Stereoselective tris-glycosylation to introduce β-(1→3)-branches into gentiotetraose for the concise synthesis of phytoalexin-elicitor heptaglucoside

Article abstract of DOI:10.1039/b800809d

Dodecyl thioglycosides (3, 4, 5) were prepared by conventional transformation of d-glucose and used as new glycosyl donors for a short-step synthesis of phytoalexin elicitor heptaglucoside. A gentio-tetraoside derivative (6) having three hydroxyl groups was synthesized by NIS-TfOH promoted glycosylate in more than 90% yield followed by selective removal of temporary protective groups. Undesired formation of α-glycosides at the introduction of β-(1→3)-branches into gentio-oligosaccharides was found to be suppressed by use of a thiophilic reagent system, BSP (1-benzenesulfinyl piperidine)-Tf₂O, giving the heptaglucoside in only four glycosylation steps. The Royal Society of Chemistry.

Full text of DOI:10.1039/b800809d

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Stereoselective tris-glycosylation to introduce b-(1→3)-branches into
gentiotetraose for the concise synthesis of phytoalexin-elicitor heptaglucoside†
Sang-Hyun Son, Chiharu Tano, Jun-ichi Furukawa, Tetsuya Furuike and Nobuo Sakairi*
Received 16th January 2008, Accepted 25th January 2008
First published as an Advance Article on the web 22nd February 2008
DOI: 10.1039/b800809d
Dodecyl thioglycosides (3, 4, 5) were prepared by conventional transformation of D-glucose and used as
new glycosyl donors for a short-step synthesis of phytoalexin elicitor heptaglucoside. A
gentio-tetraoside derivative (6) having three hydroxyl groups was synthesized by NIS–TfOH promoted
glycosylate in more than 90% yield followed by selective removal of temporary protective groups.
Undesired formation of a-glycosides at the introduction of b-(1→3)-branches into
gentio-oligosaccharides was found to be suppressed by use of a thiophilic reagent system, BSP
(1-benzenesulfinyl piperidine)–Tf2O, giving the heptaglucoside in only four glycosylation steps.
Introduction
Since Albersheim et al. identified a heptaglucoside analogous
to 1 that elicits production of phytoalexin in soybeans,1 its
unique structure has often been used as a model compound to
demonstrate the feasibility of new methodologies in chemical
synthesis of oligosaccharides, e.g., convergent block synthesis, one-
pot sequential glycosylation, and chemoselective glycosylation.2
Compound 1 consists of a b-(1→6)-linked D-glucopyranose
backbone (gentiopentaose unit) and two b-(1→3)-linked branches
(laminaribiose units). Because of the difficulty of glycosylating
the sterically hindered 3-hydroxyl group, the most successful
syntheses of 1 reported to date involved construction of the
laminaribiose units at an earlier stage of the synthetic scheme.
In contrast to this laminaribiose route, van Boom et al. proposed
a seemingly straightforward strategy, in which the b-(1→6)-linked
backbone of 1 would be synthesized first and two b-(1→3)-linked
branches would be introduced subsequently.3 However, no one has
reported the total synthesis of 1 via this gentio-oligosaccharide
route. Recently, while investigating the regioselective introduction
of a b-(1→3)-linked branch into gentio-oligosaccharides using
our newly-developed dodecyl thioglycoside donors,4 we found that
BSP–Tf2O5 was a suitable promoter for our purpose. In this paper,
we report the first successful results using this approach, which
involves tris-glycosylation of a gentiotetraose intermediate.
Results and discussion
Following the retrosynthetic analysis of the target heptaglucoside
Scheme
1
Retrosynthetic analysis of the heptaglucoside 1 by
1 proposed by van Boom, elimination of three glucose moieties
at the non-reducing end and branches leaves a b-(1→6)-linked
gentiotetraoside 6 as shown in Scheme 1.
tris-glycosylation.
Provision for further tris-glycosylation sites in 6 is anticipated
through the use of temporary protecting groups, O-chloroacetyl
(MCA) and O-allyl groups, allowing for exposure of the free
hydroxylic acceptor sites. Furthermore, participation of the neigh-
boring 2-O-benzoyl protection groups in the dodecyl thioglucosyl
donors would afford the desired b-glucosidic linkages. As a result,
the total synthesis can be initiated from a known acceptor 2 and
three dodecyl thioglycosyl donors (3, 4, 5). Starting from readily
Division of Environment Materials Science, Graduate School of Environ-
mental Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
E-mail: saka@ees.hokudai.ac.jp; Fax: +81-11-706-2257; Tel: +81-11-706-
2257
† Electronic supplementary information (ESI) available: 1H, 1H-1H COSY
and 13C NMR spectra for compounds 3, 4, 5, 6, 7, 8, 13, 14, and 1H NMR
spectrum for compound 1. See DOI: 10.1039/b800809d
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Scheme 2 Synthesis of glycosyl donor 3. Reagents and conditions: (i) C12H25SH, BF3·Et2O, (CH2)2Cl2, 0 ◦C, 87%; (ii) (a) NaOMe, MeOH, 3 h; (b)
TrCl, pyridine, DMAP, 60 ◦C, 5 h; (c) BzCl, pyridine, 60 ◦C, overnight, 91% over 3 steps; (iii) (a) AcOH–H2O = 5 : 1, 70 ◦C, 1 h; (b) (MCA)2O,
pyridine–CH2Cl2 = 1 : 10, 3 h, 92%, over 2 steps. DMAP = N, N-dimethylaminopyridine, MCA = chloroacetyl.
Scheme 3 Synthesis of glycosyl donor 4 and 5. Reagents and conditions: (i) C12H25SH, BF3·Et2O, (CH2)2Cl2, 94%; (ii) (a) NaOMe, MeOH, 3 h; (b) TrCl,
pyridine, 60 ◦C, overnight; (c) BzCl, pyridine, 0 ◦C to rt, overnight, 86% over 3 steps; (iii) (a) AcOH–H2O = 5 : 1, 70 ◦C, 1 h; (b) MCA, pyridine–CH2Cl2 =
1 : 10, 87% over 2 steps; (iv) (a) NaOMe, MeOH, 5 h; (b) BzCl, pyridine, rt, overnight, 86% over 2 steps.
available D-glucose derivatives and non-volatile l-dodecanethiol,
the glycosyl donors (3, 4, 5) were prepared by means of conven-
tional transformations as shown in Schemes 2 and 3. Using the
thioglycosides 3 and 4 as glycosyl donors, and N-iodosuccinimide
(NIS)–triflic acid (TfOH),7 as the promoter, we proceeded with
sequential glycosylation to synthesize the gentiotetraoside 6, as
outlined in Scheme 4.
Coupling 2 and the dodecylthio donor 3, which has a MCA and
an O-allyl protecting group, was first performed in dry CH2Cl2
using NIS–TfOH as a promoter, and the temporary O-MCA
protecting group was subsequently removed by treatment with
aqueous pyridine, giving the desired disaccharide acceptor 7 in
92% overall yield. Moreover, two gentiotrioses 8 and 9 were
synthesized under similar conditions with the O-MCA protected
4, and the per-benzoylated donors 5 in high yields, respectively.
The acceptor 8 was further glycosylated with 3 to give the tetraose
11 which has two O-allyl groups. Finally, selective removal of
the O-allyl groups in 9 and 11 was successfully performed by
ultrasonication with PdCl2,8 giving the acceptors 103 and 6 in 90%
yield. The triol 6, obtained in an excellent overall yield, was a
potential intermediate in our synthetic route to 1. Compound 10
was used as a model acceptor for an investigation into introducing
a b-(1→3)-linked branch.
Our attention was focused next on tris-glycosylation to intro-
duce b-D-glucose residues into 6 concurrently. As a preliminary
experiment, the triol 6 was treated with the donor 5 (3.6 equiv.)
in the presence of NIS–TfOH for 2 days. As predicted by van
Scheme 4 Synthesis of gentio-oligosaccharide intermediate. Reagents and
Boom,3 this was less successful and led to a complex mixture
conditions: (i) NIS–TfOH, CH2Cl2, −20 ◦C to rt; then H2O–pyridine,
of products, from which crude fully benzoylated heptaglucoside,
hexaoside, and gentiopentaoside were obtained in 25, 39, and
18% yields, respectively. However, 1H NMR spectra of the crude
oligosaccharide thus obtained revealed contamination of several
undesired a-glucosidic linkages.
50 ◦C, overnight, 7: 92%; (ii) NIS–TfOH, CH2Cl2, −20 ◦C to rt; then
H2O–pyridine, 50 ◦C, overnight, 4→8: 92% and 5→9: 88%; (iii) PdCl2,
NaOAc–95% AcOHaq., ultrasonication, rt, 10: 90%; (iv) NIS–TfOH,
CH2Cl2, −20 ◦C to rt; then H2O–pyridine, 50 ◦C, overnight, 11: 92%;
(v) PdCl2, NaOAc–95% AcOHaq., ultrasonication, rt, 6: 90%.
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These disappointing results forced us to seek better reaction
conditions for the introduction of the b-(1→3)-linked branches.
Using the model acceptor 10 and the disarmed donor 5, we
evaluated the recently developed promoters of thioglycosides as
shown in Scheme 5; the results are summarized in Table 1. To
our surprise, the reaction using NIS–TfOH at −40 ◦C to room
temperature in dry CH2Cl2 (entry 1) afforded 13 which was isolated
as an anomeric mixture (a : b = 1 : 1.4) in 41% yield, even though
a participating benzoyl ester is present at the C-2 position in 5.
