Synthesis of the glycosidic precursor of isomeric marmelo lactones, volatile components of the quince fruit, Cydonia oblonga.

Article abstract of DOI:10.1271/bbb.66.743

The glucosidic precursor of marmelo lactones was synthesized by employing a common intermediate which had been used for the synthesis of the glucosidic precursor of marmelo oxides. The synthesis was performed by modifying the former procedure. Monochloroa

Full text of DOI:10.1271/bbb.66.743

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Synthesis of the Glycosidic Precursor of Isomeric
Marmelo Lactones, Volatile Components of the
Quince Fruit, Cydonia oblonga
Hiroki SHIMIZUa & Takeshi KITAHARAa
a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life
Sciences, The University of Tokyo1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Published online: 22 May 2014.
To cite this article: Hiroki SHIMIZU & Takeshi KITAHARA (2002) Synthesis of the Glycosidic Precursor of Isomeric Marmelo
Lactones, Volatile Components of the Quince Fruit, Cydonia oblonga , Bioscience, Biotechnology, and Biochemistry, 66:4,
743-748, DOI: 10.1271/bbb.66.743
To link to this article: http://dx.doi.org/10.1271/bbb.66.743
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Biosci. Biotechnol. Biochem., 66 (4), 743–748, 2002
Synthesis of the Glycosidic Precursor of Isomeric Marmelo Lactones,
Volatile Components of the Quince Fruit, Cydonia oblonga
†
Hiroki SHIMIZU and Takeshi KITAHARA
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences,
The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Received September 10, 2001; Accepted November 12, 2001
The glucosidic precursor of marmelo lactones was
synthesized by employing a common intermediate which
had been used for the synthesis of the glucosidic precur-
sor of marmelo oxides. The synthesis was performed by
modifying the former procedure. Monochloroacetyl
was adopted to protect both the glucose and aglycon
hydroxyl groups for selective transesteriˆcation in the
presence of the glycosyl ester. Glycosylation of the agly-
of ester glycoside 1 by using a similar strategy.
Results and Discussion
As shown in Scheme 1, the acetyl-protected agly-
con 6 of 1 was prepared from alcohol 5 which had
been used for the synthesis of 2.8) A two-step se-
quence involving Dess-martin oxidation and succes-
sive chlorite oxidation enabled alcohol 5 to be con-
verted to carboxylic acid 6. The glycosylation reac-
tion was initially performed with glucosyl trichloroa-
cetimidate 7 and TMSOTf in the same manner as that
con carboxyl group with 1-a-bromopermonochloroa-
cetylglucose and ˆnal selective alcoholysis yielded the
target glucoside.
for the synthesis of 29) to give glucoside 8 in a 33
z
Key words: quince fruit; Cydonia oblonga Mill.;
glycosidic precursor; volatile component;
selective alcoholysis
yield. However, during deprotection of the acetate
groups with methanolic sodium methoxide, the
glycosyl ester was simultaneously methanolyzed.
In order to overcome this di‹culty, we adopted the
monochloroacetyl group instead of the acetyl group
for protecting both the glucose and aglycon hydroxyl
groups, since monochloroacetate is known to be
more labile than acetate during hydrolysis10)
(Scheme 2). Known intermediate 10 for the synthesis
of 28) was converted to monochloroacetyl ester 11.
Under strongly acidic or basic conditions such as HF-
Progress in analytical technology has enabled more
than 200 kinds of natural glycosidic bound compo-
nents to be found, including terpenoids and nonter-
penoids, and their structures, biosyntheses and roles
in the plant kingdom have been elucidated since the
1980s.1–4)
Monoterpene glycosides 1 and 2 are precursors of
the main volatile components, marmelo lactones 3
and marmelo oxides 4, in quince fruit, Cydonia Ob-
longa Mill., which are important for the characteris-
tic odor of this fruit (Fig. 1). In 1991, Schreier and
co-workers isolated and characterized the structures
of 15) and 2,6) and at almost the same time, Na
ä f and
Velluz reported several non-glycosidic bound acyclic
precursors, including that of 1 and 2,7) from an en-
zymatic hydrolysate of the glycosidic fraction ex-
tracted from quince fruit.
