A facile synthesis of neosaccharides: 2,6′-and 3,6′-ether- linked sugars

Article abstract of DOI:10.1055/s-2006-926434

A novel synthesis of the 2,6′-O-linkage of methyl α-D-glucoside and methyl α-D-mannoside was developed based on an acetalization- reduction approach. Utilizing this approach, the 3,6′-O-linkage of methyl α-D-glucosides was also obtained. It is noteworthy

Full text of DOI:10.1055/s-2006-926434

PAPER
1415
A Facile Synthesis of Neosaccharides: 2,6¢-and 3,6¢-Ether-Linked Sugars
A
F
acile Synthesis
i
of
N
eo
d
saccharide
s
eyo Takahashi, Haruhiko Mitsuzuka, Kazusa Nishiyama, Shiro Ikegami*
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
Fax +81(426)851870; E-mail: shi-ike@pharm.teikyo-u.ac.jp
Received 28 September 2005; revised 10 November 2005
BnO
OH
OMe
O
Abstract: A novel synthesis of the 2,6¢-O-linkage of methyl a-D-
OMe
O
OBn
OBn
O
BnO
BnO
BnO
glucoside and methyl a-D-mannoside was developed based on an
acetalization–reduction approach. Utilizing this approach, the 3,6¢-
O-linkage of methyl a-D-glucosides was also obtained. It is note-
worthy that the reductive etherification of secondary alcohols and
the C6-aldehyde of carbohydrates proceeded efficiently.
OBn
5
OMe
TMSOTf
OBn
OMe
OBn
O
O
CH2Cl2 (0.2 M),
0 °C, 20 min
OHC
BnO
BnO
O
BnO
O
BnO
BnO
BnO
OMe
92%
Key words: carbohydrate, acetals, ethers, reductions, regioselec-
tivity
1
6
Scheme 2 Acetalization of aldehyde 1 with alcohol 5 catalyzed by
TMSOTf.
Since coyolosa was isolated as the first 6,6¢-ether-linked
pyranose,1 its unique structure2 along with its strong hy-
poglycemic activity prompted us to develop an efficient
method to link sugars via ether bonds.3 Recently, we re-
ported an efficient synthesis of 6,6¢-ether-linked pyra-
noses utilizing an acetalization–reduction approach
(Scheme 1).4
D-mannoside 5.6 An excess amount of a-D-mannoside 5
was reacted with 1 in the presence of three equivalents of
TMSOTf to give the acetal derivative 6 in excellent yield.
It is noteworthy that the axial C2-OH reacted smoothly to
form the relatively stable acetal, which was easily separat-
ed by silica gel column chromatography. We next exam-
ined the reduction step. Initial attempts to reduce the
acetal 6 with triethylsilane (TESH) in the presence of
TMSOTf provided the desired ether-linked sugar 7 in
moderate yield, reactions at the anomeric positions result-
ed in complicated byproducts (Table 1, entry 3). We rea-
soned that the bulky TESH barely attacked the crowded
C6-acetal, which was composed of two secondary alco-
hols, but reduced less crowded anomeric acetals. This ra-
tionalization led us to examine various reducing agents.
While the reaction with an excess amount of LiAlH4–
AlCl3 or BH3·THF–TMSOTf did not proceed,
BH3·SMe2–TMSOTf produced 7 in 51% yield. Although
borane reagents appeared hopeful, further improvement
was not achieved, and we reconsidered the reductive
cleavage with alkylsilane reagents.
In this method, the C6-aldehyde of 1 reacted with the C6-
alcohol of 2 under mild acid-catalyzed conditions to give
the intermediate acetal derivative 3, which was succes-
sively reduced to furnish 6,6¢-ether-linked pyranosides
(neo-6,6¢-O-saccharides); a one-pot reductive ether-
ification5 was also established.