Similarly, the well-known thioethyl counterpart 12 was also able to
provide 13 with a slightly poorer a: b ratio (entry 3). Furthermore,
we also examined milder thiophilic reagents, NIS–TfOH–AgOTf9
and ICl–AgOTf,10 for which a substoichiomeric amount of pro-
moter has been reported to activate the thioglycoside, producing
a sulfonium byproduct that can further promote glycosylations.
However, 13 was obtained in 28% yield and with disappointing
stereoselectivity (a : b = 1 : 1.4); representative reactions are
highlighted in entry 4. Although the unusual formation of 1,2-
cis-glycosides has been explained by unfavorable and mismatched
structure between a glycosyl donor and an acceptor,11 little has
been reported on b-(1→3)-linked systems. We hypothesized that
severe steric hindrance between acceptor 10 and an orthoester
intermediate derived from the donor 5 occurred in oxocarbenium
ion leading to the b-glycosidic bond, but not in the transition state
leading to the a-bond. We next focused on a BSP–Tf2O promoter
system developed by Crich et al., which is known to facilitate
formation of a highly reactive glycosyl triflate intermediate. As
shown in entries 6 and 7, BSP–Tf2O mediated condensation
between 10 and 5 proceeded with complete stereoselectivity to
yield the b-linked tetraglucoside 13 in 44% yield. Use of slightly
excess donor was more effective to yield 13 (60%). This b-
selectivity can be explained by the rapid SN2-like displacement
of the intermediate a-triflate, which has also been observed by
the groups of Crich,5,12a van der Marel,12b,c and Yoshida.12d The
satisfactory stereoselectivity and product yield of the BSP–Tf2O
mediated glycosylation made it applicable to our purpose.
Based on these fruitful results, we finally undertook the
culminating step of our synthetic scheme, the tris-glycosylation
of 6 to construct the heptaglucoside. As shown in Scheme 6,
the dodecylthio donor 5 was pre-activated with BSP–Tf2O at
◦
−78 C for 15 min, and the tetraose acceptor 6, which has three
hydroxyl groups, was subsequently added and the reaction was
completed while gradually increasing the reaction temperature
from −78 to −40 ◦C overnight. As we expected, the activation
and condensation proceeded smoothly, as monitored by two-
dimensional TLC analysis (hexane–EtOAc, 1 : 1 and toluene–
EtOAc 5 : 1, v/v). Repeated chromatography on a silica gel
column with these solvent systems furnished the fully protected
heptaglucoside 14 in 47% yield together with a mixture of
1
hexaglucosides in 42% yield. In a 600 MHz H NMR spectrum
of 14, six anomeric protons, except for one at the reducing end,
appeared as doublets with large coupling constants, suggesting all
glucosidic linkages were b in configuration. Final removal of all
benzoyl groups was performed with NaOMe in MeOH–H2O to
give known target compound 1, the 1H NMR spectrum of which
was consistent with the reported data.2c,3
Scheme 5 Model glycosylation to introduce b-(1→3)-branch.
Table 1 Evaluation of promoter system of thioglycosides in b-(1→3)-
branch formationa
Scheme 6 Synthesis of the heptaglucoside 1. Reagents and conditions: (i)
BSP–Tf2O, CH2Cl2, −78 ◦C to −40 ◦C, overnight, 14: 47%; (ii) NaOMe,
MeOH–H2O = 1 : 1, 24 h, rt, 1: 74%.
Entry
Promoter
Temperature
Yield (a : b)
1
NIS–TfOH
NIS–TfOH
NIS–TfOH
NIS–TfOH–AgOTf
ICl–AgOTf
BSP–Tf2O
−40 ◦C to rt
−40 ◦C to rt
−40 ◦C to rt
−40 ◦C to rt
−40 ◦C to rt
−78 ◦C to rt
−78 ◦C to rt
41% (1 : 1.4)
39% (1 : 1.2)
33% (1 : 1.3)
28% (1 : 1.4)
No trace
44% (b only)
60% (b only)
2b
3c
4
Conclusions
5
6
It has been shown for the first time that a concise synthesis of the
branched structure of the phytoalexin elicitor heptaglucoside 1 is
enabled by employing sulfonyl triflate mediated tris-glucosylation
of the gentiotetraose intermediate 6. Since this approach allowed
the introduction of two b-(1→3)-glucosyl branches at the final
stage of the synthesis, this strategy would be applicable to the
7c
BSP–Tf2O
a All reactions were performed with 1.2 eq. of donor in CH2Cl2. Anomeric
ratio determined by integration of the 1H NMR spectrum of the crude
reaction mixture. b Glycosyl donor 12 was used. c Donor 5 (1.5 eq.) was
used.
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synthesis of various analogues of 1 that have different mono-
and/or oligosaccharide branches.
131.1, 117.2, 84.0, 81.5, 76.8, 76.4, 73.3, 71.4, 69.8, 62.8, 32.2, 30.6,
30.1, 29.9, 29.8, 29.6, 29.4, 29.1, 22.9, 21.2, 21.1, 14.4, 11.2; Anal.
Calcd for C27H46O8S: C, 61.10; H, 8.74; S, 6.04%; Found: C, 60.96;
H, 8.75; S, 6.07%.
Experimental
Dodecyl 3-O-allyl-2,4-di-O-benzoyl-6-O-trityl-1-thio-b-
General methods
D-glucopyranoside (19)
All chemicals were purchased as reagent grade and used without
further purification whereas NIS was recrystallized by 1,4-dioxane
and diethyl ether (1 : 1, v/v) before use. Dichloromethane (CH2Cl2)
and 1,2-dichloroethane were distilled over calcium hydride. Molec-
To a solution of 18 (500 mg, 0.9 mmol) in MeOH (10 mL) was
added a 25% solution of NaOMe in MeOH to adjust the solution
to pH >12, and the mixture was stirred at room temperature for
3 h, when TLC (CHCl3–MeOH, 10 : 1, v/v) indicated that the
reaction was complete. The reaction mixture was neutralized with
Amberlite IR-120 (H+ form), filtered, and concentrated to give
the 2,4,6-triol. To a dry pyridine (10 mL) solution of the resulting
triol, DMAP (165 mg, 1.35 mmol), and chlorotriphenylmethane
(362 mg, 1.3 mmol) were added, and the solution was stirred
at 60 ◦C for 5 h, when TLC (toluene–EtOAc, 20 : 1, v/v)
indicated that the reaction was completed. After addition of
benzoyl chloride (0.6 mL, 5.6 mmol), the reaction mixture was
stirred at 60 ◦C, overnight. The mixture was partitioned between
CHCl3 and ice-water. The organic phase was washed with 1 M
HCl, sat. aq. NaHCO3, brine, dried (MgSO4), and concentrated.
Purification on silica gel column chromatography with hexane–
EtOAc, 20 : 1→5 : 1, v/v as the eluant afforded compound 19
(700 mg, 91%). [a]2D6 = −19.8 (c 1.22, CHCl3); 1H NMR (300 MHz,
CDCl3): d 8.20–7.10 (m, 25H, CHarom), 5.62 (ddd, 1H, J = 5.8 Hz,
˚
ular sieves used for glycosylation were MS4A, which were activated
at 200 ◦C under reduced pressure prior to use. Reaction monitoring
was done with analytical thin-layer chromatography (TLC) on
silica gel 60F254 plates (layer-thickness, 0.25 mm; E. Merck,
Darmstadt, Germany), which were visualized under UV (254 nm)
and/or by spraying with p-methoxybenzaldehyde–H2SO4–MeOH
(1 : 2 : 17, v/v). Medium pressure column chromatography was
performed on silica gel (LiChroprep Si 60; 40–63 lm, Merck,
Darmstadt, Germany). Column chromatography was performed
on silica gel (Silica gel 60;70–230meshASTM, Merck, Darmstadt,
Germany).
1H and 13C NMR spectra were recorded with a Bruker ASX
300 (300 and 75.1 MHz, respectively), JEOL A 500 (500 and
125 MHz) or JEOL ECA 600 (600 and 150 MHz). Splitting
patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet;
1
m, multiplet; brs, broad singlet for H NMR data. Signals were
assigned on the basis of 1H-1H COSY and 1H-1H TOCSY NMR
experiments. ESI-HR mass spectra were recorded on a JEOL
JMS-100TJ spectrometer and ESI-TOF HR mass spectra were
measured on a Bruker micro TOF focus spectrometer. MALDI-
TOF mass spectrometry was carried out using a Bruker-Daltonik
Ultraflex TOF mass spectrometer equipped with a pulsed ion
extraction system.
