Investigation of the reactivity difference between thioglycoside donors with variant aglycon parts

Article abstract of DOI:10.1139/v02-101

The reactivity of perbenzoylated thioglycosides with various thiol aglycons has been compared and quantified using competitive glycosylation experiments. Methyl 2,3,4-tri-O-benzyl-3-D-glucopyranoside was employed as acceptor and DMTST as a promoter. The r

Full text of DOI:10.1139/v02-101

889
Investigation of the reactivity difference between
thioglycoside donors with variant aglycon parts
Martina Lahmann and Stefan Oscarson
Abstract: The reactivity of perbenzoylated thioglycosides with various thiol aglycons has been compared and quanti-
fied using competitive glycosylation experiments. Methyl 2,3,4-tri-O-benzyl-ꢀ-D-glucopyranoside was employed as ac-
ceptor and DMTST as a promoter. The reactivity was found, as expected, to depend on the electron donating properties
of the aglycon. Hence, the most reactive donor, the cyclohexyl thioglycoside, was found to be about three times as re-
active as the thioethyl glycoside, which in turn was twice as reactive as the thiomethyl donor. The thiophenyl donor
was even less reactive, whereas p-halophenyl donors were inert under the glycosylation conditions used — but could
be activated using NIS–TfOH as promoter. Furthermore, it was found that galactosyl donors were three to four times
more reactive than the corresponding glucosyl derivative. These results allowed the design of an orthogonal coupling
between thioglycosides with the same protecting groups (benzoyls) but with different thiol aglycons.
Key words: thioglycosides, orthogonal glycosylations, competititive glycosylations.
Résumé : En se basant sur des expériences de glycosylations compétitives, on a comparé et quantifié la réactivité de
thioglycosides perbenzoylés avec diverses thioaglycones. On a utilisé le 2,3,4-tri-O-benzyl-ꢀ-D-glucopyranoside de
méthyle comme accepteur et le DMTST comme promoteur. On a trouvé, tel que prévu, que la réactivité dépend du
caractère électrodonneur de l’aglycone. On a donc trouvé que le donneur le plus réactif, le thioglycoside de
cyclohexyle, est trois fois plus réactif que le glycoside de thioéthyle qui est lui-même deux fois plus réactif que le
donneur thiométhyle. Le donneur thiophényle est encore moins réactif alors que les donneurs p-halophényles sont
inertes dans les conditions de glycosylation utilisées; ils peuvent toutefois être activés en utilisant le NIS–TfOH comme
promoteur. De plus, on a trouvé que les donneurs galactosyles sont de trois à quatre fois plus réactifs que le dérivé
glucosyle correspondant. Ces résultats ont permis de mettre au point un couplage orthogonal entre des thioglycosides
avec les mêmes groupes protecteurs (benzoyles), mais des thioaglycones différentes.
Mots clés : thioglycosides, glycosylations orthogonales, glycosylations compétitives.
[Traduit par la Rédaction] Lahmann and Oscarson 893
Introduction
Thioglycoside donors have, apart from being stable sub-
stances allowing most protective group manipulations but
still easily activated by chemoselective promoters (7–9), an
additional advantage — their reactivity can be manipulated
by the introduction of different thiol aglycons. A few exam-
ples of couplings using this approach have been reported
(10–12), but no general study of the reactivity differences
has been performed. Here, we describe efforts to quantify
the reactivity difference between thioglycoside donors dif-
fering only in the aglycon moiety using competitive
glycosylation studies. In addition, a sample trisaccharide
was synthesized to relate the influence of the leaving group
to other preparative conditions.
The reactivity of a glycosyl donor in a glycosylation reac-
tion is dependent on its structure and the reaction conditions.
This has enabled orthogonal glycosylations and one-pot syn-
thesis of oligosaccharides using less reactive donors as ac-
ceptors. To achieve such glycosylations, various approaches
have been used employing the reactivity diversity of, for ex-
ample, various types of glycosyl donors (1, 2) and differ-
ently protected glycosyl donors (3–5). In the latter approach,
quantification of the influence of the various protecting
schemes on the reactivity was performed using model accep-
tors and competitive glycosylation studies (4, 5). Addi-
tionally, the effect of the promoter and solvent on the
reactivity must be considered (6).
