Takeda, Y. Chem. Pharm. Bull. 1995, 43, 754–759; (6S,9S)-
isomer: (i) Du, X.; Sun, N.; Irino, N.; Shoyama, Y. Chem. Pharm. Bull. 2000, 48,
1803–1804; (j) Murai, Y.; Kashimura, S.; Tamezawa, S.; Hashimoto, T.; Takaoka,
S.; Asakawa, Y.; Kiguchi, K.; Murai, F.; Tagawa, M. Planta Med. 2001, 67, 480–
481; (k) Yu, Q.; Otsuka, H.; Hirata, E.; Shinzato, T.; Takeda, Y. Chem. Pharm. Bull.
2002, 50, 640–644; (l) Çalis, Í.; Kuruüzüm-Uz, A.; Lorenzetto, P. A.; Rüedi, P.
Phytochemistry 2002, 59, 451–457; (m) Kanchanapoom, T.; Chumsri, P.; Kasai,
R.; Otsuka, H.; Yamasaki, K. Phytochemistry 2003, 63, 985–988; (n) Lee, E.; Kim,
H.; Song, Y.; Jin, C.; Lee, K.; Cho, J.; Lee, Y. Arch. Pharm. Res. 2003, 26, 1018–1023;
(o) Nakanishi, T.; Iiida, N.; Inatomi, Y.; Murata, H.; Inada, A.; Murata, J.; Lang, F.
A.; Iinuma, M.; Tanaka, T.; Sakagami, Y. Chem. Pharm. Bull. 2005, 53, 783–787;
(p) Cutillo, F.; Dellagreca, M.; Previtera, L.; Zarrelli, A. Nat. Prod. Res. 2005, 19,
99–103; (q) Sawabe, A.; Nesumi, C.; Morita, M.; Matsumoto, S.; Matsubara, Y.;
Komemushi, S. J. Oleo Sci. 2005, 54, 185–191; Stereochemistry unknown: (r)
Tschesche, R.; Ciper, F.; Harz, A. Phytochemistry 1976, 15, 1990–1991; (s)
Kodama, H.; Fujimori, T.; Kato, K. Agric. Biol. Chem. 1981, 45, 941–944; (t)
Baltenweck-Guyot, R.; Trendel, J.; Albrecht, P.; Schaeffer, A. Phytochemistry 1996,
43, 621–624; (u) Ito, K.; Tanabe, Y.; Kato, S.; Yamamoto, T.; Saito, A.; Mori, M.
Biosci. Biotechnol. Biochem. 2000, 64, 584–587.
4.1.16. (6R,9S)-Roseoside (5)
In the same manner as described above, (6R,9S)-17 (72 mg,
22
170
(c = 0.80, MeOH), lit.3
max = 3410 cmꢀ1 (br.s, OH), 2971–2929 (m), 1653 (s), 1071 (s),
l
mol) was converted to 5 (66 mg, quant.). [
a
]
–137.4
D
26
[
a]
D
–157.5 (c = 0.80, MeOH). IR (film):
t
1035 (s). 1H NMR (CD3OD, 400 MHz): d = 0.97 (s, 6H, 11,12-CH3),
1.20 (d, J = 6.3 Hz, 3H, 10-CH3), 1.84 (d, J = 1.6 Hz, 3H, 13-CH3),
2.10 (d, J = 17.1 Hz, 1H, 2-CHH), 2.47 (d, J = 17.1 Hz, 1H, 2-CHH),
3.10–3.28 (m, 4H, 20,30,40,50-CH), 3.56 (dd, J = 5.9, 12.2 Hz, 1H, 60-
CHH), 3.80 (dd, J = 2.0, 12.2 Hz, 1H, 60-CHH), 4.24 (d, J = 7.8 Hz,
1H, 10-CH), 4.46 (m, 1H, 9-CH), 5.63 (dd, J = 7.8, 15.6 Hz, 1H, 8-
CH), 5.79 (s, 1H, 4-CH), 5.89 (d, J = 15.6 Hz, 1H, 7-CH). 13C NMR
(CD3OD, 100 MHz): d = 19.4 (C-13), 22.2 (C-10), 23.4 (C-11), 24.8
(C-12), 42.3 (C-1), 50.6 (C-2), 62.9 (C-60), 71.7 (C-40), 74.7 (C-9),
75.0 (C-20), 78.1 (C-50), 78.2 (C-30), 80.0 (C-6), 100.9 (C-10), 127.2
(C-4), 133.8 (C-8), 134.1 (C-7), 166.9 (C-5), 201.1 (C-3). Found: C,
59.05%, H, 7.83%. Calcd for C19H30O8: C, 59.05%, H, 7.83%.
3. Yamano, Y.; Ito, M. Chem. Pharm. Bull. 2005, 53, 541–546.
4. Paulsen, H.; Kolár, C. Chem. Ber. 1981, 114, 306–321.
4.1.17. (6R,9R)-Roseoside (6)
In the same manner as described above, (6 R,9R)-17 (264 mg,
5. Marco-Contelles, J.; Ariente, C. Carbohydrate Lett. 1997, 2, 245–252.
6. Mori, K.; Tominaga, M.; Takigawa, T.; Matsui, M. Synthesis 1973, 790–791.
7. Mayer, H.; Montavon, M.; Ruegg, R.; Isler, O. Helv. Chim. Acta 1967, 50, 1606–
1618.
8. Kitaura, J.; Song, J.; Tsai, M.; Asai, K.; Maeda-Yamamoto, M.; Mocsai, A.;
Kawakami, Y.; Liu, F.-T.; Lowel, C. A.; Barisas, B. G.; Galli, S. J.; Kawakami, T. Proc.
Natl. Acad. Sci. U. S. A. 2003, 100, 12911–12916.
22
619
l
mol) was converted to 6 (230 mg, 96%). [
a]
D
–101.3
22
19
(c = 0.79, MeOH), lit.2h
[
a]
D
–74.0 (c = 0.23, MeOH), lit.3
[
a]
D
–
116.0 (c = 0.79, MeOH). IR (film):
t
max = 3400 cmꢀ1 (br.s, OH),
2972–2931 (m), 1653 (s), 1076 (s), 1035 (s). 1H NMR (CD3OD,
400 MHz): d = 0.93 (s, 3H, 11-CH3), 0.96 (s, 3H, 12-CH3), 1.23 (d,