=
J = 8.0 Hz, J = 16.9 Hz, CH2–CH CH2), 5.52 (t, 1H, J2, 3
=
9.6 Hz, H-2), 5.51 (t, 1H, J4, 5 = 9.6 Hz, H-4), 5.05 (dd, 1H, J =
=
1.4 Hz, J = 17.2 Hz, CH2–CH CH2), 4.93 (d, 1H, J = 10.4 Hz,
=
CH2–CH CH2), 4.77 (d, 1H, J1, 2 = 10.0 Hz, H-1), 4.09 (d, 2H,
=
CH2–CH CH2), 4.00 (t, 1H, J3, 4 = 9.2 Hz, H-3), 3.84–3.81 (m,
1H, H-5), 3.50–3.30 (m, 2H, H-6a, 6b), 3.04–2.80 (m, 2H, SCH2),
1.85–1.68, 1.47–1.28 (m, 20H, SCH2(CH2)10CH3), 0.98 (t, 3H, J =
6.9 Hz, CH2CH3); 13C NMR (75 MHz, CDCl3): d 171.3, 165.2,
164.9, 147.1, 143.9, 143.5, 134.5, 133.4, 133.3, 130.0, 129.9, 129.2,
128.8, 128.7, 128.5, 128.2, 128.1, 127.9, 127.4, 127.3, 127.1, 117.6,
86.8, 83.9, 81.6, 78.5, 73.5, 72.6, 71.0, 63.0, 60.6, 32.1, 30.2, 30.1,
29.9, 29.8, 29.6, 29.3, 29.3, 22.9, 14.4; ESI-HRMS (m/z) calcd for
C54H62O7SNa+: 877.4108; Found: 877.4113.
Dodecyl 2,4,6-tri-O-acetyl-3-allyl-O-1-thio-b-D-glucopyranoside
(18)
Compound 176 (500 mg, 1.3 mmol) and 1-dodecanethiol (0.5 mL,
2.0 mmol) was dissolved in 1,2-dichloroethane (10 mL) and the
solution was cooled to 0 ◦C. To the solution was added slowly
BF3·Et2O (0.45 mL, 1.9 mmol), then the mixture was stirred for
30 min at 0 ◦C. TLC (toluene–EtOAc, 5 : 1, v/v) confirmed
complete disappearance of the stating material. The reaction
mixture was poured into ice-water, and extracted with CHCl3. The
resulting mixture was successively washed with saturated aqueous
(sat. aq.) NaHCO3, brine, dried (MgSO4), and concentrated. The
residue was recrystallized in EtOH to yield 18 (600 mg, 87%).
Dodecyl 3-O-allyl-2,4-di-O-benzoyl-6-O-chloroacetyl-1-thio-b-
D-glucopyranoside (3)
To a solution of the tritylated compound 19 (500 mg, 0.58 mmol)
in acetic acid (40 mL) was added H2O (8 mL) at 70 ◦C. The
mixture was stirred at this temperature for 1 h, after which time
the reaction was completed as indicated by TLC (hexane–EtOAc,
3 : 1, v/v). The reaction mixture was evaporated, then subjected to
co-evaporation with toluene three times. Purification on silica gel
column chromatography (hexane–EtOAc, 7 : 1→5 : 1, v/v) gave a
colorless oil (330 mg, 93%).
A solution of the resulting de-O-tritylated thioglycoside
(330 mg, 0.54 mmol) in pyridine–CH2Cl2 (1 : 10, v/v, 10 mL)
was treated with chloroacetic anhydride (103 mg, 0.6 mmol);
the reaction was allowed to process for 3 h. The mixture was
successively washed with ice-water, sat. aq. NaHCO3, and brine,
dried (MgSO4), and concentrated. Purification with silica gel
column chromatography (hexane–EtOAc, 7 : 1→5 : 1, v/v) gave
1
[a]2D7 = −30.8 (c 1.24, CHCl3); H NMR (300 MHz, CDCl3): d
5.81 (ddd, 1H, J = 5.5 Hz, J = 10.6 Hz, J = 22.6 Hz, CH2–
=
=
CH CH2), 5.30 (d, 1H, J = 17.0 Hz, CH2–CH CH2), 5.18 (d,
=
1H, J = 7.7 Hz, CH2–CH CH2), 5.10 (t, 1H, J4, 5 = 10.2 Hz, H-4),
5.04 (t, 1H, J2, 3 = 9.8 Hz, H-2), 4.40 (d, 1H, J1, 2 = 10.0 Hz, H-1),
4.26 (dd, 1H, J5, 6b = 4.1 Hz, H-6b), 4.13 (dd, 1H, J5, 6a = 2.2 Hz,
=
J6a, 6b = 14.7 Hz, H-6a), 4.30–4.00 (m, 2H, CH2–CH CH2), 3.61
(t, 1H, J3, 4 = 9.2 Hz, H-3), 3.70–3.50 (m, 1H, H-5), 2.90–2.60 (m,
2H, SCH2), 2.10, 2.10, 2.09 (3 s, each 3H, CH3Ac), 1.87–1.65 (m,
20H, SCH2(CH2)10CH3), 0.92 (t, 3H, J = 4.1 Hz, CH2CH3); 13C
=
NMR (75 MHz, CDCl3): d 171.0, 169.5, 169.4 (C O Ac), 134.4,
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compound 5 (380 mg, 92% in two steps). [a]2D5 = −13.7 (c 0.96,
CHCl3); 1H NMR (300 MHz, CDCl3): d 8.18–7.27 (m, 10H,
CHarom), 5.54 (ddd, 1H, J = 5.8 Hz, J = 10.4 Hz, J = 22.6 Hz,
J3, 4 = 9.5 Hz, H-3), 5.68 (t, 1H, J4, 5 = 9.8 Hz, H-4), 5.64 (t, 1H,
J2, 3 = 9.5 Hz, H-2), 4.85 (d, 1H, J1, 2 = 9.8 Hz, H-1), 3.95–3.89
(m, 1H, H-5), 3.40 (dd, 1H, J5, 6a = 2.2 Hz, J6a, 6b = 10.6 Hz, H-6a),
3.30 (dd, 1H, J5, 6b = 4.9 Hz, H-6b), 2.97–2.82 (m, 2H, SCH2),
1.87–1.25 (m, 20H, SCH2(CH2)10CH3), 0.92 (t, 3H, J = 7.0 Hz,
CH2CH3); 13C NMR (75 MHz, CDCl3): d 166.2, 165.6, 165.1,
143.9, 133.5, 133.4, 133.4, 130.5, 130.2, 130.1, 130.0, 129.6, 129.3,
128.9, 128.8, 128.7, 128.6, 128.5, 128.0, 127.2, 87.0, 84.0, 74.8,
71.2, 69.7, 62.9, 60.7, 32.2, 30.3, 30.2, 30.0, 29.8, 29.7, 29.5, 29.3,
23.0, 14.5; ESI-HRMS (m/z) calcd for C58H62O8SNa+: 941.4058;
Found: 941.4061.
=
CH2–CH CH2), 5.39 (t, 1H, J4, 5 = 9.7 Hz, H-4), 5.35 (t, 1H,
J2, 3 = 9.7 Hz, H-2), 5.03 (dd, 1H, J = 1.4 Hz, J = 17.2 Hz, CH2–
=
=
CH CH2), 4.90 (d, 1H, J = 10.3 Hz, CH2–CH CH2), 4.66 (d, 1H,
J1, 2 = 10.0 Hz, H-1), 4.38–4.31 (m, 2H, H-6a, 6b), 4.10–4.00 (m,
=
4H, COCH2Cl, CH2–CH CH2), 3.98 (t, 1H, J3, 4 = 9.1 Hz, H-3),
3.95–3.78 (m, 1H, H-5), 2.78–2.63 (m, 2H, SCH2), 1.30–1.08 (m,
20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J = 7.0 Hz, CH2CH3); 13C
NMR (75 MHz, CDCl3): d 167.4, 165.4, 165.3, 140.0, 133.7, 134.4,
130.2, 130.1, 130.0, 129.4, 129.0, 128.8, 117.9, 84.3, 81.1, 73.8,
72.3, 70.8, 64.7, 63.3, 41.1, 30.3, 30.5, 30.0, 29.9, 29.8, 29.7, 29.5,
29.1, 23.0, 14.5; ESI-HRMS (m/z) calcd for C37H49ClO8SNa+:
711.2729; Found: 711.2748.
Dodecyl 2,3,4-tri-O-benzoyl-6-O-chloroacetyl-1-thio-b-
D-glucopyranoside (4)
To a solution of the tritylated compound 21 (500 mg, 0.5 mmol)
in acetic acid (40 mL) was added H2O (8 mL) at 70 ◦C. The
mixture was stirred at the same temperature for 1 h, when the
reaction was complete as indicated by TLC (hexane–EtOAc, 3 :
1, v/v). The reaction mixture was evaporated, then subjected to
co-evaporation with toluene three times and purification by silica
gel column chromatography (hexane–EtOAc, 7 : 1→5 : 1, v/v)
gave a colorless oil (318 mg, 94%).