Results and discussion
As glycosyl donors, perbenzoylated thioglycosides with
methyl (13), ethyl (13), phenyl (14), halophenyl (13), tolyl
(11), benzyl (13), n-butyl (13), n-hexyl (15, 16), isopropyl
(13), t-butyl (17), and cyclohexyl (18) aglycon substituents
(Fig. 1) have been prepared and used. As a model acceptor,
methyl 2,3,4-tri-O-benzyl-ꢀ-D-glucopyranoside (15) was
chosen. Both glucosyl and galactosyl donors were tested.
Competitive glycosylations were performed using mainly the
ethyl thioglycoside (Glc-13 or Gal-13) as a reference donor
Received 10 January 2002. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 5 July 2002.
Dedicated to the memory of Professor Raymond U. Lemieux.
M. Lahmann and S. Oscarson.1 Department of Organic
Chemistry, Arrhenius Laboratory, Floor 6, Stockholm
University, S-106 91 Stockholm, Sweden.
1Corresponding author (e-mail: s.oscarson@organ.su.se).
Can. J. Chem. 80: 889–893 (2002)
DOI: 10.1139/V02-101
© 2002 NRC Canada

890
Can. J. Chem. Vol. 80, 2002
Fig. 1. Thioglycoside donors employed in the study.
Fig. 2. HPLC spectra for entry 21 before addition of promoter
and 60 min after addition (see Experimental).
OBz
O
BzO
SR
BzO
OBz
Glc-1 R = m-ClPh
2 R = m-BrPh
8 R = Bn
9 R = i-Pr
3 R = p-BrPh 10 R = t-Bu
4 R = p-ClPh 11 R = cHex
5 R = n-Bu
6 R = n-Hex
7 R = Ph
12 R = Me
13 R = Et
14 R = Tol
OBz
BzO
O
SR
BzO
OBz
Gal- 6 R = n-Hex 12 R = Me
7 R = Ph
11 R = cHex
13 R = Et
14 R = Tol
Scheme 1.
OBz
O
OBz
BzO
BzO
BzO
O
+
SR
SEt
BzO
OBz
OBz
OH
O
BnO
BnO
DMTST, CH2Cl2
BnO
15
OMe
18), but has so far not been widely used (20). The tert-butyl
glycoside disappeared fastest (entry 22), but mainly gave the
decomposition product of the donor and very little of the
disaccharide product. In contrast, the perbenzylated tert-
butyl thioglucoside donor was found to be an excellent do-
nor, as was shown also by Stauch and Boons (21) using
IDCP as the promoter.
OBz
BzO
O
O
BzO
OBz
BnO
BnO
O
BnO
Competition glycosylations between glucosyl and
galactosyl donors showed the galactosides to be more reac-
tive (Table 1, entries 5, 9, 14, 17, and 21 compared with en-
tries 2, 3, 6, 12, and 18, respectively). A good correlation
between the different derivatives was obtained, with a reac-
tivity difference of about three to four in favour of the
galactoside, which is in good agreement with a result of
Wong and co-workers (5).
The reactivity difference between thioglycosides differing
only in their thiol aglycons is most often to small to allow
efficient orthogonal couplings, especially since the removal
of a benzoyl group is activating. Often sugars of different re-
activity and protecting group patterns as well as with differ-
ent thiol aglycons are compared (11). p-NO2-Phenyl
thioglycosides have been used as inert acceptors, but to
function as donors they have to be activated by conversion
of the nitro functionality into an acetamido group, and even
then the donor capacity is limited except for neuraminic acid
donors (22–25). So far, the only report on orthogonal cou-
plings between thioglycosides varying only in the aglycon
functionality to give disaccharide donors was performed us-
ing steric effects by Boons et al. (12). Couplings between
some of the more reactive (cHex, i-Pr, Et) perbenzoylated
glycosides donors and less reactive acceptors (Ph, Tol, PhX,
OMe
and dimethyl(methylthio)sulfonium trifluoromethylsulfonate
(DMTST) (19) as a promoter (Scheme 1). The reaction mix-
tures were analyzed by HPLC (Fig. 2). Since the product is
the same in most reactions, the relative reactivity was esti-
mated by comparing the amounts of non-reacted donors. The
results are summarized in Table 1.
As expected, the reactivity is correlated to the electron
withdrawing (donating) capacity of the aglycon substituent.