Synthetic studies to enable a stable supply of the
glycosidic precursors of volatile compounds would
be very useful for further research in this area such as
revealing the mechanism for generating the volatile
components, clarifying the metabolisms and signals
in the plant and preparing for future industrial uses.
We thus embarked upon the syntheses of compounds
1 and 2, at the synthesis of 2 already having been
achieved and reported.8) We now report the synthesis
Fig. 1.
†
To whom correspondence should be addressed. Tel: 81-3-5841-5119; Fax: 81-3-5841-8019; E-mail: atkita
＠
mail.ecc.u-tokyo.ac.jp

744
H. SHIMIZU and T. KITAHARA
Scheme 1.
Scheme 2.
pyridine or TBAF, the diene moiety was isomerized
to give an ( ) mixture during desilylation.
Consequently, deprotection was carried out with
THF–AcOH–H2O to give pure (
)-12,11) whose
eŠect of the solvent on the stereochemistry of the
product was remarkable and, in the case of methy-
E, Z
lene chloride, the ratio of glucoside isomers was
3:2. In the case of acetonitrile (r.t. for 2d),15) only
-glucoside 16 (41 ) was produced. The last step,
a: b
E
,
E
＝
hydroxyl group was oxidized with the Dess-Martin
reagent and then with sodium chlorite to give carbox-
ylic acid 13. The gylcosylation reaction was also at-
tempted with 13 and permonochloroacetylated
glucosyl trichloroacetimidate 15,12) but the adduct
decomposed and the desired glycosyl ester could not
be obtained. The Mitsunobu reaction was then at-
tempted to couple 13 and 15,13) but only a trace
b
z
deprotection of the monochloroacetyl group, was
attempted under various conditions. During the
transesteriˆcation of 16 with MeOH and ion-
exchange resin16) of the strongly basic type (Dowex 1
×
8 20–50 mesh), the aglycon methyl ester emerged
before the glucoside had been completely deprotect-
ed. Neither the monochloroacetyl nor glycosyl ester
was cleaved with resin of the weakly base type (Am-
berlite IR-45 or IR-4B). When hydrazine dithiocar-
bonate was used,17) deprotection seemed to be suc-
cessful by TLC observation, although puriˆcation
was much too di‹cult since both the product and
amount of the a b mixture of glucoside 16 was
W
aŠorded.
We ˆnally examined the coupling of tetra-
monochloroacetylglucosyl bromide 1714) with agly-
con 13 in the presence of Ag2CO3 (Scheme 3). The

Synthesis of the Glycosidic Precursor of Marmelo Lactones
745
Scheme 3.
reagents were extremely polar. When thiourea
cooling. After stirring for 15 minutes at r.t., the reac-
tion mixture was poured into cooled sat. NaHCO3
aq. and extracted with EtOAc. The organic layer was
washed with sat. NaCl aq., dried with MgSO4, and
concentrated in vacuo. The residue was puriˆed by
derivative 18 was employed,18) transesteriˆcation was
achieved to give 1 in a 79
16
z yield. The total yield was
z
in 6 steps from 10. The structure of synthetic
glycoside 1 was identiˆed by its transformation to the
1
peracetyl derivative. H-NMR data for the product
silica gel column chromatography (n-Hexane:EtOAc
were indistinguishable from those of 8.5)
＝
35:1) to give 0.190 g (quant.) of 11 as a colorless
In conclusion, we synthesized ester-type glycosidic
precursor 1 that had been isolated from quince fruit
by employing common intermediate 10 which had
also been used for our synthesis of glycoside 2. In this
particular case, the key step was selective removal of
the ester protecting groups in the glucosyl moiety by
using the more labile monochloroacetyl groups. The
oil. [
a
]
23 +1.6
9
(
c
0.12, CHCl3). IR
n
max (ˆlm) cm„1
:
D
2955 (S), 1761 (S), 1471 (m), 1255 (m), 1164 (m),
1
1094 (m), 966 (m), 837 (S), 776 (m), 667 (w). H-
NMR
0.86 (3H, d,
1.69 (1H, m, H-7), 1.78 (3H, brs, CH3-2), 1.95 (1H,
ddd, 7.3 and 14.6, H-6a), 2.24 (1H, ddd, 7.3
and 13.8, H-6b), 3.41 (2H, d, 6.0, H-8), 4.08 (2H,
s, ClCH2C(O)), 4.62 (2H, s, H-1), 5.75 (1H, dt,
7.1 and 14.3, H-5), 6.17 (1H, d, 11.3, H-3),
11.3 and 14.3, H-4). Anal. Calcd.