HO
OMe
O
O
O
BnO
BnO
O
O
acetalization
OMe
BnO
BnO
OBn
BnO
BnO
OBn
BnO
BnO
2
BnO
O
OMe
OHC
BnO
BnO
BnO
3
OMe
O
BnO
reduction
OMe
1
OMe
O
6
O
one-pot reductive etherification
As shown in Table 1, the reaction with bulky triphenylsi-
lane and triisopropylsilane gave mixtures of unidentified
products with an excess amount of 5, which may be attrib-
uted to over-reduction of the acetal carbon (Table 1, en-
tries 1 and 2). This over-reduction means that both acetal
bonds are cleaved simultaneously by the bulky silane to
give two equivalents of 5.7 The less hindered diethylmeth-
ylsilane (DEMSH), dimethylethylsilane (DMESH), and
trimethylsilane (TMSH) reacted well (Table 1, entries 4,
6, and 8), but the use of diethylsilane (DESH) proved to
be less effective. Under optimized conditions, acetal 6
was treated with DMESH (14.4 equiv) in the presence of
TMSOTf (4.8 equiv) at –20 °C for two hours to afford the
2,6¢-ether-connected sugar 7 in 83% yield (Table 1, entry
7).
6'
BnO
OBn
BnO
O
OBn
BnO
BnO
4
OMe
Scheme 1 Synthesis of the neo-6,6¢-O-saccharide 4.
Such successful results led us to pursue the prospect of
achieving a novel connection between a secondary alco-
hol (C2, C3) and the aldehyde (C6) of pyranosides via ac-
etalization–reduction.
We applied the previous procedure to the acetalization of
the C6-aldehyde 1 and the secondary alcohol of methyl a-
SYNTHESIS 2006, No. 9, pp 1415–1418
x
x
.
x
x
.2
0
0
6
Advanced online publication: 11.04.2006
DOI: 10.1055/s-2006-926434; Art ID: F16305SS
© Georg Thieme Verlag Stuttgart · New York
Having established a method for the connection of the al-
dehyde of 1 to the secondary alcohol 5, we then examined

1416
H. Takahashi et al.
PAPER
Table 1 Reduction of Acetal 6a
OMe
OBn
OBn
OMe
OMe
O
OBn
OBn
BnO
O
TMSOTf
reducing reagent
O
2
OBn
OBn
OMe
BnO
BnO
OH
O
OBn
O
O
OBn
O
O
6'
+
BnO
BnO
BnO
O
BnO
BnO
OMe
5
BnO
BnO
OMe
7
6
Entry
Reagent
Time (h)
Yield of 7 (%)b
Yield of 5 (%)c
1
2
3
4
5
6
7d
8
triphenylsilane
triisopropylsilane
TESH
4
0
0
156
145
104
96
4
4
53
73
47
78
83
70
DEMSH
4.5
3
DESH
100
97
DMESH
2.5
2
DMESH
107
108
TMSH
3
a Reagents: the substrate was treated with TMSOTf (4.8 equiv) and silane reagent (9.6 equiv) in CH2Cl2 at –20 °C.
b Isolated yield.
c Isolated yield of 5 based on 6.
d DMESH (14.4 equiv) was used.
the acetalization of 1 with methyl a-D-glucoside 88 tions. Reaction of aldehyde 1 with diol 8 (10 equiv) at
(Scheme 3). In this case a cyclic acetal should form, how- high dilution (0.005 M) afforded the desired cyclic acetal
ever, one potential issue was the regioselectivity of the re- 9 in 56% yield. It had been anticipated that the cyclic ac-
duction of the cyclic acetal, which might afford the ether- etal derivative 9, which was composed of a 2,3-trans-diol,
linked sugars as a mixture of regioisomers.
would be unstable. However, we found that 9 was so sta-
ble that it could be isolated.9
BnO
BnO
BnO
BnO
O
O
BnO
BnO
HO
BnO
BnO
O
TMSOTf (2.0 equiv)
O
HO
O
O
8
O
TMSOTf (3.0 equiv)
TESH (20.0 equiv)
OMe
OMe
CH2Cl2
0 °C, 30 min
O
O
3
OMe
O
HO
BnO
BnO
OMe
6'
CH2Cl2 (0.05 M)
O
O
OHC
BnO
BnO
BnO
BnO
BnO
BnO
(0.1 M): 32%
(0.05 M): 41%
(0.005 M): 56%
BnO
O
OMe
9
–78 °C, 18.5 h: 5%
–40 °C, 17 h: 55%
–20 °C, 7 h: 45%
BnO
BnO
OMe
OMe
BnO
OMe
1
9
10
Scheme 3 Synthesis of the cyclic acetal 9.