Tolyl and phenyl glycosides were slow (Table 1, entries 1–4,
15, 19, and 20), and an even more pronounced difference
was observed with halosubstituted phenyl derivatives, which
were inert under the conditions used. The latter donors were,
however, easily activated by using NIS–AgOTf as the pro-
moter. Of the alkyl glycosides tested, the methyl derivative
showed a rather low reactivity (entries 6 and 7), whereas the
n-butyl and benzyl glycosides were slightly faster (entries 8
and 10). The n-hexyl glycoside was comparable to the ethyl
glycoside in reactivity (entries 11 and 12), while the
branched alkyl glycosides, isopropyl and cyclohexyl, were
the most reactive donors. As can be seen, the cyclohexyl de-
rivative is an interesting effective donor (entries 13, 16, and
© 2002 NRC Canada

Lahmann and Oscarson
891
Table 1. Relative reactivity of thioglycosyl donors.
Scheme 2.
OBz
O
OH
O
Entry
Donor
Reference donor
Rel. react.a
BzO
BzO
BzO
SEt
1
2
3
4
5
6
7
8
Gal-7 (Ph)
Glc-7 (Ph)
Gal-13 (Et)
Glc-13 (Et)
Glc-13 (Et)
Gal-13 (Et)
Glc-13 (Et)
Glc-13 (Et)
Gal-13 (Et)
Glc-13 (Et)
Glc-13 (Et)
Glc-13 (Et)
Gal-13 (Et)
Glc-13 (Et)
Gal-13 (Et)
Glc-13 (Et)
Glc-7 (Ph)
Gal-13 (Et)
Glc-13 (Et)
Glc-13 (Et)
Glc-7 (Ph)
Glc-7 (Ph)
Glc-13 (Et)
Glc-13 (Et)
<0.1
0.1
0.1
0.2
0.4
0.4
0.5
0.7
0.7
0.7
1.0
1.0
1.4
1.6
1.9
2.1
3.4
3.6
5.8
6.1
10.3
12.5b
SPhpBr
BzO
+
OBz
Glc-13
OBz
16
Glc-14 (Tol)
Gal-14 (Tol)
Gal-7 (Ph)
Glc-12 (Me)
Gal-12 (Me)
Glc-8 (Bn)
Gal-14 (Tol)
Glc-5 (n-Bu)
Gal-6 (n-Hex)
Glc-6 (n-Hex)
Glc-9 (i-Pr)
Gal-12 (Me)
Glc-14 (Tol)
Gal-11 (cHex)
Gal-6 (n-Hex)
Glc-11 (c-Hex)
Glc-12 (Me)
Glc-6 (n-Hex)
Gal-11 (cHex)
Glc-10 (t-Bu)
DMTST
70%
OBz
O
BzO
BzO
O
OBz
BzO
BzO
O
SPhpBr
9
OBz
10
11
12
13
14
15
16
17
18
19
20
21
22
17
15, NIS/AgOTf
88%
OBz
O
BzO
BzO
O
OBz
BzO
BzO
O
O
OBz
O
BnO
BnO
18
BnO
OMe
aThe reactivity factors were calculated as followed: The peak area of
the reference donor (Dref) and the test donor (Dtest) were normalized to the
Experimental
L
L
L
integral of the reference (Rꢂ) (ꢂ-anomer): D = Dref L/R ; D = Dtest
/
L
ref
ꢂ
test
n
n
Rꢂ ; D ref = Dref n /Rnꢂ; and D test = Dtestn /Rnꢂ. From these values the
L
All organic solvents were distilled before use. Organic so-
lutions were dried over MgSO4, before concentration, which
was performed under reduced pressure at <40°C (bath tem-
perature). NMR spectra were recorded at 300 MHz or
400 MHz (Varian) (1H) or at 75 MHz or 100 MHz (13C), re-
amount of unused donor was calculated, as was the yield of product
n
L
formed from that particular donor: Yref = 1 – Dref /Dtest. Resulting in the
reactivity of the test donor: Rtest = Ytest/Yref.
bDonor decomposes.
1
4-OH, or 6-OH) were carried out, but were found to be inef-
fective due to concomitant activation of the supposed accep-
tor. The combination of employing thiocyclohexyl or
thioethyl glycosides as donors and thio p-Br-phenyl deriva-
tive 16 as acceptor, however, led to efficient product forma-
tion (Scheme 2). The amount of promoter (DMTST) had to
be reduced compared with standard conditions (1.5 equiv
instead of 2–4 equiv), which not only slowed down the cou-
plings but also effectively suppressed activation of the ac-
ceptor. The p-Br-phenyl group of the obtained disaccharide
17 could then be smoothly activated in a NIS–AgOTf-
promoted coupling with model acceptor 15 to produce a
trisaccharide 18 (26) in high yield (Scheme 2).
