2-Bromoethyl glycosides for synthesis of glycoconjugates on solid support

Article abstract of DOI:10.1016/j.tet.2005.01.015

2-Bromoethyl glycosides can easily and in high yields be transformed into sulfones by treatment with a suitable thiol followed by oxidation with mCPBA. The observation that the so formed sulfones were cleaved by treatment with NaOMe/MeOH was used to desig

Full text of DOI:10.1016/j.tet.2005.01.015

Tetrahedron 61 (2005) 2421–2429
2-Bromoethyl glycosides for synthesis of glycoconjugates
on solid support
*
Ulf Ellervik, Marten Jacobsson and Jorgen Ohlsson
˚
¨
Organic and Bioorganic Chemistry, Center for Chemistry and Chemical Engineering, Lund University, PO Box 124, SE-221 00 Lund, Sweden
Received 24 September 2004; revised 26 November 2004; accepted 7 January 2005
Available online 28 January 2005
Abstract—2-Bromoethyl glycosides can easily and in high yields be transformed into sulfones by treatment with a suitable thiol followed by
oxidation with mCPBA. The observation that the so formed sulfones were cleaved by treatment with NaOMe/MeOH was used to design a
new safety catch linker for synthesis of glycoconjugates on solid support.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
more advanced and automated synthesis is becoming a
realistic goal2,7 further linker systems are needed.
Especially attractive are safety-catch linkers, that is, linkers
that are stable to most conditions until activated by, for
example, oxidation or reduction.8,9
Since the introduction of solid phase peptide synthesis by
Merrifield in 1963,1 polymer-supported synthesis has
become the method of choice for synthesis of peptides
and oligonucleotides. The first investigations into solid-
phase oligosaccharide synthesis were conducted in the early
1970s and, whilst some groundbreaking work was done,
progress was halted by the lack of powerful glycosylating
agents, diverse protecting groups and on-bead analytical
techniques.2 As advances were made in the solution phase
synthesis of complex carbohydrates, new protecting groups,
and selective glycosylating agents became available during
the 1990s thus fuelling the interest in solid phase
oligosaccharide synthesis. Also, on-bead analytical tech-
niques such as high-resolution magic angle spinning NMR
and FT-IR became widely available.
2-Bromoethyl was introduced as an anomeric protecting
group that can be transformed into a spacer for glycoconju-
gates.10 The 2-bromoethyl group is easily introduced by
normal glycosylation of 2-bromoethanol and is stable
towards standard reagents used in carbohydrate synthesis.11
It shows unusual stability towards anomerization.12
The formed glycosides can then be alkylated using different
thiols by treatment with, for example, Cs2CO3 in DMF.13
Presently, complex oligosaccharides are synthesized on
solid phase using a wide variety of linker systems, glycosyl
donors and acceptors, promoter systems and strategies.2 A
number of different linker systems suitable for solid phase
oligosaccharide synthesis are available with differences in
stability, cleavage reagents and the group introduced upon
cleavage. Notable examples are silyl ether linkers,3,4 acid-
and base-labile linkers such as amino-functionalized Rink
resin5 and a benzylidene acetal-type linker to Wang
aldehyde resin.6 Also, thioglycoside linkers have been
used, as well as linkers cleaved by oxidation, hydro-
genation, photocleavage and even olefin metathesis.2 Even
though solid phase oligosaccharide synthesis is becoming
Keywords: Solid support; Glycoconjugates; Safety catch linker.
* Corresponding author. Tel.: C46 46 2228220; fax: C46 46 2228209;
e-mail: ulf.ellervik@bioorganic.lth.se
Scheme 1. Deprotection of 1 under basic conditions (0.05 M NaOMe–
MeOH) gave the desired product 2 as well as glucose (3).
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.015