A solution of the resulting de-O-tritylated thioglycoside
(318 mg, 0.47 mmol) in pyridine–CH2Cl2 (1 : 10, v/v, 10 mL) was
treated with chloroacetic anhydride (100 mg, 0.6 mmol), and the
reaction was stirred for 2 h. The mixture was successively washed
with ice water, sat. aq. NaHCO3, and brine, dried (MgSO4), and
concentrated. Purification by silica gel column chromatography
(hexane–EtOAc, 7 : 1→5 : 1, v/v) gave compound 4 (312 mg, 87%
in two steps). [a]2D5 = −6.2 (c 1.24, CHCl3); 1H NMR (300 MHz,
CDCl3): d 8.09–7.10 (m, 15H, CHarom), 5.93 (t, 1H, J3, 4 = 9.5 Hz,
H-3), 5.59 (t, 1H, J4, 5 = 10.0 Hz, H-4), 5.64 (t, 1H, J2, 3 = 9.8 Hz,
H-2), 4.83 (d, 1H, J1, 2 = 10.0 Hz, H-1), 4.50–4.30 (m, 2H, H-6a,
6b), 4.20–4.00 (m, 3H, H-5, COCH2Cl), 2.81–2.70 (m, 2H, SCH2),
1.34–1.24 (m, 20H, SCH2(CH2)10CH3), 0.92 (t, 3H, J = 6.9 Hz,
CH2CH3); 13C NMR (75 MHz, CDCl3): d 167.3, 165.5, 165.1,
165.3, 133.9, 133.6, 130.1, 130.1, 129.9, 129.3, 128.9, 128.8, 128.7,
128.6, 128.6, 84.3, 74.2, 70.7, 69.4, 64.3, 40.9, 32.2, 30.4, 29.9,
29.8, 29.8, 29.6, 29.4, 29.0, 22.9, 14.4; ESI-HRMS (m/z) calcd for
C41H49ClO9SNa+: 775.2678; Found: 775.2683.
Dodecyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (20)
To a solution of 1,2,3,4,6-penta-O-acetyl-b-D-glucopyranose
(780 mg, 2.0 mmol) and 1-dodecanethiol (0.53 mL, 2.2 mmol)
in 1,2-dichloroethane (10 mL) was added BF3·Et2O (0.3 mL,
2.4 mmol) and the solution was stirred for 40 min at room tem-
perature. The reaction was quenched with Et3N and evaporated.
The residue was recrystallized in EtOH to yield 20 (1.0 g, 94%).
1
[a]2D5 = −29.2 (c 0.12, CHCl3); H NMR (300 MHz, CDCl3): d
5.24 (t, 1H, J3, 4 = 9.3 Hz, H-3), 5.10 (t, 1H, J4, 5 = 9.5 Hz, H-4),
5.05 (t, 1H, J2, 3 = 9.4 Hz, H-2), 4.49 (d, 1H, J1, 2 = 10.0 Hz, H-1),
4.26 (dd, 1H, J5, 6b = 4.9 Hz, H-6b), 4.05 (dd, 1H, J5, 6a = 2.2 Hz,
J6a, 6b = 12.3 Hz, H-6a), 3.75–3.65 (m, 1H, H-5), 2.76–2.60 (m, 2H,
SCH2), 2.10, 2.08, 2.04, 2.03 (4 s, each 3H, CH3Ac), 1.66–1.26 (m,
20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J = 4.1 Hz, CH2CH3); 13C
=
NMR (75 MHz, CDCl3): d 171.1, 170.7, 169.9, 169.9 (C O), 84.2,
76.4, 74.5, 70.5, 68.9, 62.8, 32.4, 30.6, 30.2, 30.1, 30.1, 29.9, 29.7,
29.3, 23.2, 21.2, 21.1, 14.6; Anal. Calcd for C26H44O9S: C, 58.62;
H, 8.33; S, 6.02%; Found: C, 58.55; H, 8.46; S, 6.17%.
Dodecyl 2,3,4-tri-O-benzoyl-6-O-trityl-1-thio-b-D-glucopyranoside
(21)
To a solution of 20 (1.0 g, 1.9 mmol) in MeOH (50 mL) was added
a 25% solution of NaOMe in MeOH to adjust the pH to >12
at room temperature. After 3 h, TLC (CHCl3–MeOH, 5 : 1, v/v)
showed that the reaction was completed. The reaction mixture
was neutralized with Amberlite IR-120 (H+ form), filtered, and
concentrated in vacuo. The product and chlorotriphenylmethane
(1.2 g, 4.0 mmol) were dissolved in dry pyridine (10 mL) and the
solution was heated to 60 ◦C, overnight. TLC (toluene–EtOAc, 20 :
1, v/v) indicated that the reaction was completed, and that one
product was formed. To the reaction mixture was added benzoyl
Dodecyl 2,3,4,6-tetra-O-benzoyl-1-thio-b-D-glucopyranoside (5)
To a solution of the acetate 20 (600 mg, 1.13 mmol) in MeOH
(20 mL) was added NaOMe (20 mg), and the solution was stirred
at room temperature for 5 h. After neutralization with Amberlite
IR-120 (H+ form), the solvent was evaporated and the residue
was dissolved in pyridine (8 mL). Benzoyl chloride (0.8 mL,
6.8 mmol) was added to the solution. The mixture was stirred
at room temperature overnight, poured into crushed ice-water
and extracted with CHCl3. The extract was washed successively
with 1 M HCl, sat. aq. NaHCO3 and brine, dried with MgSO4,
and evaporated. The residue was chromatographed on silica gel
(toluene–EtOAc 20 : 1→10 : 1, v/v) to give the benzoate 5 (757 mg,
◦
chloride (1.3 mL, 11.1 mmol) at 0 C, the reaction mixture was
stirred at the same temperature for 30 min and at room temperature
overnight. TLC (hexane–EtOAc, 5 : 1, v/v) then showed that the
reaction was completed. The mixture was diluted with CHCl3, then
poured into ice-water. The organic phase was washed with 1 M
HCl, sat. aq. NaHCO3, brine, dried (MgSO4), and concentrated.
Purification on silica gel column chromatography (hexane–EtOAc,
15 : 1→5 : 1, v/v) as the eluant afforded compound 21 (1.5 g,
1
86%) as a colorless oil. [a]2D5 = +12.4 (c 1.70, CHCl3); H NMR
(300 MHz, CDCl3): d 8.03–7.17 (m, 20H, CHarom), 5.95 (t, 1H,
J3, 4 = 9.5 Hz, H-3), 5.69 (t, 1H, J4, 5 = 9.7 Hz, H-4), 5.56 (t, 1H,
J2, 3 = 9.6 Hz, H-2), 4.87 (d, 1H, J1, 2 = 10.0 Hz, H-1), 4.65 (dd,
1
86%) as a colorless oil. [a]2D6 = +0.26 (c 0.99, CHCl3); H NMR
(300 MHz, CDCl3): d 8.29–7.07 (m, 30H, CHarom), 5.86 (t, 1H,
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 1441–1449 | 1445
©

View Article Online
1H, J5, 6b = 3.1 Hz, H-6b), 4.51 (dd, 1H, J5, 6a = 5.4 Hz, J6a, 6b
=
Methyl 6-O-(6-O-2,3,4-tri-O-benzoyl-b-D-glucopyranosyl)-3-O-
allyl-2,4-di-O-benzoyl-b-D-glucopyranosyl)-2,3,4-tri-O-benzoyl-
a-D-glucopyranoside (8)
12.2 Hz, H-6a), 4.26–4.16 (m, 1H, H-5), 2.76–2.60 (m, 2H, SCH2),
1.66–1.26 (m, 20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J = 4.1 Hz,
CH2CH3); 13C NMR (75 MHz, CDCl3): d 166.4, 166.2, 165.6,
165.5, 133.8, 133.6, 133.6, 133.4, 130.2, 130.2, 130.1, 129.6, 129.2,
129.2, 128.7, 128.7, 128.6, 84.4, 76.7, 74.6, 71.1, 70.1, 63.7, 32.3,
30.5, 30.1, 30.0, 30.0, 29.9, 29.8, 29.7, 29.4, 29.1, 23.0, 14.4; Anal.
Calcd for C46H52O9S: C, 70.74; H, 6.71; S, 4.11%; Found: C, 70.92;
H, 6.65; S, 3.97%.
The glycosyl donor 4 (459 mg, 0.5 mmol) was condensed with
glycosyl acceptor 7 (452 mg, 0.42 mmol) using NIS (270 mg,
1.2 mmol), and TfOH (0.02 mmol, 5 lL) in dry CH2Cl2 (10 mL)
according to the general procedure described above. Compound 8
was obtained as colorless oil (643 mg, 92% in two steps). [a]D26
=
+0.18 (c 0.95, CHCl3); 1H NMR (600 MHz, CDCl3): d 8.10–7.10
(m, 40H, CHarom), 6.06 (t, 1H, J3, 4 = 9.7 Hz, H-3), 5.93 (t, 1H,
J3
= 9.7 Hz, H-3ꢀꢀ), 5.57–5.49 (ddd, 1H, J = 4.4 Hz, J =
ꢀꢀ ꢀꢀ
General procedure for the preparation of gentio-oligosaccharides
using NIS–TfOH
, 4
=
5.5 Hz, J = 16.4 Hz, CH2–CH CH2), 5.41 (t, 1H, J4, 5 = 9.7 Hz,
H-4), 5.27 (t, 1H, J2 , 3 = 9.8 Hz, H-2ꢀ), 5.26 (t, 1H, J4 , 5 = 9.1 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
A solution of the glycosyl donor (1.2 equiv. to acceptor), glycosyl
acceptor (1.0 equiv.) and freshly recrystallized NIS (1.2 equiv. to
donor) in CH2Cl2 was stirred for 30 min over activated molecular
sieves under a nitrogen atmosphere. TfOH (5 lL) was added at
−20 ◦C with a micro syringe. The reaction mixture was stirred
and the temperature was warmed slowly to room temperature.
After TLC (toluene–EtOAc, 5 : 1, v/v) analysis to check that the
glycosyl donor was consumed, the reaction was quenched with
Et3N (about 2 mL) and then diluted with CHCl3. The mixture
was filtered thought a Celite pad, and the filtrate was washed
successively with sat. aq. Na2S2O3, sat. aq. NaHCO3, and brine,
dried (MgSO4), and concentrated to gave a crude oil, which mainly
consisted of a chloroacetated product.