In conclusion, a study of the reactivity of thioglycosides
with different aglycon moieties has been performed using
competitive glycosylations. The results gave a quantitative
estimation of the differences between slow-reacting donors
with electron withdrawing aglycons and fast-reacting donors
with more electron donating aglycons, as well as the reactiv-
ity difference between glucosyl and galactosyl donors. A
preparative example of a coupling between an ethyl
thioglycoside (donor) and p-bromophenyl thioglycoside (ac-
ceptor), both carrying benzoyl protecting groups, is also de-
scribed. Although other factors such as choice of solvent and
promoter must be taken into account, these results, in combi-
nation with earlier investigations regarding the influence of
protecting groups, should be of value for designing efficient
orthogonal glycosylations between thioglycosides.
spectively, in CDCl3. For the H NMR spectra, TMS was
used as internal standard (ꢁ = 0); the 13C NMR spectra were
referenced to the chloroform signal (ꢁ = 77.17). Silica gel
MERCK 60 (0.040–0.063) was used for flash chromatogra-
phy. For the competition reactions, several stock solutions
were prepared in dry CH2Cl2. The HPLC reference was dis-
solved together with the acceptor. The DMTST solution was
left for one day at 4°C to stabilize the solution. The activity
of the promoter solution was checked before (and after) each
set of competition experiments performing a standard cou-
pling experiment following the coupling procedure for com-
petition experiments but using two equivalents of the
reference donor (thioethyl glucoside) instead. All vials and
sample tubes were dried and stored in an desiccator before
use. For taking aliquots to prepare the reaction mixtures,
glass pipettes with fixed volumes (50 L, 500 L) were
used. The HPLC solvents (CH3CN–H2O (83:17), containing
0.1% TFA) were filtered (0.45 m pores) before use. The re-
action mixtures were analyzed on an analytical reversed
phase column [column: RP C-18 (Rocket, 33 mm, ID 7 mm,
beads size 3 , Alltima C18) pH 2.0–7.5] with UV detection
(215 nm). During the analysis a low stream of helium was
bubbled through the solvents. Once the coupling product
was isolated and characterized by proton and carbon NMR.
To check for the occurrence of decomposition products, the
reactions were followed by TLC (toluene–EtOAc, 3:1; sil-
ica-gel F254 (E. Merck)) with detection by UV-light and (or)
charring with 8% sulphuric acid. MALDI-TOF spectra were
© 2002 NRC Canada

892
Can. J. Chem. Vol. 80, 2002
recorded on a Bruker Biflex III with 2>,4 >,6>-trihydroxy-
acetophenone monohydrate (THAP) as the matrix.
166.1, 165.8, 165.1 (PhCO), 135.0, 133.8, 133.5, 133.4,
132.2, 130.0, 129.9, 129.8, 128.6, 128.5, 128.5, 128.4 (aro-
matic C), 123.1 (C-Br), 85.8 (C-1), 79.0, 73.9, 70.5, 69.2,
61.5. MALDI-TOF MS calcd. for C33H27BrO8S: 662.06
[M(79Br)], 664.06 [M(81Br)]; found: 685.05 [M(79Br) +
Na]+, 687.06 [M(81Br) + Na]+, 701.03 [M(79Br) + K]+,
703.02 [M(81Br) + K]+.
Typical preparation of the donors
The peracetylated sugar (2.5 mmol, 1.0 equiv) was dis-
solved in dry CH2Cl2 (2 mL per mmol sugar). Thiol (1.2–1.5
equiv) and BF3·Et2O (1.5–2 equiv) were successively added.
When the reaction was complete (TLC: toluene–EtOAc, 3:1)
the reaction mixture was quenched with Et3N (2.5 equiv),
evaporated, and redissolved in CH2Cl2, then washed with
brine, dried, and concentrated. The crude product was fil-
tered through a plug of silica gel (toluene–EtOAc, 9:1) and
after crystallization (95% ethanol or pentane–Et2O) the ꢂ-
compounds were obtained. After removal of the acetates
with NaOMe, the crude material was benzoylated in
pyridine.