Scheme 4 Regioselective reduction of the cyclic acetal 9 with
TESH–TMSOTf.
Initially we looked at the formation of the cyclic acetal 9.
Reaction of one of the hydroxyl groups of the 2,3-diol 8
with the C6-aldehyde of 1 furnishes a hemi-acetal. The
second step, formation of the desired cyclic acetal, is not
a simple task. There are two possible acetals which can
form: the desired cyclic acetal 9, which would result from
intramolecular attack of the remaining hydroxyl group on
the hemi-acetal or a non-cyclic acetal which would result
from attack of a second molecule of 8 on the hemi-acetal.
We focused on the concentration of the solution as we
wished to avoid intermolecular acetalization. While inter-
molecular acetal formation proceeded under the usual
conditions (0.1 M solution), it was found that intramolec-
ular acetalization dominated under more dilute condi-
Reduction of the acetal using TESH–TMSOTf was then
examined (Scheme 4). The reaction proceeded very slow-
ly at –78 °C, although we were delighted to find the 3,6¢-
ether-linked sugar 10 as the sole product. At –40 °C, re-
duction of the cyclic acetal 9 proceeded with specific
cleavage of the 2,6¢ connection, giving the 3,6¢-ether-
linked sugar 10 in 55% yield.10 Unfortunately, an attempt
to reduce the cyclic acetal at –20 °C resulted in over-re-
duced mixtures, which decreased the yield of 10. It should
be noted that a 2,6¢-ether-linked sugar has never been ob-
served even at high temperatures. Although there is limit-
ed information on the specificity for the 3,6¢-ether-linked
sugar, Hung et al. reported similar results: the 2,3-O-ben-
Synthesis 2006, No. 9, 1415–1418 © Thieme Stuttgart · New York

PAPER
A Facile Synthesis of Neosaccharides
1417
over Na2SO4, filtered, and the solvent was removed in vacuo. The
residual oil was initially purified by chromatography (toluene–
EtOAc, 3:1) and the excess of 5 was recovered (372 mg, 0.801
mmol). Further chromatographic purification (toluene–i-Pr2O, 2:3)
of the remaining material afforded 6 (141 mg, 0.102 mmol, 92%);
[a]D19 +3.39 (c 0.84, CHCl3).
1H NMR (600 MHz, CDCl3): d = 7.32–7.11 (m, 45 H), 5.11 (d,
J = 11.3 Hz, 1 H), 5.03 (s, 1 H), 4.98 (d, J = 1.7 Hz, 1 H), 4.87 (d,
J = 10.4 Hz, 1 H), 4.84 (d, J = 10.5 Hz, 1 H), 4.76–4.70 (m, 5 H),
4.65–4.63 (m, 3 H), 4.59 (d, J = 12.1 Hz, 1 H), 4.56–4.47 (m, 6 H),
4.44 (d, J = 10.7 Hz, 1 H), 4.28 (d, J = 11.8 Hz, 1 H), 4.17 (d,
J = 11.8 Hz, 1 H), 3.99–3.94 (m, 2 H), 3.91 (dd, J = 9.6, 9.6 Hz, 1
H), 3.85–3.83 (m, 3 H), 3.74–3.68 (m, 6 H), 3.63 (d, J = 10.2 Hz, 1
H), 3.40–3.38 (m, 2 H), 3.24 (s, 3 H), 3.23–3.22 (6 H, m).
zylidene acetal of methyl a-D-glucoside was reduced by
TMSOTf–TESH regioselectively to give the 3-O-benzyl
product.11 We postulate that the 2,6¢-acetal bond is more
reactive than the 3,6¢-acetal bond, also the C2-alcohol of
methyl a-D-glucoside may be influenced by the a-meth-
oxy group at the anomeric position which decreases its
nucleophilicity and hence the 2,6¢-acetal bond would be
cleaved.