for C18H33ClO3Si: C, 59.89; H, 9.21 . Found: C,
59.79; H, 9.03
d (CDCl3, 300 MHz): 0.03 (6H, s, CH3–Si),
J
＝
6.8, CH3-7), 0.89 (9H, s, t-Bu–Si),
J
＝
J
＝
＝
J
synthesis was achieved in a 5.1
steps from methyl (
ate.
z
overall yield by 13
S)-3-hydroxy-2-methylpropano-
J
＝
J
＝
＝
J
6.22 (1H, dd,
z
Experimental
z
.
General experimental procedure. NMR spectra
were recorded at 90 MHz by a Jeol JMN-EX90
instrument in CDCl3 and at 300 MHz by a Bruker
(R,2E,4E)-2,7-Dimethyl-8-hydroxy-2,4-octadien-
1-yl chloroacetate (12). Chloroacetate 11 was dis-
solved in AcOH–H2O–THF (13:3:7, 40 ml) and
stirred for 4.5 h at r.t. The reaction mixture was
poured into sat. NaHCO3 aq. and extracted with
EtOAc. The organic layer was washed with sat. NaCl
AC-300 instrument in CDCl3 or MeOH-d4. IR spec-
tra were measured as ˆlms by a Jasco A-102 spec-
trometer, and HRMS measurements were performed
with Jeol JMS-SX102 SX102 and Jeol JMS700
W
instruments. Optical rotation values were measured
by a Jasco DIP 371 polarimeter. Merck Kieselgel 60
(Art. no. 7734) and Kanto Chemical silica gel 60 N
were used for column chromatography.
aq., dried with MgSO4 and concentrated in vacuo
.
The residue was puriˆed by silica gel chro-
＝
(n-Hexane:EtOAc 14:1) to give
matography
0.720 g (quant.) of 12 as a colorless oil. [
0.12, CHCl3). IR
a
]
22 +13.0
9
D
(c
n
max (ˆlm) cm„1: 3361 (br.s, OH),
(R,2E,4E)-8-t-Butyldimethylsilyloxy-2,7-dimethyl-
2,4-octadien-1-yl chloroacetate (11). To a solution of
10 (0.15 g, 0.522 mmol) in CH2Cl2 (3 ml) were added
monochloroacetic anhydride (0.464 g, 2.71 mmol)
and triethylamine (0.253 ml, 1.08 mmol) while ice-
2925 (S), 1755 (S), 1454 (m), 1308 (m), 1170 (S), 1035
(m), 967 (m), 759 (w). 1H-NMR
(CDCl3, 300 MHz):
6.7, CH3-7), 1.75 (1H, m, H-7), 1.78
d
＝
J
0.92 (3H, d,
(3H, s, CH3-2), 2.02 (1H, ddd,
6a), 2.24 (1H, ddd, 6.9 and 13.4), 3.48 (2H, ddd,
＝
J
6.6 and 13.7, H-
J
＝

746
H. SHIMIZU and T. KITAHARA
＝
J
5.9 and 6.2, H-8), 4.08 (2H, s, ClCH2C(O)), 4.61
The residue was puriˆed by neutral silica gel
＝
＝
chromatography (n-Hexane:EtOAc 15:1) to give
(2H, s, H-1), 5.75 (1H, dt,
6.07 (1H, d,
and 15.0, H-4). Anal. Calcd. for C12 H19ClO3: C,
58.42; H, 7.76 . Found: C, 58.51; H, 7.68
J
7.4 and 15.0, H-5),
＝
＝
10.7
J
10.7, H-3), 6.25 (1H, dd,
J
z
0.075 g (76 ) of an aldehyde as a colorless oil. IR
nmax (ˆlm) cm„1: 3035 (m), 2973 (m), 2933 (m), 2717
z
z
.