4-Bromophenyl (2,3,4,6-tetra-O-benzoyl-␤-D-glucopyran-
osyl)-(1J6)-2,3,4-tri-O-benzoyl-1-thio-␤-D-glucopyran-
oside (17)
A solution of donor Glc-13 (100 mg, 156 mol) and
acceptor 16 (100 mg, 150 mol) in dry CH2Cl2 (5 mL) was
stirred with powdered molecular sieves (4 Å, 200 mg) under
argon for 1 h, then DMTST (54 mg, 209 mol dissolved in
500 L CH2Cl2) was added. The reaction, followed by TLC
(toluene–EtOAc, 6:1), was quenched after 4 h by addition of
Et3N (100 L) and the mixture was diluted with CH2Cl2
(20 mL), filtered, and concentrated. The residue was sub-
jected to silica gel column chromatography (pentane–Et2O,
1:1 followed by toluene–EtOAc, 20:1) to obtain 17 (130 mg,
Competitive glycosylation experimental procedure
A mixture of the glycoside donor (10 mol, 1.0 equiv,
1 mmol in CH2Cl2), the reference donor (10 mol, 1.0 equiv,
1 mmol in CH2Cl2), the HPLC reference compound (5 mol,
0.5 equiv, ꢀ/ꢂ 17:83, 0.5 mmol in CH2Cl2), the acceptor
(20 mol, 2.0 equiv, 2 mmol in CH2Cl2), and molecular
sieves (4 Å) was stirred at room temperature for 30 min. An
HPLC sample (5 L) was taken, centrifuged, and analyzed.
DMTST (10 mol, 1.0 equiv., 1 mmol in CH2Cl2) was added
and HPLC samples (20 L) were taken at regular intervals
(first set: 30 min, 1 h, 2 h, 4 h, 24 h; second set: 1 h, 3 h),
centrifuged, and analyzed. All couplings were carried out as
a double experiment at the same time to minimize errors.
1
105 mol, 70%) as a white solid. H NMR ꢁ: 8.0–7.7 (m,
14H), 7.5–6.9 (m, 25H), 5.9 (t, J = 9.6 Hz, 1H), 5.8 (t, J =
9.4 Hz, 1H), 5.6 (t, J = 9.9 Hz, 1H), 5.5 (dd, J = 7.7, 9.9 Hz,
1H), 5.3 (t, J = 9.6 Hz, 1H), 5.2 (t, J = 9.9 Hz, 1H), 4.9 (d,
J = 7.7 Hz, 1H, H-1>), 4.8 (d, J = 9.9 Hz, 1H, H-1), 4.6 (dd,
J = 3.3, 12.1 Hz, 1H), 4.4 (dd, J = 4.4, 12.1 Hz, 1H), 4.0 (m,
3H), 3.9 (dd, J = 7.1, 11.5 Hz, 1H). 13C NMR ꢁ: 166.1,
165.9, 165.7, 165.4, 165.2, 165.0 (PhCO), 134.8, 133.6,
133.5, 133.4, 133.3, 132.2, 130.7, 130.0, 129.9, 129.8,
129.6, 129.3, 129.2, 128.9, 128.7, 128.5, 128.4, 128.3,
125.4, 123.0 (aromatic C), 101.5 (C-1>), 85.6 (C-1), 78.2,
74.1, 73.0, 72.5, 71.9, 70.5, 69.6, 68.7, 65.0. MALDI-TOF
MS calcd. for C67H53BrO17S: 1240.22 [M(79Br)], 1242.42
[M(81Br)]; found: 1263.25 [M(79Br) + Na]+, 1265.25
[M(81Br) + Na]+, 1279.24 [M(79Br) + K]+, 1281.25 [M(81Br) +
K]+.