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U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
These thioethers are easily oxidized to sulfones using
m-chloroperbenzoic acid (mCPBA). An attempt to deacetyl-
ate the sulfone 1 (Scheme 1) under basic conditions (0.05 M
NaOMe–MeOH) gave the desired product 2 as well as a
small amount of free glucose (3), that is, the aglycon was
cleaved off. We realized that 2-bromoethyl glycosides can
be coupled to solid supported thiols and thereby be used for
solid phase glycoside synthesis.
cleavage was likewise obtained with lower concentrations
of NaOMe, although requiring longer reaction times. As a
lower limit a 0.05 M solution was used, resulting in a
reaction time of 56 h. However, investigation of the
cleavage products showed that compound 616 (Fig. 1) was
formed instead of the expected alkene.
Performing the reaction in NaOEt–EtOH (1.0 M) similarly
gave D-glucose in quantitative yield, along with compound
716 (Fig. 1). An NMR-study was performed in order to
elucidate the reaction mechanism. The model compound 1
was thus treated with a 0.7 M NaOCD3–CD3OD-solution
and NMR-spectra were recorded over a period of 300 min.
After 1 min complete deacetylation was observed along
with about 50% exchange of the protons in a-position to the
sulfone. The exchange of a-protons was complete within
5 min. The ratio of the integral of the anomeric NMR-
signals for the formed glucose compared to the total integral
of the anomeric protons of glucose (3) and deacetylated
bromoethyl glucoside (2) was measured and is shown in
Figure 2. About 10% glucose was formed within 5 min,
whereas complete conversion required 300 min. During the
experiment no signals corresponding to alkene protons were
observed.
2. Cleavage of bromoethyl glycosides in solution
Before performing the reaction on solid support, an
investigation of the system was performed in solution. As
a model for the linker, compound 1 was chosen. The model
compound was synthesized from 2-bromoethyl tetra-O-
acetyl-b-D-glucopyranoside 414,15 in two steps (Scheme 2).
Treatment of 4 with thiophenol and Cs2CO3 gave 5 in 95%
yield. The sulfide 5 was then oxidized to the corresponding
sulfone 1 in 98% yield using mCPBA.
Scheme 2. (a) Thiophenol, Cs2CO3, DMF, 2 h. (b) mCPBA, EtOAc,
30 min. (c) NaOMe–MeOH, 4–56 h.
It was anticipated that basic treatment of compound 1 would
result in abstraction of an a-proton (a relative to the
sulfone), leading to an elimination reaction with concomi-
tant expulsion of the glucoside. Thus, treatment of 1 with
NaOMe–MeOH (1.0 M) smoothly furnished an a/b-mixture
of D-glucose in quantitative yield within 4 h. Complete
Figure 2. Formation of glucose (3) by treating the sulfone 1 with 0.7 M
NaOCD3–CD3OD. The graph shows the percentage of the integral for the
NMR-signals of the anomeric protons of glucose (3) compared to the total
integral for the anomeric protons of glucose (3) and deacetylated
bromoethyl glycoside (2).
The fact that the deuterium–hydrogen exchange of the
protons in a-position to the sulfone is much faster than
formation of glucose indicates that the reaction follows a
reversible carbanion elimination (E1cB)R, followed by a
fast addition of the nucleophile (methoxide or ethoxide).
This is supported by observations in similar systems,
PhSO2CH2CH2Z, with leaving groups (Z) other than
carbohydrates.16
Figure 1. Cleavage products formed during alkoxide treatment of 1.

U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
2423
However, to disprove an SN2-mechanism, we performed a
second experiment where a glucoside carrying a propyl
linker (compound 10) was synthesized in two steps from the
known 2-bromopropyl 2,3,4,6-tetra-O-acetyl-b-D-gluco-
pyranoside15 (8, Scheme 3), in a manner similar to that
described for compound 1. Treatment of 10 with NaOMe–
MeOH (1.0 M) gave an almost quantitative yield of
compound 11; hence no cleavage product was observed.
Scheme 4. (a) NaOMe-MeOH, 45 min. (b) DMF, NaH, BnBr, 1 h.
(c) mCPBA, EtOAc, 0.5 h. (d) NaOMe–MeOH, 22 h.
with anthraldehyde dimethyl acetal, and then acetylated
using standard conditions to give compound 16 (Scheme 5).
Scheme 3. (a) Thiophenol, Cs2CO3, DMF, 1 h. (b) mCPBA, EtOAc, 0.5 h.
(c) NaOMe–MeOH, CH2Cl2, 24 h.
As a final experiment compound 15 was synthesized from 4
in four steps, in order to verify the generality of the cleavage
reaction. Compound 4 was deacetylated and subsequently
benzylated under basic conditions to give 13. The sulfide 13
was then oxidized to the sulfone 14. Treatment of 14 with
NaOMe–MeOH (1.0 M) gave compound 15 in 74% yield
together with compound 6 (Scheme 4).
3. Use of 2-bromoethyl glycosides on solid support
Scheme 5. (i) NaOMe–MeOH–CH2Cl2, 20 min. (ii) Anthraldehyde
dimethyl acetal, MeCN, pTSA, overnight. (iii) Pyridine, Ac2O, overnight.
To evaluate the bromoethyl group as a linker for solid phase
carbohydrate synthesis we performed a series of experi-
ments in order to optimize the coupling of the glycosides to
thiol resin. Cesium carbonate was used as base in solution
phase but the poor solubility in DMF makes it less suitable
for solid phase reactions. Instead the non-nucleophilic base
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was investi-
gated and turned out to work well.
We decided to use a relatively inexpensive scavenger resin,
3-(3-mercaptophenyl)propanamidomethylpolystyrene resin,
as solid support. The resin was first treated with tributyl
phosphine (0.7 M in THF–H2O 95:5) to reduce any
disulfides and then swelled in DMF. DBU (1 equiv to
resin substitution) was then added followed by different
equivalents of compound 16. Samples were taken from the
solution at various time intervals, diluted with MeCN and
the absorbance measured at 364 nm. Treatment with
0.5 equiv (to resin substitution) of 16 resulted in an almost
complete loss of absorbance in about 10 min, indicating that
all material was coupled to the resin. Addition of 1.0 equiv
of 16 resulted in about 70% reduction of the original
To follow the reactions we used the newly developed
anthraldehyde protective group which shows a strong UV-
absorbance at around 365 nm and also a strong fluor-
escence.17 Compound 4 was deprotected using NaOMe–
MeOH, transformed into the fluorescent acetal by treatment