(m), 1731 (S), 1455 (m), 1374 (m), 1229 (s), 1022 (m),
1
969 (m), 877 (m). H-NMR
d (CDCl3, 300 MHz):
＝
6.8, CH3-7), 1.77 (3H, s, CH3-2),
(R,4E,6E)-8-Chloroacetoxy-2,7-dimethyl-4,6-
octadienoic acid (13). To a solution of 12 (0.74 g,
2.88 mmol) in CH2Cl2 (30 ml) was added Dess-Mar-
tin periodinane (1.34 g, 3.17 mmol) while ice-cooling
in an N2 atmosphere. After stirring for 30 min, the
1.11 (3H, d,
2.08 (3H, s, CH3C(O)), 2.23 (1H, ddd,
14.6, H-6a), 2.45 (1H, m, H-7), 2.54 (1H, ddd,
7.3 and 13.8, H-6b), 4.50 (2H, s, H-1), 5.67 (1H, dt,
J
＝
J
7.3 and
＝
J
＝
＝
J
7.1 and 14.0, H-5), 6.03 (1H, d,
J
10.1, H-3),
＝
6.29 (1H, dd, J
＝
reaction mixture was poured into 5
z
Na2S2O3 aq.
10.1 and 14.0, H 4), 9.65 (1H, s,
＝
To
and extracted with CH2Cl2. The organic layer was
successively washed with sat. NaHCO3 aq. and sat.
NaCl aq., dried with MgSO4 and concentrated in
vacuo. The residue was puriˆed by silica gel chro-
H
8).
a
solution of this aldehyde (0.075 g,
0.357 mmol) obtained from 5, 2-methyl-2-butene
(0.33 ml, 3.21 mmol) and KH2PO4 (0.048 g,
＝
matography (
(66 ) of an aldehyde as a colorless oil. [
0.32, CHCl3). IR
max (ˆlm) cm„1: 2932 (S), 2720 (m),
1730 (S), 1455 (m), 1413 (m), 1373 (m), 1309 (m),
n
-Hexane:EtOAc 12:1) to give 0.43 g
3.57 mmol) in H2O–
t-BuOH (1:5, 30 ml) was added
z
a
]2D2 „3.3
9
(
c
85 NaClO2 (0.131 g, 12.5 mmol) while ice-cooling.
z
n
After stirring for 12 h, the reaction mixture was aci-
diˆed to pH 3 with 1 N HCl aq. and extracted with
CHCl3. The organic layer was dried with MgSO4 and
concentrated in vacuo. The residue was puriˆed by
1169 (S), 969 (m), 760 (w). 1H-NMR
d
(CDCl3,
＝
J
300 MHz): 1.11 (3H, d,
CH3-2), 2.23 (1H, ddd,
J
6.9, CH3-7), 1.78 (3H, s,
＝
＝
silica gel chromatography (n-Hexane:EtOAc 10:1
7.4 and 14.8, H-6a),
2.39–2.58 (2H, m, H-6b and H-7), 4.08 (2H, s,
+1z AcOH) to give 0.0578 g (71z) of 6 as a slightly
ClCH2C(O)), 4.62 (2H, s, H-1), 5.57 (1H, dt,
J
＝
7.4
10.2, H-3), 6.26 (1H,
10.2 and 14.8, H-4), 9.67 (1H, s, H-8). Anal.
