4456
K. Iino et al. / Tetrahedron Letters 53 (2012) 4452–4456
the glucose derivative 28 in good yield and the manno-derivative
26, 64% and 15% yields, respectively (26; Rf 0.23, 28; Rf 0.30, hex-
ane/EtOAc, 7:3). The manno derivative was recycled. Finally, we
proceeded to the assembly of the hexasaccharide derivative. The
coupling of 9 with 28 was achieved by the action of AgOTf to afford
the hexasaccharide 29, which was isolated as a single isomer in
quantitative yield. Removal of the acetyl group afforded 30. Inver-
sion of the C-2 hydroxyl group of 30 to gluco-configuration using
oxidation–reduction procedure preferentially gave the glucose
derivative 32 (the ratio of Glc:Man, 7:1). The reaction mixture
was purified by conventional column chromatography (30; Rf
0.28, 32; Rf 0.46, toluene/EtOAc, 7:1) to give 32 in 64% yield (two
steps).
The hexasaccharide 32 and the pentasaccharide 28 were depro-
tected by conventional means and the hexasaccharide derivative
was obtained in 59% yield (Scheme 5). A Dansyl group was then
introduced for use in the detection of enzyme activities providing
1 in 85% yield. The pentasaccharide 28 was converted into 2 in
44% yield (two steps). The 1H NMR spectrum of 1 and 2 were in
good agreement with the data reported for closely related com-
pounds (Fig. 3).8,15
article, Mr. Y. Arai and S. Chiku for their contribution of this work,
and Ms. K. Kobayashi for her technical assistance.
References and notes
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3129; (b) Matsuo, I.; Totani, K.; Tatami, A.; Ito, Y. Tetrahedron 2006, 62, 8262–
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Lichtenthaler, FW.; Lergenmuller, M.; Peters, S.; Varga, Z. Tetrahedron:
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The enzymatic activity of processing
Aspergillus brasiliensis ATCC 96426a was measured using 1 as shown
in Figure 4. A reaction mixture containing 2 g of -glucosidase I,
46 nmol of 1, in PBS buffer (pH 7.0) was incubated for 30 min.
The HPLC profile of the hydrolysis reaction showed that 80% of 1
had been hydrolyzed to diglucosylated pentasaccharide 2 as
indicated by a shift in retention time.
a-glucosidase I from
l
a
In conclusion, facial construction of the tri-glucoside residue
was established using (1) the anomeric effect and neighboring-
group participation assisted stereoselective
oxidation of the C-2 hydroxyl group and (3) reduction of the corre-
sponding 2-keto group to the desired -gluco-configuration.
a-mannosylation, (2)
a
14. Reaction of using tetra-O-benzyl thioglycoside derivative under MeOTf
Regarding the stereoselectivity of the hydride reduction toward
ulosyl derivatives, our results have been inconsistent to previous
reports.9a–d A more systematic study of the reduction is in
progress. Using our strategy, the fluorescence-labeled hexasaccha-
ride substrate for processing a-glucosidase I was successfully syn-
thesized. In addition, the Dansyl group labeled hexasaccharide
conditions afforded
a mixture of a and b isomer (a/b = 3/1): Matsuo, I.;
Wada, M.; Manabe, S.; Yamaguchi, Y.; Otake, K.; Kato, K.; Ito, Y. J. Am. Chem. Soc.
2003, 125, 3402–3403.
15. Physical data for 1 and 2 are given below. 1H NMR spectra were measured on a
JEOL ECS-600 spectrometer. MALDI-TOF MS spectra were recorded in the
positive ion mode on an AXIMA Performance (Shimazu/KRATOS) equipped
with nitrogen laser with an emission wavelength of 337 nm. 2,5-
Dihydroxybenzoic acid (10 mg dissolved in 1 mL of 50/50 (v/v) acetonitrile/
water with 0.1% TFA) was used as matrix; 1: 1H NMR (600 MHz, D2O, 18 °C): d
8.49 (d, 1H, J = 8.7 Hz), 8.27 (d, 1H, J = 8.7 Hz), 8.23 (d, 1H, J = 7.2 Hz), 7.68 (dd,
2H, J = 8.0 Hz, J = 15.8 Hz), 7.41 (d, 1H, J = 7.6 Hz), 5.49 (d, 1H, J = 3.9 Hz), 5.22
(d, 1H, J = 3.9 Hz), 5.20 (s, 1H), 5.14 (d, 1H, J = 3.8 Hz), 4.98 (s, 1H), 4.88 (s, 1H),
4.19 (br s, 1H), 4.04 (br s, 1H), 3.30 (m, 2H), 2.96 (m, 2H), 2.86 (s, 6H, CH3 Â 2),
1.56 (m, 2H); MALDI-TOF MS calcd for C51H80N2O33SNa (M+Na)+ m/z: 1303.2,
found: 1303.1; 2: 1H NMR (600 MHz, D2O, 18 °C): d 8.49 (d, 1H, J = 7.9 Hz), 8.27
(d, 1H, J = 8.5 Hz), 8.23 (d, 1H, J = 8.3 Hz), 7.68 (dd, 2H, J = 8.3 Hz, J = 16.7 Hz),
7.41 (d, 1H, J = 8.1 Hz), 5.31 (d, 1H, J = 3.8 Hz), 5.22 (d, 1H, J = 3.9 Hz), 5.20 (s,
1H), 4.98 (s, 1H), 4.88 (br s, 1H), 4.19 (m, 1H), 4.03 (m, 1H), 3.97 (m, 1H), 3.30
(m, 2H), 2.96 (m, 2H), 2.86 (s, 6H, CH3 Â 2), 1.55 (m, 2H); MALDI-TOF MS calcd
for C45H70N2O28SNa (M+Na)+ m/z: 1141.4, found: 1140.9.
derivative was demonstrated to act as a substrate for processing
a-glucosidase I from A. brasiliensis ATCC 9642. A detailed investiga-
tion of the relative rates of cleavage of processing -glucosidase I is
a
currently underway, and results will be reported in due course.
Acknowledgments
A part of this work was financially supported by a Grant-in-Aid
for Scientific Research (21580410) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan and ERATO JST
and Mizutani Foundation Research Grant (2009). We gratefully
thank Dr. R. Walton for his helpful discussion in completing this