The crude mixture of the above mentioned glycosylation was
dissolved in pyridine (20 mL) and H2O (4 mL). After stirring
overnight at 50 ◦C, the reaction was completed as indication
by TLC (toluene–EtOAc, 2.5 : 1, v/v). The reaction mixture
was evaporated, then subjected to co-evaporation with toluene
three times. Purification was carried out by silica gel column
chromatography (toluene–EtOAc).
H-4ꢀ), 5.23 (t, 1H, J4
= 9.8 Hz, H-4ꢀꢀ), 5.19 (t, 1H, J2
=
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
, 3
, 5
9.3 Hz, H-2ꢀꢀ), 5.11 (dd, 1H, J = 3.8 Hz, J2, 3 = 10.2 Hz, H-2), 5.02
(d, 1H, J1, 2 = 3.8 Hz, H-1), 4.98 (dd, 1H, J = 1.6 Hz, J = 17.3 Hz,
CH2–CH CH2), 4.93 (d, 1H, J1 , 2 = 7.7 Hz, H-1ꢀ), 4.87 (dd, 1H,
=
ꢀ
ꢀ
=
ꢀꢀ ꢀꢀ
J = 1.6 Hz, J = 13.2 Hz, CH2–CH CH2), 4.59 (d, 1H, J1
=
, 2
8.2 Hz, H-1ꢀꢀ), 4.07–4.02 (m, 1H, H-5), 4.15–3.93 (m, 4H, H-6b,
6 b, CH2–CH CH2), 3.85 (t, 1H, J3 , 4 = 9.3 Hz, H-3ꢀ), 3.84–3.72
(m, 4H, H-5ꢀ, 5ꢀꢀ, 6ꢀa, 6ꢀꢀb), 3.63–3.57 (m, 1H, H-6ꢀꢀa), 3.52 (dd,
1H, J5, 6a = 6.0 Hz, J6a, 6b = 11.5 Hz, H-6a), 3.13 (s, 3H, OMe),
2.93–2.87 (m, 1H, OH); 13C NMR (75 MHz, CDCl3): d 166.1,
166.0, 165.7, 165.4, 165.2, 134.5, 133.8, 133.7, 133.6, 133.6, 133.6,
133.5, 133.4, 133.3, 130.2, 130.0, 130.0, 130.0, 130.0, 130.0, 129.4,
129.4, 129.3, 129.2, 129.0, 125.6, 117.7, 101.7, 100.9, 96.8, 79.6,
74.8, 74.0, 73.5, 73.3, 73.1, 72.4, 72.2, 72.0, 70.6, 70.1, 69.5, 68.9,
68.4, 61.5, 55.5, 21.8; ESI-HRMS (m/z) calcd for C78H70O24Na+:
1413.4149; Found: 1413.4143.
ꢀ
=
ꢀ
ꢀ
Methyl 6-O-(6-O-(6-O-(3-O-allyl-2,4-di-O-benzoyl-b-D-
glucopyranosyl)-2,3,4-tri-O-benzoyl-b-D-glucopyranosyl)-3-O-
allyl-2,4-di-O-benzoyl-b-D-glucopyranosyl)-2,3,4-tri-O-benzoyl-
a-D-glucopyranoside (11)
Methyl 6-O-(3-O-allyl-2,4-di-O-benzoyl-b-D-glucopyranosyl)-
2,3,4-tri-O-benzoyl-a-D-glucopyranoside (7)
The glycosyl donor 3 (83 mg, 0.12 mmol) was condensed with
glycosyl acceptor 8 (143 mg, 0.1 mmol) using NIS (32.4 mg,
0.144 mmol), and TfOH (0.02 mmol, 5 lL) in dry CH2Cl2 (10 mL)
according to the general procedure described above. Compound
11 was obtained as a colorless oil (198 mg, 92%). [a]2D3 = −7.6 (c
1.00, CHCl3); 1H NMR (600 MHz, CDCl3): d 8.20–7.13 (m, 50H),
ꢀꢀ ꢀꢀ
The glycosyl donor 3 (689 mg, 1.0 mmol) was condensed with
glycosyl acceptor 2 (761 mg, 1.2 mmol) using NIS (270 mg,
1.2 mmol), and TfOH (0.02 mmol, 5 lL) in dry CH2Cl2 (20 mL)
according to the general procedure described above. Compound 7
was obtained as a colorless oil (845 mg, 92% in two steps). [a]D26
=
1
+2.4 (c 1.25, CHCl3); H NMR (600 MHz, CDCl3): d 8.13–7.22
(m, 25H, CHarom), 6.07 (t, 1H, J3, 4 = 9.9 Hz, H-3), 5.60–5.50 (ddd,
6.07 (t, 1H, J3, 4 = 9.9 Hz, H-3), 5.73 (t, 1H, J3
= 9.9 Hz, H-3ꢀꢀ),
, 4
=
5.61–5.51 (m, 2H, CH2–CH CH2), 5.38 (t, 1H, J4, 5 = 9.9 Hz,
=
ꢀ
ꢀ
ꢀ
ꢀ
1H, J = 6.0 Hz, J = 11.0 Hz, J = 22.5 Hz, CH2–CH CH2),
H-4), 5.29 (t, 1H, J2 , 3 = 8.8 Hz, H-2ꢀ), 5.21 (t, 1H, J4 , 5 = 9.9 Hz,
ꢀꢀꢀ
ꢀ
ꢀ
ꢀꢀꢀ ꢀꢀꢀ
ꢀꢀ
5.42 (t, 1H, J4, 5 = 9.3 Hz, H-4), 5.30 (t, 1H, J2 , 3 = 8.2 Hz, H-
H-4ꢀ), 5.17 (t, 1H, J2
ꢀꢀ ꢀꢀ
J2
, 3
= 8.9 Hz, H-2 ), 5.11 (dd, 1H, J = 7.8 Hz,
, 3
2ꢀ), 5.19 (t, 1H, J4 , 5 = 9.3 Hz, H-4ꢀ), 5.11 (dd, 1H, J = 3.8 Hz,
= 9.8 Hz, H-2 ), 5.10 (dd, 1H, J = 3.8 Hz, J2, 3 = 10.2 Hz, H-
ꢀ
ꢀ
=
=
ꢀꢀ ꢀꢀ
J2, 3 = 10.2 Hz, H-2), 5.01 (d, 1H, J = 10.4 Hz, CH2–CH CH2),
2), 5.03 (d, 2H, J = 17.0 Hz, CH2–CH CH2), 5.00 (t, 1H, J4
=
, 5
ꢀꢀꢀ ꢀꢀꢀ
4.95 (d, 1H, J1, 2 = 3.8 Hz, H-1), 4.90 (d, 1H, J = 10.4 Hz, CH2–
9.9 Hz, H-4ꢀꢀ), 5.00 (t, 1H, J4
= 9.9 Hz, H-4ꢀꢀꢀ), 4.99 (d, 1H,
, 5
CH CH2), 4.79 (d, 1H, J1 , 2 = 8.2 Hz, H-1ꢀ), 4.23- 4.17 (m, 1H,
J1, 2 = 3.8 Hz, H-1), 4.91 (d, 2H, J = 15.9 Hz, CH2–CH CH2),
=
=
ꢀ
ꢀ
ꢀꢀꢀ ꢀꢀꢀ
ꢀꢀ ꢀꢀ
, 2
H-5), 4.09 (dd, 1H, J5, 6b = 2.2 Hz, H-6b), 4.03 (d, 2H, J = 5.5 Hz,
4.90 (d, 1H, J1
= 8.2 Hz, H-1ꢀꢀꢀ), 4.60 (d, 1H, J1
= 8.2 Hz,
, 2
CH2–CH CH2), 3.98 (t, 1H, J3 , 4 = 9.3 Hz, H-3ꢀ), 3.75 (dd, 1H,
J5, 6a = 6.6 Hz, J6a, 6b = 11.0 Hz, H-6a), 3.73–3.67 (m, 1H, H-6ꢀb),
3.65–3.60 (1 m, 1H, H-5ꢀ), 3.58–3.52 (m, 1H, H-6ꢀb), 3.15 (s, 3H,
OMe), 2.80–2.72 (m, 1H, OH); 13C NMR (75 MHz, CDCl3): d
169.7, 166.1, 166.0, 134.6, 134.0, 133.7, 133.4, 130.3, 130.2, 130.1,
130.0, 129.6, 129.4, 129.2, 128.9, 128.8, 128.6, 117.5, 101.0, 97.2,
80.0, 75.3, 73.4, 72.4, 70.9, 69.9, 68.7, 67.2, 61.8, 55.9; ESI-HRMS
(m/z) calcd for C51H48O16Na+: 939.2835; Found: 939.2833.