Calcd. for C12H17ClO3: C, 58.90; H, 7.00 . Found:
C, 58.66; H, 6.93
yellow oil. IR nmax (ˆlm) cm„1: 3680–3100 (br.m),
＝
and 14.8, H-5), 6.06 (1H, d,
J
2780–2440 (br.m), 2977 (S), 1731 (S), 1456 (m), 1377
1
＝
dd,
J
(m), 1233 (s), 1023 (m), 970 (m). H-NMR
d
(CDCl3,
z
300 MHz): 1.25 (3H, d,
CH3-7), 2.13 (3H, s, CH3C(O)), 2.33 (1H, ddd,
7.3 and 14.6, H-3a), 2.54 (1H, ddd, 7.3 and 13.8,
H-3b), 2.61 (1H, m, H-2), 4.55 (2H, s, H-8), 5.73
J 6.8, CH3-2), 1.82 (3H, s,
＝
＝
J
z.
To a solution of the aldehyde (0.46 g, 1.88 mmol),
2-methyl-2-butene (2.0 ml, 18.8 mmol) and KH2PO4
(0.89 g, 6.58 mmol) in H2O–
added 85 NaClO2 (0.7 g, 6.58 mmol) with ice cool-
J
＝
＝
＝
10.9,
t
-BuOH (1:5, 15 ml) was
(1H, dt,
J
7.5 and 15.0, H-4), 6.08 (1H, d,
J
H-6), 6.35 (1H, dd, J
＝
10.9 and 15.0, H-5).
z
ing. After stirring for 30 min at r.t., the mixture was
acidiˆed to pH 3 with 1 N HCl aq. and extracted with
CHCl3. The organic layer was dried with MgSO4 and
concentrated in vacuo. The residue was puriˆed by
2
?
,3
(R,4E,6E)-8-acetoxy-2,7-dimethyl-4,6-octadienoate
). To the suspension of 6 (0.021 g, 0.0928 mmol)
?
,4
?
,6
?
-Tetra-O-acetyl-
b
- -glucopyranosyl
D
(8
silica gel chromatography (
n
-Hexane:EtOAc
＝
8:1
and MS AW 300 molecular sieves (ca. 0.01 g) in
CH2Cl2 (1.0 ml) were successively added 7 (0.117 g,
0.237 mmol) and TMSOTf (2.52 ml, 13.92 mmol) at
+1
z AcOH) to give 0.37 g (76z) of 13 as slightly
yellow oil. IR nmax (ˆlm) cm„1: 3700–3470 (br.m),
2979 (s), 2440–2780 (br.m), 1747 (s), 1712 (s), 1455
(m), 1415 (m), 1371 (m), 1308 (m), 1170 (s), 971 (m),
9
„78 C. After stirring for 100 min, sat. NaHCO3 aq.
was added, and the reaction mixture was allowed to
stand at ambient temperature. The mixture was ex-
tracted with CH2Cl2. The organic layer was washed
with sat. NaCl aq., dried with MgSO4 and concen-
trated in vacuo. The residue was puriˆed by neutral
790 (m). 1H-NMR
d (CDCl3, 300 MHz): 1.20 (3H, d,
6.8, CH3-2), 1.78 (3H, s, CH3-7), 2.31 (1H, ddd,
7.0 and 13.9, H-3a), 2.47–2.61 (2H, m, H-3b and
＝
＝
J
J
H-2), 4.09 (2H, s, H-8), 4.62 (2H, s, ClCH2C(O)),
5.71 (1H, dt,
11.0, H-6), 6.29 (1H, dd,
＝
＝
＝
n-Hexane:EtOAc 15:1)
1
J
7.3 and 14.6, H-4), 6.06 (1H, d,
J
silica gel chromatography (
to give 0.0169 g (32.7 ) of 8 as a colorless oil. H-
NMR (CDCl3, 300 MHz): 1.14 (3H, d,
CH3-2), 1.77 (3H, s, CH3-7), 2.02, 2.03, 2.04, 2.078,
J
＝
11.0 and 14.6, H-5).
z
＝
6.8,
d
J
(R,4E,6E)-8-Acetoxy-2,7-dimethyl-4,6-octadienoic
acid ( ). To a solution of 5 (0.1 g, 4.71 mmol) in
＝
6
2.084 (15H, 5s, CH3C(O)), 2.26 (1H, ddd,
J
7.3
7.3 and 13.8, H-
3b), 2.58 (1H, m, H-2), 3.85 (1H, m, H-5 ), 4.11
＝
and 14.6, H-3a), 2.46 (1H, ddd, J
CH2Cl2 (30 ml) was added Dess-Martin perindinane
(0.4 g, 0.943 mmol) while ice cooling. After stirring
?