BnO
TMSOTf
BnO
O
(10.0 equiv)
TESH
BnO
HO
O
BnO
O
HO
(10.0 equiv)
TfOH
3
8
OMe
HO
6'
TMSOTf
(2.0 equiv)
OMe
O
BnO
BnO
13C NMR (150 MHz, CDCl3): d = 139.6, 138.7, 138.6, 138.5, 138.3,
138.2, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.5, 127.4,
127.3, 127.2, 126.8, 110.6, 103.0, 100.1, 98.0, 82.0, 79.9, 79.4,
78.0, 77.2, 76.0, 75.9, 75.6, 75.5, 75.1, 75.0, 74.4, 73.5, 73.4, 73.2,
73.1, 72.2, 72.0, 71.7, 69.6, 69.3, 55.3, 54.8, 54.4.
(2.0 equiv)
OHC
BnO
BnO
O
CH2Cl2
0 °C, 1 h
CH2Cl2
BnO
OMe
–20 °C, 4 h
BnO
10
OMe
1
29%
Scheme 5 One-pot acetalization–reduction of the aldehyde 1 with
the diol 8 using TESH in the presence of TMSOTf–TfOH.
HRMS (FAB-NBA, NaI): m/z calcd for C84H92O17Na: 1395.6232;
found: 1395.6250.
Compound 7
The one-pot etherification of aldehyde 1 with diol 8 was
further examined. Acetalization in the presence of TMS-
OTf was carried out at 0 °C for one hour, and subsequent
addition of TESH and TMSOTf to this system converted
the acetal into 10 in 19% yield. Surveying the conditions,
To a solution of 6 (50 mg, 0.0364 mmol) in CH2Cl2 (0.49 mL) was
added TMSOTf (31.7 mL, 0.175 mmol) and DMESH (69.2 mL,
0.524 mmol) successively at –78 °C. The resulting solution was
stirred for 2 h at –20 °C. The reaction was quenched with a sat. aq
solution of NaHCO3 (30 mL) and extracted with CH2Cl2 (200 mL).
we found that the addition of TfOH to this system provid- The combined organic phase was dried over Na2SO4, filtered, and
the solvent was removed in vacuo. The residual oil was initially pu-
ed a better result (29%). Although the effect caused by the
combination of Lewis acid and Brönsted acid12 in this sys-
rified by chromatography (toluene–EtOAc, 4.5:1) and the excess of
5 was recovered (18.1 mg, 0.0389 mmol). Chromatographic purifi-
tem was not fully explained, it might be useful for the de-
velopment of other reaction systems.
cation (toluene–EtOAc, 15:1) of the remaining material afforded 7
(27.5 mg, 0.0302 mmol, 83%); [a]D20 +3.02 (c 0.84, CHCl3).
1H NMR (600 MHz, CDCl3): d = 7.36–7.04 (m, 30 H), 4.95 (d,
J = 10.7 Hz, 1 H), 4.83–4.77 (m, 5 H), 4.72–4.68 (m, 2 H), 4.65–
4.62 (m, 3 H), 4.54 (d, J = 3.6 Hz, 1 H), 4.49 (d, J = 12.1 Hz, 1 H),
4.35–4.31 (m, 2 H), 3.96 (dd, J = 9.5, 9.1 Hz, 1 H), 3.90 (dd, J = 9.6,
9.3 Hz, 1 H), 3.86 (dd, J = 9.6, 2.8 Hz, 1 H), 3.78 (dd, J = 2.8, 1.9
Hz, 1 H), 3.75–3.64 (m, 6 H), 3.51 (dd, J = 9.5, 3.6 Hz, 1 H), 3.33
(s, 3 H), 3.31 (s, 3 H).