H-1ꢀꢀ), 4.57 (d, 1H, J1 , 2 = 8.2 Hz, H-1ꢀ), 4.12–3.95 (m, 6H, H-
=
ꢀ
ꢀ
ꢀ
ꢀ
=
ꢀꢀꢀ ꢀꢀꢀ
5, 6b, CH2–CH CH2), 3.89 (t, 1H, J3
= 9.9 Hz, H-3ꢀꢀꢀ), 3.88
, 4
(t, 1H, J3 , 4 = 9.9 Hz, H-3ꢀ), 3.86–3.81 (m 3H, H-6ꢀb, 5ꢀꢀ, 6ꢀꢀꢀa),
ꢀ
ꢀ
3.79–3.69 (m, 3H, H-6ꢀꢀa, 5ꢀꢀꢀ, 6ꢀꢀꢀb), 3.66–3.61 (m, 1H, H-5ꢀ), 3.59
(dd, 1H, J5
= 4.9 Hz, H-6ꢀꢀb), 3.53 (dd, 1H, J5 , 6 a = 1.6 Hz,
ꢀꢀ ꢀꢀ
ꢀ
ꢀ
,6
b
J6 a, 6 b = 7.2 Hz, H-6ꢀa), 3.51 (dd, 1H, J5, 6a = 6.1 Hz, J6a, 6b
=
ꢀ
ꢀ
11.3 Hz, H-6a), 3.09 (s, 3H, OMe), 2.79–2.89 (brs, 1H, OH); 13
C
NMR (75 MHz, CDCl3): d 166.5, 166.3, 166.3, 166.1, 166.0, 165.9,
1446 | Org. Biomol. Chem., 2008, 6, 1441–1449
This journal is The Royal Society of Chemistry 2008
©

View Article Online
165.8, 165.6, 165.4, 134.9, 134.8, 134.1, 134.0, 134.0, 133.9, 133.8,
133.7, 133.6, 133.5, 133.4, 131.5, 130.6, 130.5, 130.3, 130.2, 130.2,
130.1, 130.0, 129.8, 129.7, 129.5, 129.4, 129.3, 129.2, 129.1, 129.0,
129.0, 128.8, 128.7, 118.0, 117.9, 102.1, 101.3, 100.9, 97.0, 80.1,
79.9, 75.0, 74.5, 74.2, 74.0, 73.8, 73.1, 73.0, 72.8, 72.6, 71.6, 70.8,
70.2, 69.3, 68.7, 68.0, 62.1, 55.6, 39.3, 30.9, 30.3, 29.5, 24.6, 23.6,
14.6, 11.5; ESI-HRMS (m/z) calcd for C101H92O31Na+: 1823.5515;
Found: 1823.5517.
diluted with CHCl3, filtered, successively washed with sat. aq.
Na2S2O3, sat. aq. NaHCO3, and brine. After drying (MgSO4)
and concentration, the residue was purified twice by column
chromatography (hexane–EtOAc 1 : 1, followed by toluene–EtOAc
10 : 1) to provide 13 as a colorless oil (100.1 mg, 41%, a : b; 1 :
1.4).
(b) BSP–Tf2O promoted glycosylation. A solution of the
glycosyl donor 5 (141 mg, 0.18 mmol), BSP (56 mg, 0.27 mmol)
˚
and MS4A (300 mg) was stirred in dry CH2Cl2 (3 mL) at room
Methyl 6-O-(6-O-(6-O-(2,4-di-O-benzoyl-b-D-glucopyranosyl)-
2,3,4-tri-O-benzoyl-b-D-glucopyranosyl)-2,4-di-O-benzoyl-b-D-
glucopyranosyl)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (6)
temperature for 30 min under a nitrogen atmosphere. The reaction
mixture was cooled to −78 ◦C, followed by addition of Tf2O
(45 lL, 0.27 mmol) and stirred at this temperature for 15 min.
Then a solution of glycosyl acceptor 10 (179 mg, 0.12 mmol) in dry
CH2Cl2 (2 mL) was added and the reaction mixture was allowed
to slowly warm to room temperature overnight (two-dimensional
TLC, hexane–EtOAc, (1 : 1, v/v) and toluene–EtOAc (5 : 1, v/v)).
Purification as described above gave 13 (107.8 mg, 44%, b only).
To a solution of compound 11 (158 mg, 0.09 mmol) in acetic acid
(3.8 mL) and H2O (0.2 mL) were added sodium acetate (74 mg,
0.9 mmol) and palladium(II) chloride (64 mg, 0.36 mmol), and the
reaction mixture was sonicated at room temperature for 2 h. The
solution was then filtered through a celite bed and the filtrate was
extracted with CHCl3. The organic layer was washed with H2O,
sat. aq. NaHCO3, and brine, dried (MgSO4), and then purification
by silica gel column chromatography (toluene–EtOAc, 5 : 1→2 :
(c) NIS–TfOH–AgOTf promoted glycosylation. A solution of
the glycosyl donor 5 (31 mg, 40 lmol), glycosyl acceptor 10
(116 mg, 80 lmol), freshly recrystallized NIS (6.3 mg, 20 lmol),
1, v/v) gave compound 6 (139 mg, 90%) as a syrup foam. [a]D25
=
and MS4A (300 mg) in dry CH2Cl2 (4 mL) was stirred at room
˚
1
−8.7 (c 1.04, CHCl3); H NMR (500 MHz, CDCl3): d 8.20–7.13
temperature for 30 min under a nitrogen atmosphere. To the
mixture was added TfOH (2 lL, 20 lmol) at −40 ◦C and the
mixture was stirred at this temperature for 30 min. Then a solution
of AgOTf (7.2 mg, 28 lmol) in Et2O (1 mL) was added and the
reaction mixture was allowed to slowly warm to room temperature
overnight (two-dimensional TLC, hexane–EtOAc, (1 : 1,v/v) and
toluene–EtOAc (5 : 1, v/v)). Purification as described above gave
13 (22.4 mg, 28%, a : b; 1 : 1.4).
ꢀꢀ ꢀꢀ
(m, 50H), 6.08 (t, 1H, J3, 4 = 9.8 Hz, H-3), 5.79 (t, 1H, J3
=
, 4
9.8 Hz, H-3ꢀꢀ), 5.45 (t, 1H, J4, 5 = 9.8 Hz, H-4), 5.23 (dd, 1H, J =
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
, 5
7.9 Hz, J2
= 9.8 Hz, H-2ꢀꢀ), 5.18 (t, 1H, J4
= 9.6 Hz, H-4ꢀꢀ),
, 3
5.14 (t, 1H, J4 , 5 = 10.4 Hz, H-4ꢀ), 5.14 (t, 1H, J2 , 3 = 9.2 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
H-2ꢀ), 5.12 (t, 1H, J2, 3 = 9.2 Hz, H-2), 5.06 (t, 1H, J2
= 8.5 Hz,
ꢀꢀꢀ ꢀꢀꢀ
, 3
H-2ꢀꢀꢀ), 5.06 (t, 1H, J4
= 8.5 Hz, H-4ꢀꢀꢀ), 5.02 (d, 1H, J1, 2
=
ꢀꢀꢀ ꢀꢀꢀ
, 5
3.7 Hz, H-1), 4.88 (d, 1H, J1
= 7.9 Hz, H-1ꢀꢀꢀ), 4.76 (d, 1H,
ꢀꢀꢀ ꢀꢀꢀ
, 2
J1
= 7.9 Hz, H-1ꢀꢀ), 4.62 (d, 1H, J1 , 2 = 7.9 Hz, H-1ꢀ), 4.17 (t,
ꢀꢀ ꢀꢀ
ꢀ
ꢀ
, 2
(d) ICl–AgOTf promoted glycosylation. A solution of the
glycosyl donor 5 (31 mg, 40 lmol), glycosyl acceptor 10 (116 mg,
1H, J3
= 9.2 Hz, H-3ꢀꢀꢀ), 4.15–4.90 (m, 1H, H-5), 4.01 (dd, 1H,
ꢀꢀꢀ ꢀꢀꢀ
, 4
J5, 6b = 1.8 Hz, H-6b), 3.96 (t, 1H, J3 , 4 = 9.2 Hz, H-3ꢀ), 3.92–3.98
ꢀ
ꢀ
˚
80 lmol), AgOTf (15 mg, 60 lmol), and MS4A (300 mg) in dry
(m, 1H, H-5ꢀꢀ), 3.93 (dd, 1H, J5 b = 3.7 Hz, H-6ꢀꢀb), 3.89 (dd, 1H,
ꢀꢀ ꢀꢀ
, 6
CH2Cl2 (4 mL) was stirred at room temperature for 30 min under a
nitrogen atmosphere. The reaction mixture was cooled to −40 ◦C,
followed by the addition of ICl (10 lL, 0.28 mmol) in CH2Cl2
(1 mL), and the temperature was increased gradually from −40 ◦C
to room temperature overnight (two-dimensional TLC, hexane–
EtOAc, (1 : 1, v/v) and toluene–EtOAc (5 : 1, v/v)) to give no
trace condensation products.