＝
＝
?a), 4.31 (1H, dd, J
for 15 min, the reaction mixture was poured into 5
z
(1H, dd,
3.8 and 16.9, H-6
J
2.2 and 16.9, H-6
Na2S2O3 aq. and extracted with CHCl3. The organic
layer was successively washed with sat. NaHCO3 aq.
and sat. NaCl aq., dried with MgSO4 and concen-
?
b), 4.49 (2H, s, H-8), 5.05–5.31
＝
＝
(3H, m, H
15.8, H-5), 5.71 (1H, d,
9.0, H-3), 6.28 (1H, dd,
2
?
, 3
?
, 4
?
), 5.57 (1H, dt,
J
7.1 and
), 6.00 (1H, d,
9.0 and 15.8, H 4).
＝
J
8.3, H-1?
trated in vacuo
.
J
＝
J
＝
＝

Synthesis of the Glycosidic Precursor of Marmelo Lactones
747
2
?
,3
?
,4
?
,6
?
-Tetra-O-chloroacetyl-
b
-
D
-glucopyra-
was partly supported by grant-aid for scientiˆc
research from the Japanese Ministry of Science, Edu-
cation, Culture and Sport (No. 09460056).
nosyl (R,4E,6E)-8-chloroacetoxy-2,7-dimethyl-
4,6-octadienoate (16). To a suspension of 13 (0.085 g,
0.328 mmol) and 17 (0.18 g, 0.328 mmol) and MS
AW 300 molecular sieves (ca. 0.01 g) in CH3CN
(3.0 ml) was added Ag2CO3 (0.055 g, 0.197 mmol).
After stirring for 2d at r.t. in the dark, the reaction
mixture was ˆltered, and the ˆltrate poured into
water. The mixture was extracted with EtOAc. The
organic layer was dried with MgSO4 and concentrat-
References
1) Stahl-Biskup, E., Monoterepene glycosides, state-of-
the-art. Flavour Fragr. J., 2, 75–82 (1987).
2) Mulkens, A., Les he
á teá rosides monoterpeá niques non
iridoƒ
ä
des. Pharm. Acta Helv., 62, 229–235 (1987).
3) Stahl-Biskup, E., Intert, F., Holthuijzen, J., Sten-
gele, M., and Schulz, G., Glycosidically bound
volatiles—A review 1986–1991. Flavour Fragr. J., 8,
61–80 (1993).
4) Schreier, P. and Winterdelter, P., Eds., Progress in
Flavour Precursor Studies; Proceedings of the Inter-
ed in vacuo
.
The residue was puriˆed by neutral silica gel chro-
＝
matography (n-Hexane–EtOAc 7:1) and then treat-
ed with Biobead} to give 0.0978 g (41.0
z) of b-16 as
a colorless oil. IR nmax (ˆlm) cm„1: 3030 (m), 2957
(S), 1768 (s), 1496 (w), 1458 (m), 1411 (m), 1375 (m),
1310 (s), 1157 (S), 1076 (s), 1004 (m), 964 (m), 794
national Conference, Wu
ä rzburg, Allured Publishing
Corp. 1993.
(m), 759 (s), 697 (m). 1H-NMR
d
(CDCl3, 300 MHz):
6.9, CH3-2), 1.78 (3H, s, CH3-7),
7.5 and 15.0, H-3a), 2.47 (1H,
7.5 and 15.0, H-3b), 2.59 (1H, m, H-2), 3.76
(1H, t, H-5 ), 3.97, 4.01, 4.03, 4.09, 4.12 (10H, 5s,
ClCH2C(O)), 4.30 (1H, dd,
5) Lutz, A., Winterhalter, P., and Schreier, P., Isola-
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5943–5944 (1991).