4-Bromophenyl 2,3,4-tri-O-benzoyl-1-thio-␤-D-glucopy-
ranoside (16)
4-Bromophenyl 1-thio-ꢂ-D-glucopyranoside (680 mg,
1.92 mmol), dissolved in pyridine (5 mL), was stirred with
TBDMSCl (350 mg, 2.3 mmol) and DMAP (cat.) at room
temperature over night (CHCl3–MeOH, 9:1). Then benzoyl
chloride (2 mL) was added and the mixture was left stirring
for additional 2 h (toluene–EtOAc, 6:1). After aqueous work-
up, the raw material was purified by silica gel flash-
chromatography (pentane–Et2O, 3:1) to yield 4-bromophenyl
2,3,4-tri-O-benzoyl-6-O-tert-butyldimethylsilyl-1-thio-ꢂ-D-glu-
copyranoside (1.34 g, 1.72 mmol, 90%). 1H NMR ꢁ: 8.3–7.1
(m, 19H), 5.9 (t, J = 9.3 Hz, 1H), 5.5 (t, J = 9.6 Hz, 1H), 5.4
(t, J = 9.9 Hz, 1H), 5.0 (d, J = 9.6 Hz, 1H, H-1), 4.0–3.8 (m,
3H), 0.9 (s, 9H, t-BuSi), 0.0 (2s, 6H, Me2Si). 13C NMR ꢁ:
165.9, 165.1, 165.1 (PhCO), 134.5, 133.8, 133.4, 132.1,
130.3, 129.9, 129.8, 128.5, 128.5, 128.3 (aromatic C), 122.8
(C-Br), 85.8 (C-1), 79.7, 74.5, 70.6, 69.1, 62.7, 25.9 (t-
BuSi), 18.4 (t-BuSi), –5.2, –5.3 (Me2Si).
To a cooled (0°C) solution of 4-bromophenyl 2,3,4-tri-O-
benzoyl-6-O-tert-butyldimethylsilyl-1-thio-ꢂ-D-glucopyranoside
(1.28 g, 1.65 mmol) in CH2Cl2 (50 mL), was slowly added
BF3·Et2O (520 L, 4.1 mmol). After 2 h, the reaction
mixture was diluted with CH2Cl2, washed consecutively
with H2O, NaHCO3, and brine, then dried and concentrated.
The crude product was purified by silica gel flash-
chromatography (toluene J toluene–EtOAc, 6:1) to yield 16
(0.94 g, 1.42 mmol, 86%). 1H NMR ꢁ: 8.0–7.8 (m, 6H), 7.6–
7.1 (m, 13H), 5.9 (t, J = 9.6 Hz, 1H), 5.4 (t, J = 9.6 Hz, 2H),
5.0 (d, J = 9.6 Hz, 1H, H-1), 3.9–3.7 (m, 3H). 13C NMR ꢁ:
Methyl (2,3,4,6-tetra-O-benzoyl-␤-D-glucopyranosyl)-
(1J6)-(2,3,4-tri-O-benzoyl-␤-D-glucopyranosyl)-(1J6)-
2,3,4-tri-O-benzyl-␣-D-glucopyranoside (18) (26)
A solution of donor 17 (40 mg, 32 mol) and acceptor 15
(18 mg, 39 mol) in dry CH2Cl2 (2 mL) was stirred with
powdered molecular sieves (4 Å, 100 mg) under argon for
1 h. The mixture was cooled (0°C) and NIS (11 mg,
49 mol) and AgOTf (cat.) were added. The reaction, fol-
lowed by TLC (toluene–EtOAc, 6:1), was quenched after
30 min by addition of Et3N (50 L), the mixture was then
diluted with CH2Cl2 (20 mL), filtered, and concentrated. The
residue was subjected to silica gel column chromatography
(toluene J toluene–EtOAc, 10:1) to yield 18 (42 mg,
1
28 mol, 88%). H NMR ꢁ: 8.0–7.7 (m, 14H), 7.5–6.9 (m,
36H), 5.8 (t, J = 10 Hz, 1H), 5.7 (t, J = 10 Hz, 1H), 5.6 (t,
J = 10 Hz, 1H), 5.4 (m~dd, J = 10 Hz, J = 8 Hz, 2H), 5.3 (t,
J = 10 Hz, 1H), 5.0 (d, J = 7.8 Hz, 1H,), 4.9 (d, J = 11 Hz),
4.7 (d, J = 12 Hz, 1H), 4.6 (d, J = 11 Hz, 1H), 4.5 (m, 3H),
4.4 (d, J = 8 Hz, 1H), 4.3 (m, 2H), 4.1 (d, J = 11 Hz, 1H),
4.0 (m, 2H), 3.8 (m, 4H), 3.5–3.3 (m, 4H), 3.3 (s, 3H) ppm.