Repeated column chromatography of the anomeric mixture
of the tetraglucoside with toluene–EtOAc gave pure a- and b-
anomers. Spectroscopic data for the b-anomer was identical with
that previously prepared by the van Boom group.3
J5 , 6 b = 6.1 Hz, H-6ꢀb), 3.81 (dd, 1H, J5
= 6.1 Hz, J6
=
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
ꢀꢀ
ꢀꢀ
a, 6 b
, 6
a
11.0 Hz, H-6ꢀꢀa), 3.78 (dd, 1H, J5
b = 3.0 Hz, H-6ꢀꢀꢀb), 3.75 (dd,
ꢀꢀꢀ ꢀꢀꢀ
, 6
1H, J5 , 6 a = 1.6 Hz, J6 a, 6 b = 7.2 Hz, H-6ꢀa), 3.72–3.60 (m, 3H,
H-5ꢀ, 5ꢀꢀꢀ, 6ꢀꢀꢀa), 3.59 (dd, 1H, J5, 6a = 6.1 Hz, J6a, 6b = 11.3 Hz, H-6a),
3.16 (s, 3H, OMe), 3.00–2.88 (brs, 3H, OH); 13C NMR (75 MHz,
CDCl3): d 166.9, 166.7, 166.5, 166.4, 166.1, 166.0, 165.9, 165.8,
165.4, 133.9, 133.8, 130.7, 130.6, 130.5, 130.4, 130.3, 130.2, 130.1,
129.9, 129.7, 129.4, 129.2, 128.9, 128.8, 128.7, 128.6, 128.5, 101.4,
101.1, 101.0, 97.0, 75.1, 74.8, 73.9, 73.4, 73.0, 72.3, 70.7, 70.3,
70.1, 69.2, 68.7, 68.4, 68.3, 61.9, 55.6; ESI-HRMS (m/z) calcd for
C95H84O31Na+: 1743.5889; Found: 1743.5891.
ꢀ
ꢀ
ꢀ
ꢀ
a-Anomer. [a]2D5 = −0.54 (c 1.00, CHCl3); 1H NMR (600 MHz,
CDCl3): d 8.14–7.03 (m, 65H, CHarom), 6.08 (t, 1H, J3, 4 = 9.9 Hz,
Methyl 6-O-(3,6-di-O-(2,3,4,6-tetra-O-benzoyl-b-D-
glucopyranosyl)-2,4-di-O-benzoyl-b-D-glucopyranosyl)-2,3,4-
tri-O-benzoyl-a-D-glucopyranoside (13)
H-3), 6.03 (t, 1H, J3
= 9.9 Hz, H-3ꢀꢀ), 5.87 (t, 1H, J3
=
ꢀꢀ ꢀꢀ
ꢀꢀꢀ ꢀꢀꢀ
, 4
, 4
9.9 Hz, H-3ꢀꢀꢀ), 5.56 (t, 1H, J4
= 9.9 Hz, H-4ꢀꢀ), 5.51 (t, 1H,
ꢀꢀ ꢀꢀ
, 5
= 9.8 Hz, H-4ꢀꢀꢀ), 5.46 (d,
ꢀꢀꢀ ꢀꢀꢀ
J4, 5 = 9.9 Hz, H-4), 5.48 (t, 1H, J4
, 5
= 3.8 Hz, H-1ꢀꢀꢀ), 5.35 (t, 1H, J2 , 3 = 8.8 Hz, H-2ꢀ), 5.35
ꢀꢀꢀ ꢀꢀꢀ
1H, J1
ꢀ
ꢀ
(a) NIS–TfOH promoted glycosylation. A solution of the gly-
cosyl donor 5 (141 mg, 0.18 mmol), glycosyl acceptor 10 (170 mg,
0.12 mmol), freshly recrystallized NIS (49 mg, 0.22 mmol), and
, 2
(t, 1H, J2
= 8.8 Hz, H-2ꢀꢀ), 5.13 (dd, 1H, J = 3.9 Hz, J2, 3
=
ꢀꢀ ꢀꢀ
, 3
= 10.4 Hz, H-2ꢀꢀꢀ),
ꢀꢀꢀ ꢀꢀꢀ
10.1 Hz, H-2), 5.11 (dd, 1H, J = 2.8 Hz, J2
, 3
MS4A (300 mg) in dry CH2Cl2 (5 mL) was stirred at room
5.08 (t, 1H, J4 , 5 = 9.9 Hz, H-4ꢀ), 5.04 (d, 1H, J1, 2 = 3.3 Hz, H-1),
˚
ꢀ
ꢀ
= 7.7 Hz, H-1ꢀꢀ), 4.53 (dd, 1H, J5
= 3.3 Hz,
ꢀꢀ ꢀꢀ
5.01 (d, 1H, J1
ꢀꢀ ꢀꢀ
, 6
temperature for 30 min under a nitrogen atmosphere. To the
mixture was added TfOH (5 lL, 0.02 mmol) at −40 ◦C. The
reaction mixture was allowed to slowly warm to room temperature
overnight (two-dimensional TLC, hexane–EtOAc, (1 : 1, v/v)
and toluene–EtOAc (5 : 1, v/v)), then quenched with Et3N and
, 2
b
H-6ꢀꢀb), 4.49 (d, 1H, J1 , 2 = 7.7 Hz, H-1ꢀ), 3.37 (dd, 1H, J5
=
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
, 6
a
5.5 Hz, J6
= 12.1 Hz, H-6ꢀꢀa), 4.29 (t, 1H, J3 , 4 = 9.4 Hz, H-
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
a, 6
b
3ꢀ), 4.25–4.19 (m, 2H, H-6b, 5ꢀꢀ), 4.20–4.13 (m, 1H, H-5), 4.02 (dd,
1H, J5
= 2.8 Hz, H-6ꢀꢀꢀb), 4.01 (m, 1H, H-5ꢀꢀꢀ), 3.77 (dd, 1H,
ꢀꢀꢀ ꢀꢀꢀ
, 6
b
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Org. Biomol. Chem., 2008, 6, 1441–1449 | 1447
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J5 , 6 b = 8.2 Hz, H-6ꢀb), 3.72 (dd, 1H, J5 , 6 a = 2.4 Hz, J6 a, 6 b
9.9 Hz, H-6ꢀa), 3.67–3.61 (m, 1H, H-5ꢀ), 3.53 (dd, 1H, J5, 6a
ꢀꢀꢀ ꢀꢀꢀ
=
=
(600 MHz, CDCl3): d 8.15–7.08 (m, 110H, CHarom), 6.10 (t, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J3A , 4A = 9.9 Hz, H-3A ), 6.00 (t, 1H, J3B, 4B = 9.9 Hz, H-3B), 5.79 (t,
1H, J3C, 4C = 9.9 Hz, H-3C), 5.58 (dd, 3H, J = 9.3 Hz, J = 19.2 Hz,
H-3Aꢀꢀ, 3Aꢀꢀꢀ, 4Aꢀ), 5.44–5.24 (m, 9H, H-2Aꢀ, 2Aꢀꢀ, 2Aꢀꢀꢀ, 4Aꢀꢀ, 4Aꢀꢀꢀ,
2.8 Hz, J6a, 6b = 12.4 Hz, H-6a), 3.47 (dd, 1H, J5
= 4.9 Hz,
, 6
a
J6
= 11.3 Hz, H-6ꢀꢀꢀa), 2.15 (s, 3H, OMe); 13C NMR
ꢀꢀꢀ
ꢀꢀꢀ
b
a, 6
ꢀ
ꢀ
(150.9 MHz, CDCl3): d 207.0, 166.2, 166.1, 165.8, 165.8, 165.7,
165.6, 165.4, 165.3, 165.2, 165.2, 164.9, 164.8, 133.6, 133.6, 133.5,
133.2, 133.2, 133.2, 133.1, 133.1, 133.1, 133.0, 133.0, 133.0, 133.0,
133.0, 133.0, 129.4, 129.4, 129.3, 129.2, 129.1, 129.1, 129.0, 128.9,
128.7, 128.6, 128.6, 128.6, 128.5, 128.3, 128.2, 128.1, 101.4, 101.1,
96.7, 74.8, 72.8, 72.5, 72.2, 72.2, 72.1, 70.8, 70.3, 70.2, 69.3, 68.7,
68.6, 68.5, 68.1, 63.3, 61.7, 55.3, 31.0, 29.8; ESI-TOF HRMS (m/z)
calcd for C116H96O34Na+: 2055.5675; Found: 2055.5669.