13C NMR (150 MHz, CDCl3): d = 138.9, 138.4, 138.2, 128.4, 128.3,
128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 99.9, 98.2,
82.1, 80.9, 79.9, 77.7, 77.6, 75.7, 75.1, 75.0, 73.5, 73.3, 72.4, 71.7,
71.2, 70.6, 69.2, 55.1, 54.6.
In conclusion, we have established a novel and efficient
method for the synthesis of 2,6¢-ether-linked sugars based
on reductive etherification using TMESH as the reducing
agent. We also developed the acetalization of the 2,3-diol
and the C6-aldehyde of pyranoside and its regioselective
reductive cleavage to produce a 3,6¢-ether-linked sugar.
This is the first application of the reductive etherification
of secondary alcohols and the C6-aldehyde in pyrano-
sides. Work concerning the connection of other sugars by
an ether linkage using similar concepts is in progress.
HRMS (FAB-NBA, NaI): m/z calcd for C56H62O11Na: 933.4190;
Melting points were determined with a Yanagimoto micro melting
point apparatus and were uncorrected. IR spectra were measured
with a JASCO FT/IR-8000 spectrometer. HRMS-FAB were taken
with a JEOL SX-102A. 1H NMR and 13C NMR spectra were record-
ed at 600 MHz with a JEOL GSX-600 spectrometer using TMS as
an internal standard. Chemical shifts were reported in ppm down-
field from TMS. Optical rotations were measured on a JASCO DIP-
370 in a 1-dm cell. Analytical and preparative TLC was conducted
on pre-coated TLC plates (silica gel 60 F254, Merck). Column chro-
matography was performed using Merck silica gel 60N (100–210
mm). All anhydrous solvents were purified according to standard
methods.
found: 933.4185.
Compound 9
To a mixture of 1 (500 mg, 1.08 mmol) and 8 (4.04 g, 10.8 mmol)
in CH2Cl2 (216 mL) was added TMSOTf (392 mL, 2.16 mmol) at
0 °C. The resulting solution was stirred for 30 min. The reaction
was quenched with a sat. solution of NaHCO3 (30 mL) and extract-
ed with CH2Cl2 (200 mL). The combined organic phase was dried
over Na2SO4, filtered, and the solvent was removed in vacuo. The
residual oil was initially purified by chromatography (toluene–
EtOAc, 2:1) and the excess of 8 was recovered. Chromatographic
purification (hexane–Et2O, 3:2) of the remaining material afforded
9 (497 mg, 0.607 mmol, 56%); [a]D17 +87.7 (c 1.12, CHCl3).
1H NMR (600 MHz, CDCl3): d = 7.39–7.23 (m, 25 H), 5.55 (d,
J = 1.6 Hz, 1 H), 5.11 (d, J = 3.0 Hz, 1 H), 4.98 (d, J = 10.9 Hz, 1
H), 4.87 (d, J = 10.7 Hz, 1 H), 4.83 (d, J = 10.9 Hz, 1 H), 4.81 (d,
J = 12.4 Hz, 1 H), 4.80 (d, J = 11.4 Hz, 1 H), 4.71 (d, J = 12.4 Hz,
1 H), 4.65 (d, J = 3.7 Hz, 1 H), 4.64 (d, J = 10.7 Hz, 1 H), 4.61 (d,
J = 12.2 Hz, 1 H), 4.54 (d, J = 11.4 Hz, 1 H), 4.50 (d, J = 12.2 Hz,
Compound 6
To a mixture of 1 (51.3 mg, 0.11 mmol) and 5 (517 mg, 1.11 mmol)
in CH2Cl2 (0.56 mL) was added TMSOTf (60.5 mL, 0.334 mmol) at
0 °C. The resulting solution was stirred for 20 min. The reaction
was quenched with a sat. solution of NaHCO3 (30 mL), and extract-
ed with CH2Cl2 (200 mL). The combined organic phase was dried
Synthesis 2006, No. 9, 1415–1418 © Thieme Stuttgart · New York