13C NMR ꢁ: 166.1, 165.8, 165.4, 165.1, 164.9 (PhCO),
139.7–137.5, 133.5–127.4 (aromatic C), 101.5, 100.8 (C-1>,
C-1>>), 98.2 (C-1), 81.9, 79.8, 75.5, 74.5, 74.4, 73.5, 72.8,
© 2002 NRC Canada

Lahmann and Oscarson
893
9. T. Norberg. In Modern methods in carbohydrate synthesis.
Edited by S.H. Khan and R.A. O’Neill. Harwood Academic
Publishers, Amsterdam. 1995. p. 82–106.
10. H.M. Zuurmond, S.C.v.d. Laan, G.A.v.d. Marel, and J.H.v.
Boom. Carbohydr. Res. 215, c1 (1991).
72.4, 72.1, 71.8, 69.7, 69.6, 69.4, 68.6, 67.6, 63.0, 55.4
(OMe). MALDI-TOF MS calcd. for C89H80O23: 1516.51
[M]+; found: 1539.53 [M + Na]+.
11. A.K. Choudhury, I. Mukherjee, B. Mukhopadhyay, and N. Roy.
J. Carbohydr. Chem. 18, 361 (1999).
12. R. Guertsen, D.S. Holmes, and G.J. Boons. J. Org. Chem. 62,
8145 (1997).
13. M. Cerny and J. Pacak. Collection Czechoslov. Chem.
Commun. 24, 2566 (1959).
14. R.J. Ferrier and R.H. Furneaux. Carbohydr. Res. 52, 63 (1976).
15. S. Saito and T. Tsuchiya. Chem. Pharm. Bull. 33, 503 (1985).
16. S.A. Galema, J.B.F.N. Engberts, and H.A. van Doren.
Carbohydr. Res. 303, 423 (1997).
Acknowledgments
We thank Professor Per Garegg for his interest in this re-
search. Financial support from EU (Contract Number ERB
FMRX CT96 0025) and from the Swedish Natural Science
Research Council are gratefully acknowledged.
17. H.B. Wood, B. Coxon, H.W. Diehl, and H.G. Fletcher. J. Org.
Chem. 29, 461 (1964).
References
18. T. Ogawa and M. Matsui. Carbohydr. Res. 54, c17 (1977).
19. P. Fügedi and P.J. Garegg. Carbohydr. Res. 149, c9 (1986).
20. P.J. Garegg, S. Oscarson, and U. Tedebark. J. Carbohydr.
Chem. 17, 587 (1998).
21. T. Stauch and G.J. Boons Synlett, 906 (1996).
22. R. Roy, F.O. Andersson, and M. Letellier Tetrahedron Lett. 33,
6053 (1992).
1. O. Kanie, Y. Ito, and T. Ogawa. J. Am. Chem. Soc. 116, 12073
(1994).
2. S. Raghavan and D. Kahne. J. Am. Chem. Soc. 11, 1580
(1993).
3. D.R. Mootoo, P. Konradsson, U. Udodong, and B. Fraser-Reid.
J. Am. Chem. Soc. 110, 5583 (1988).
4. N.L. Douglas, S.V. Ley, U. Lucking, and S.L. Warriner. J.
Chem. Soc. Perkin Trans. 1, 51 (1998).
23. L.A.J.M. Sliedregt, K. Zegelaarjaarsveld, G.A. van den Marel,
and J.H. van Boom. Synlett, 335 (1993).
5. Z. Zhang, I.R. Ollman, X.-S. Ye, R. Wischnat, T. Baasov, and
C.-H. Wong. J. Am. Chem. Soc. 121, 734 (1999).
6. M. Lahmann and S. Oscarson. Org. Lett. 2, 3881 (2000).
7. S. Oscarson. In Oligosaccharides in chemistry and biology: A
comprehensive handbook. Vol. 1. Edited by B. Ernst, G. Hart,
and P. Sinaÿ. Wiley-VCH, Weinheim. 2000. p. 93–116.
8. P.J. Garegg. Adv. Carbohydr. Chem. Biochem. 52, 179 (1997).
24. L.A.J.M. Sliedregt, G.A. van den Marel, and J.H. van Boom.
Indian Acad. Sci. Chem. Sci. 106, 1213 (1994).
25. S. Cao, F. Hernández-Matéo, and R. Roy. J. Carbohydr. Chem.
17, 609 (1998).
26. T. Zhu and G.-J. Boons Tetrahedron Lett. 39, 2187 (1998).
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