＝
J
1.16 (3H, d,
2.26 (1H, ddd,
J
＝
＝
J
ddd,
6) Winterhalter, P., Lutz, A., and Schreier, P., Isola-
tion of a glucosidic precursor of isomeric marmelo
lactones from quince fruit. Tetrahedron Lett., 32,
3669–3670 (1991).
?
＝
J
3.8 and 15.0, H-6
4.1 and 15.0, H-6 b), 4.62 (2H, s,
H-8), 5.25 (2H, m, H-2 and H-3 ), 5.40 (1H, t,
9.5, H-4 ), 5.58 (1H, dt, 7.5 and 15.0, H-4), 5.78
?a),
＝
4.40 (1H, dd,
J
?
?
?
J
＝
7) Naä f, R. and Velluz, A., Isolation of acyclic precur-
＝
J
?
J
sors of the marmelo oxides, the marmelo lactones and
the quince oxepine from quince fruit (Cydonia oblon-
ga Mil.). Tetrahedron Lett., 32, 4487–4490 (1991).
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＝
＝
12.8, H-6),
(1H, d,
6.39 (1H, dd,
8.3, H-1
?
), 6.05 (1H, d,
J
J
＝
12.8 and 15.0, H-5).
b
-
D
-Glucopyranosyl (R,4E,6E)-8-hydroxy-2,7-
dimethyl-4,6-octadienoate ( ). To a solution of
-16 (0.06 g, 0.0826 mmol) in CH2Cl2–MeOH (3:1,
1
b
9) Schmidt, R. R. and Stumpp, M., Synthese von 1-
9 ml) was added thiourea derivative 18 (0.12 g,
0.826 mmol) at r.t. After stirring for 20 h at r.t., the
reaction mixture was concentrated in vacuo and
puriˆed by neutral silica gel chromatography
＝
thioglycosiden. Liebigs Ann. Chem.
(1983).
, 1249–1256
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The synthesis of oligoribonucleotides. Part XI.
(CHCl3:MeOH 10:1) in
a
Sephadex} LH-20
Preparation of ribonucleoside 2?-acetal 3?-esters by
column to give 0.0226 g (79
z
) of 1 as a colorless oil.
29
selective deacylation. J. Chem. Soc., Perkin Trans. I
934–942 (1975).
,
[
a
]
+4.59
9
(c
0.165, MeOH). IR nmax (ˆlm) cm„1
:
D
3389 (br.s), 2925 (m), 1739 (s), 1633 (m), 1455 (m),
1
11) Kawai, A., Hara, O., Hamada, Y., and Shioiri, T.,
Stereoselective synthesis of the hydroxy amino acid
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1169 (m), 1075 (s), 705 (w). H-NMR
d (MeOH-d4,
＝
300 MHz): 1.04 (3H, d,
CH3-7), 2.26 (1H, ddd,
J
J
6.9, CH3-2), 1.63 (3H, s,
＝
7.5 and 15.0, H-3a), 2.39
Bacillus pumilus AI-77. Tetrahedron Lett.
6331–6334 (1988).
, 29,
＝
(1H, ddd,
H-2), 3.18–3.90 (6H, H-2
6a ), 3.84 (2H, s, H-8), 5.34 (1H, d,
5.52 (1H, dt,
J
7.5 and 15.0, H-3b), 2.45 (1H, m,
, H-3 , H-4 , H-5 , H-
7.9, H-1 ),
?
?
?
＝
?
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?b
?
J
?
＝
＝
7.5 and 15.0, H-4), 5.90 (1H, d, J
J
10.7 and 15.0, H-6), 6.24 (1H, dd, J 10.7, H-5).
＝
HRFABMS m z 345.1547 (calcd. for C16 H25O8,
W
345.1549).
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Acknowledgments
We are grateful to Dr. J. Hasegawa of
Kanegafuchi Chemical Industry Co. Ltd. for kind
supplying
methyl
(S)-(+)-3-hydroxy-2-methyl-
propanoate. We thank Y. Tominaga for measuring
of high-resolution FAB mass spectrum. This work

748
H. SHIMIZU and T. KITAHARA
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,
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