1418
H. Takahashi et al.
PAPER
1 H), 4.06 (dd, J = 9.6, 9.5 Hz, 1 H), 3.99 (dd, J = 9.5, 9.3 Hz, 1 H),
3.87 (dd, J = 9.5, 9.4 Hz, 1 H), 3.82 (dd, J = 10.2, 1.6 Hz, 1 H), 3.76
(dd, J = 10.7, 3.8 Hz, 1 H), 3.71 (dd, J = 10.7, 2.2 Hz, 1 H), 3.64–
3.61 (m, 3 H), 3.53 (dd, J = 9.5, 3.7 Hz, 1 H), 3.46 (s, 3 H), 3.40 (s,
3 H).
13C NMR (150 MHz, CDCl3): d = 138.6, 138.1, 137.9, 128.4, 128.3,
128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 103.0, 97.8, 97.6, 82.1,
79.8, 79.2, 78.5, 75.9, 75.8, 75.6, 75.1, 73.5, 73.2, 72.6, 71.4, 70.0,
68.1, 55.5, 54.9.
Acknowledgment
We wish to thank Miss J. Shimode and Miss A. Tonoki for spectro-
scopic measurements. This work was partially supported by a
Grant-in-Aid for Scientific Research from the Japan Society for the
Promotion of Science. Support from the Takeda Science Foundati-
on, Uehara Memorial Foundation and the Research Foundation for
Pharmaceutical Sciences to H.T. are gratefully acknowledged.
References
HRMS (FAB-NBA, NaI): m/z calcd for C49H54O11Na: 841.3522;
found: 841.3543.
(1) Pérez, S.; Pérez, G. R. M.; Pérez, G. C.; Zavala, G. M. A.;
Vargas, S. R. Pharm. Acta Helv. 1997, 72, 105.
(2) We propose here that the sugars which are not linked by
anomeric linkages should be called ‘neo-saccharides’. Thus
the 6,6¢-ether-linked sugar should be called a ‘neo-6,6¢-O-
saccharide’.
(3) Hains also independently reported the synthesis of 6,6¢-
ether-linked sugars, see: (a) Hains, A. H. Tetrahedron Lett.
2004, 45, 835. (b) Hains, A. H. Org. Biomol. Chem. 2004, 2,
2352.
Compound 10
To a solution of 9 (37.0 mg, 0.0452 mmol) in CH2Cl2 (0.90 mL) was
added TMSOTf (24.6 mL, 0.136 mmol) and TESH (144 mL, 0.904
mmol) successively at –78 °C. The resulting solution was stirred for
17 h at –40 °C. The reaction was quenched with a sat. solution of
NaHCO3 (30 mL) and extracted with CH2Cl2 (200 mL). The com-
bined organic phase was dried over Na2SO4, filtered, and the solvent
was removed in vacuo. The residual oil was purified by chromatog-
raphy (toluene–EtOAc, 3:1) to afford 10 (20.3 mg, 0.0247 mmol,
55%).
(4) Takahashi, H.; Fukuda, T.; Mitsuzuka, H.; Namme, R.;
Miyamoto, H.; Ohkura, Y.; Ikegami, S. Angew. Chem. Int.
Ed. 2003, 42, 5069.
One-Pot Synthesis of 10
(5) (a) Doyle, M. P.; Debruyn, D. J.; Donnelly, S. J.; Kooistra,
D. A.; Odubela, A. A.; West, C. T.; Zonnebelt, S. M. J. Org.
Chem. 1974, 39, 2740. (b) Sassaman, M. B.; Prakash, G. K.;
Olah, G. A. Tetrahedron 1988, 44, 3771. (c) Kato, J.-I.;
Iwasawa, N.; Mukaiyama, T. Chem. Lett. 1985, 743.
(d) Hatakeyama, S.; Mori, H.; Kitano, K.; Yamada, H.;
Nishizawa, M. Tetrahedron Lett. 1994, 35, 4367.