2B, 4B, 2C, 4C), 5.18 (t, 1H, J2D , 3D = 8.8 Hz, H-2Dꢀ), 5.03 (d, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J1A , 2A = 8.2 Hz, H-1A ), 4.98 (t, 1H, J4D , 5D = 9.9 Hz, H-4D ), 4.97
ꢀꢀꢀ
ꢀꢀꢀ
(d, 1H, J1B, 2B = 3.7 Hz, H-1B), 4.95 (d, 1H, J1A
= 9.3 Hz, H-
, 3D
, 2A
ꢀꢀ
1Aꢀꢀꢀ), 4.93 (d, 1H, J1A
= 7.7 Hz, H-1A ), 4.85 (t, 1H, J2D
=
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
, 2A
ꢀꢀ
8.8 Hz, H-2Dꢀꢀ), 4.70 (t, 1H, J4D
= 8.8 Hz, H-4D ), 4.65 (d, 1H,
ꢀꢀ
ꢀꢀ
, 5D
J1C, 2C = 8.2 Hz, H-1C), 4.58 (dd, 1H, J5A , 6 A b = 2.2 Hz, H-6Aꢀb),
ꢀ
ꢀ
4.41 (dd, 1H, J5A , 6 A a = 5.5 Hz, J6 A a, 6 A b = 14.8 Hz, H-6Aꢀa), 4.35
ꢀ
ꢀ
ꢀ
ꢀ
(d, 1H, J1D , 2D = 7.7 Hz, H-1Dꢀ), 4.37–4.31 (m, 1H, H-5Aꢀ), 4.26
ꢀ
ꢀ
= 7.7 Hz, H-1Dꢀꢀ), 4.26 (t, 1H, J3D , 4D = 8.8 Hz,
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
(d, 1H, J1D
, 2D
b-Anomer. [a]2D5 = +0.78 (c 1.02, CHCl3); 1H NMR (600 MHz,
H-3Dꢀ), 4.22 (t, 1H, J3D
= 8.8 Hz, H-3Dꢀꢀ), 4.19–4.08 (m, 2H,
ꢀꢀ
ꢀꢀ
, 4D
CDCl3): d 8.04–7.09 (m, 65H, CHarom), 6.05 (t, 1H, J3, 4 = 9.9 Hz,
H-6Aꢀꢀa, 6Aꢀꢀb), 4.05–3.93 (m, 3H, H-5Aꢀꢀ, 5Aꢀꢀꢀ, 6Aꢀꢀꢀa), 3.87 (d,
H-3), 6.01 (t, 1H, J3
= 9.9 Hz, H-3ꢀꢀ), 5.60 (t, 1H, J4, 5 = 9.9 Hz,
ꢀꢀ ꢀꢀ
, 4
= 11.5 Hz, H-6Dꢀꢀb), 3.82–3.71 (m, 5H, H-5B, 5C,
ꢀꢀ
ꢀꢀ
1H, J5D
, 6D
b
H-4), 5.55 (t, 1H, J3
= 9.3 Hz, H-3ꢀꢀꢀ), 5.43 (t, 1H, J2
=
ꢀꢀꢀ ꢀꢀꢀ
ꢀꢀ ꢀꢀ
, 3
, 4
6Ba, 6Bb, 6Da), 3.70–3.52 (m, 4H, H-5Dꢀ, 5Dꢀꢀ, 6Ca, 6Dꢀꢀa), 3.44
9.8 Hz, H-2ꢀꢀ), 5.40 (t, 1H, J4
= 9.9 Hz, H-4ꢀꢀ), 5.31 (t, 1H,
ꢀꢀ ꢀꢀ
, 5
(dd, 1H, J5D , 6D b = 7.7 Hz, H-6Dꢀb), 3.25 (dd, 1H, J5C, 6Cb = 4.4 Hz,
H-6Cb), 3.17 (dd, 1H, J5B, 6Ba = 3.8 Hz, J6Ba, 6Bb = 11.3 Hz, H-6Bb),
3.06 (s, 3H, OMe); 13C NMR (75 MHz, CDCl3): d 175.6, 165.9,
165.6, 165.4, 165.3, 165.1, 165.0, 164.9, 164.7, 164.7, 163.9, 134.1,
133.4, 133.0, 132.9, 132.8, 129.7, 129.6, 129.5, 129.4, 129.3, 129.2,
129.1, 129.0, 128.9, 128.7, 128.6, 128.4, 128.2, 128.1, 128.0, 100.9,
100.8, 100.7, 100.4, 100.1, 96.3, 81.6, 73.3, 72.9, 72.8, 72.7, 72.6,
72.0, 71.8, 70.2, 69.9, 69.7, 68.4, 63.2, 55.1, 52.8, 52.7, 51.5, 31.9;
ESI-HRMS (m/z) calcd for C197H162O58Na+: 3477.9625; Found:
3477.9663.
ꢀ
ꢀ
J2
= 8.2 Hz, H-2ꢀꢀꢀ), 5.28 (t, 1H, J4
= 9.9 Hz, H-4ꢀꢀꢀ), 5.08
ꢀꢀꢀ ꢀꢀꢀ
ꢀꢀꢀ ꢀꢀꢀ
, 3
, 5
ꢀꢀ ꢀꢀ
(dd, 1H, J = 3.3 Hz, J2, 3 = 10.4 Hz, H-2), 5.05 (d, 1H, J1
=
, 2
6.6 Hz, H-1ꢀꢀ), 5.03 (t, 1H, J2 , 3 = 7.7 Hz, H-2ꢀ), 5.01 (d, 1H,
ꢀ
ꢀ
J1, 2 = 3.3 Hz, H-1), 4.94 (t, 1H, J4 , 5 = 8.8 Hz, H-4ꢀ), 4.90 (d,
ꢀ
ꢀ
1H, J1
= 7.7 Hz, H-1ꢀꢀꢀ), 4.58 (dd, 1H, J5, 6b = 2.3 Hz, H-6b),
ꢀꢀꢀ ꢀꢀꢀ
, 2
4.41 (dd, 1H, J5, 6a = 4.9 Hz, J6a, 6b = 11.8 Hz, H-6a), 4.37 (d, 1H,
J1 , 2 = 7.7 Hz, H-1ꢀ), 4.30–4.25 (m, 1H, H-5), 4.21 (t, 1H, J3 , 4
=
ꢀ
ꢀ
ꢀ
ꢀ
8.8 Hz, H-3ꢀ), 4.11 (dd, 1H, J5
= 2.1 Hz, J6
= 8.7 Hz,
ꢀꢀꢀ ꢀꢀꢀ
ꢀꢀꢀ
ꢀꢀꢀ
a, 6 b
, 6
a
H-6ꢀꢀꢀa), 4.00 (dd, 1H, J5 , 6 b = 5.5 Hz, H-6ꢀb), 3.98–3.82 (m, 4H, H-
ꢀ
ꢀ
5ꢀꢀ, 5ꢀꢀꢀ, 6ꢀꢀb, 6ꢀꢀꢀb), 3.77 (dd, 1H, J5 , 6 a = 8.2 Hz, J6 a, 6 b = 12.1 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
H-6ꢀa), 3.72–3.69 (m, 1H, H-5ꢀ), 3.35 (dd, 1H, J5
= 6.6 Hz,
ꢀꢀ ꢀꢀ
, 6
a
Methyl 6-O-(3-O-(b-D-glucopyranosyl)-6-O-(6-O-(3,6-di-O-
(b-D-glucopyranosyl)-b-D-glucopyranosyl)-b-D-glucopyranosyl)-
b-D-glucopyranosyl)-a-D-glucopyranoside (1)
J6
b = 12.6 Hz, H-6ꢀꢀa), 3.04 (s, 3H, OMe); 13C NMR (75 MHz,
ꢀꢀ
ꢀꢀ
a, 6
CDCl3): d 166.8, 166.5, 166.3, 166.2, 166.1, 165.9, 165.8, 165.7,
165.6, 164.7, 134.0, 133.8, 133.7, 133.5, 133.4, 130.5, 130.4, 130.3,
130.0, 130.0, 130.0, 129.9, 129.8, 129.7, 129.7, 129.6, 129.5, 129.4,
129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.7, 101.9, 101.4, 97.1,
75.4, 74.1, 73.5, 73.3, 72.8, 72.7, 72.5, 72.3, 70.9, 70.4, 70.2, 70.1,
69.2, 68.9, 68.6, 63.8, 55.7, 30.3; ESI-TOF HRMS (m/z) calcd for
C116H96O34Na+: 2055.5675; Found: 2055.5672.
To a solution of 14 (14 mg, 4.0 lmol) in MeOH (0.8 mL) and H2O
(0.7 mL) was added NaOMe (28 mg) at room temperature and the
mixture was stirred at room temperature for 24 h. The reaction
mixture was treated with Amberlite IR-120B ion exchange resin
(H+ form), to give the title compound 1 (3.5 mg, 74%) as a white
solid. The spectroscopic data were consistent with the previous
reports.2c,3 1H NMR (600 MHz, D2O, 300 K): d 4.64 (d, 1H, J =
3.6 Hz), 4.57 (d, 1H, J = 7.8 Hz), 4.56 (d, 1H, J = 7.8 Hz), 4.39 (d,
1H, J = 7.2 Hz), 4.38 (d, 1H, J = 7.2 Hz), 4.37 (d, 1H, J = 7.2 Hz),
4.35 (d, 1H, J = 7.8 Hz), 3.80–3.10 (m, 41H); MALDI-TOF MS
(m/z) calcd for C43H74O36Na+: 1189.4; Found: 1189.9.
Methyl 6-O-(6-O-(6-O-(3,6-di-O-(2,3,4,6-tetra-O-benzoyl-b-D-
glucopyranosyl)-2,4-di-O-benzoyl-b-D-glucopyranosyl)-2,3,4-tri-
O-benzoyl-b-D-glucopyranosyl)-3-O-(2,3,4,6-tetra-O-benzoyl-b-D-
glucopyranosyl)-2,4-O-benzoyl-b-D-glucopyranosyl)-2,3,4-tri-
O-benzoyl-a-D-glucopyranoside (14)
A solution of the glycosyl donor 5 (185 mg, 0.24 mmol), BSP
(63 mg, 0.29 mmol) and MS4A (500 mg) was stirred in dry
Acknowledgements
˚
CH2Cl2 (4 mL) at room temperature for 30 min under a nitrogen
atmosphere. The reaction mixture was cooled to −78 ◦C, and
stirred at the same temperature for 15 min after addition of
Tf2O (0.29 mmol, 49 lL). Then a solution of glycosyl acceptor
6 (109 mg, 0.06 mmol) in dry CH2Cl2 (2 mL) was added to the
We would like to thank Ms A. Meada (Center for Instrumental
Analysis, Hokkaido University) for elemental analyses.
References
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1448 | Org. Biomol. Chem., 2008, 6, 1441–1449
This journal is
The Royal Society of Chemistry 2008
©

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