(e) Suzuki, T.; Ohashi, K.; Oriyama, T. Synthesis 1999,
1561. (f) Lee, S. H.; Park, Y. J.; Yoon, C. M. Tetrahedron
Lett. 1999, 40, 6049. (g) Miura, K.; Ootsuka, K.; Suda, S.;
Nishikiori, H.; Hosomi, A. Synlett 2002, 313. (h)Wada,M.;
Nagayama, S.; Mizutani, K.; Hiroi, R.; Miyoshi, N. Chem.
Lett. 2002, 248.
To a mixture of 1 (40.0 mg, 0.087 mmol) and 8 (324 mg, 0.87
mmol) in CH2Cl2 (1.73 mL) was added TMSOTf (31.3 mL, 0.17
mmol) at 0 °C. The resulting solution was stirred for 1 h and then
TMSOTf (157 mL, 0.87 mmol), TESH (138 mL, 0.87 mmol), and
TfOH (15.3 mL, 0.17 mmol) were added successively at –78 °C. Af-
ter stirring at –20 °C for 4 h, the reaction was quenched with a sat.
solution of NaHCO3 (30 mL), and extracted with CH2Cl2 (200 mL).
The combined organic phase was dried over Na2SO4, filtered, and
the solvent was removed in vacuo. The residual oil was purified by
chromatography (toluene–Et2O, 1:1) to afford 10 (20.9 mg, 0.0255
mmol, 29%); [a]D20 +58.7 (c 0.95, CHCl3).
1H NMR (600 MHz, CDCl3): d = 7.35–7.05 (m, 25 H), 4.96 (d,
J = 11.0 Hz, 1 H), 4.87 (d, J = 11.0 Hz, 1 H), 4.81–4.79 (m, 2 H),
4.77 (d, J = 12.1 Hz, 1 H), 4.73 (d, J = 10.9 Hz, 1 H), 4.68 (d,
J = 3.6 Hz, 1 H), 4.66–4.63 (m, 3 H), 4.50 (d, J = 12.1 Hz, 1 H),
4.44 (d, J = 10.9 Hz, 1 H), 4.33 (dd, J = 11.8, 2.2 Hz, 1 H), 3.97 (dd,
J = 9.4, 8.8 Hz, 1 H), 3.88 (dd, J = 11.8, 2.2, Hz 1 H), 3.77–3.71 (m,
4 H), 3.69–3.65 (m, 3 H), 3.56–3.54 (m, 2 H), 3.41 (s, 3 H), 3.35 (s,
3 H).
(6) Franks, N. E.; Montgomery, R. Carbohydr. Res. 1968, 6,
268.
(7) We have no definite information on this over-reduction
because the reaction was not clean. We abandoned further
investigation of this reduction with bulky silanes.
(8) Fu, X.; Kong, F.; Lu, D.; Li, G. Carbohydr. Res. 1992, 235,
163.
(9) The cyclic acetal composed of pyranosides was
unexpectedly stable. Further investigations to employ such
connections in the novel linkage of sugars are currently
underway in our laboratory.
(10) The stereochemical outcome was accurately determined
from the NMR spectrum of its acetate.
13C NMR (150 MHz, CDCl3): d = 138.7, 138.1, 138.0, 137.9, 128.5,
128.4, 128.3, 128.0, 127.9, 127.7, 127.6, 127.5, 99.2, 98.2, 86.1,
81.8, 80.2, 77.3, 75.7, 75.1, 74.7, 73.5, 72.8, 71.5, 71.0, 70.3, 68.5.
HRMS (FAB-NBA, NaI): m/z calcd for C49H56O11Na: 843.3720;
found: 843.3726.
(11) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Fan, H.-F.; Pai, C.-L.;
Yang, W.-C.; Lu, L.-D.; Hung, S.-C. Angew. Chem. Int. Ed.
2002, 41, 2360.
(12) Yamamoto, H.; Futatsugi, K. Angew. Chem. Int. Ed. 2005,
44, 1924.
Synthesis 2006, No. 9, 1415–1418 © Thieme Stuttgart · New York