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U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
absorbance, which gives an indication of the practically
useful loading of the resin for this coupling (Fig. 3).
To verify that compound 16 had been coupled to the resin
the two samples, treated with 0.5 equiv of 16 and 17,
respectively, were washed with several volumes of DMF
and CH2Cl2 and then swelled in a mixture of MeOH and
CH2Cl2 and illuminated with long wave UV-radiation
(365 nm). As expected, only the resin treated with 16
showed a strong fluorescence (Fig. 4).
The stability of the thioethyl linker was investigated by
subjecting compound 5 or 12 to standard conditions used in
synthetic carbohydrate chemistry, such as basic, acidic or
reductive protective group manipulations as well as typical
glycosylation conditions (NIS–TfOH or BF3$OEt2). The
results, summarized in Table 1, show that the thioethyl
linker is stable to typical conditions. However, treatment
with BF3$OEt2 caused anomerization (16%).
Table 1. Stability of the thioethyl linker. Compound 5 or 12 was subjected
to the conditions below. The samples were purified and analyzed using
NMR
Reaction
Conditions
Product
Acylation
Deacylation
Pyridine, Ac2O, 16 h
NaOMe-MeOH (0.05 M), 1 h
HCl-MeOH, 16 h
PhCH(OMe)2, pTsOH, CH3CN, 3 h
AcOH (80%), 90 8C, 3 h
BnBr, NaH, DMF, 16 h
Pd-C (10%), AcOH, H2 (500 psi), 2 h
NIS, TfOH, MS-AW 300, CH2Cl2,
0 8C, 30 min
5
12
12
5
5
13
5
Acetal formation
Acetal cleavage
Benzylation
Debenzylation
Glycosylation
Figure 3. Coupling of 16 to thiophenyl resin using 0.5 equiv (C) and
1.0 equiv (&). As a control the resin was treated with 0.5 equiv of the
unreactive 17 (,). Samples were taken from the solution at various time
intervals and diluted with acetonitrile and the absorbance measured at
364 nm.
5
BF3OEt2, CH2Cl2, 1 h
5 (a/b 1:5)
As a control, compound 1717 with an unreactive trimethyl-
silylethyl group was subjected to the same conditions and
showed, as expected, only a minute drop in absorbance due
to dilution but no coupling.
To estimate the possible overall yield using the bromoethyl
linker we coupled compound 4 (0.5 equiv to resin
substitution) to the resin using DBU as base. Methyl iodide
was then added to cap the residual thiol groups and the resin
was washed and the sulfide oxidized to sulfone using
mCPBA. The resin was again washed and then cleaved by
treatment with 0.2 M NaOMe–MeOH–CH2Cl2 overnight to
give glucose in an excellent 55% yield after purification.
With a working protocol for using bromoethyl glycosides on
solid support we decided to illustrate the usefulness of this
novel linker with a more advanced compound. Compound
22 was synthesized in four steps from the known compound
1818 (Scheme 6). The benzylidene acetal protecting group of
compound 18 was cleaved off using 80% AcOH at 90 8C.
In a one-pot procedure the primary hydroxyl group of the
formed diol 19 was selectively benzoylated at K78 8C and
the secondary hydroxyl group was then transformed into a
trifluoromethanesulfonate and consecutively inverted using
NaN3 in DMF. The total yield for this conversion was 86%.
All attempts to glycosylate compound 20 using 2-bromo-
ethanol resulted either in de-O-acetylation of position 2
(using NIS and TMSOTf) or formation of the chloro sugar
(using ICl and AgOTf).19 Instead compound 20 was de-O-
acetylated and then O-benzoylated. The benzoylated
compound was easily glycosylated using NIS and TMSOTf
to give 22 in 89% yield.20
Figure 4. Visual comparison between resin treated with the unreactive
compound 17 (left) and the reactive 16 (right) illuminated with long wave
UV-radiation (365 nm). The resin treated with 16 shows a strong
fluorescence.
Compound 22 was coupled to the thiol resin by the standard
procedure. The benzoyl protecting groups were removed by

U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
2425
propose that the reaction follows a reversible carbanion
elimination (E1cB)R, followed by a fast addition of the
nucleophile. We have also shown that 2-bromoethyl
glycosides can be coupled to solid supported thiols and
thereby be used for synthesis of glycoconjugates on solid
support.
5. Experimental
5.1. General
The structures of all new compounds were determined by
careful NMR analysis, including COSY, NOESY, HET-
COR, and long-range HETCOR. NMR-spectra were
recorded with 300 and 400 MHz instruments. Chemical
shifts are given in ppm downfield from the signal for Me4Si,
with reference to internal CHCl3 or MeOH. All new
compounds were determined to be O95% pure by 1H
NMR spectroscopy. Molecular sieves were activated by
heating under vacuum. CH2Cl2 and MeCN were dried by
distillation from CaH2, DMF was distilled. Column
chromatography was performed on SiO2 (Matrex LC-gel;
60A, 35-70 MY, Grace), and TLC on Merck SiO2 60 F256
.
3-(3-Mercaptophenyl)propanamidomethylpolystyrene was
purchased from Argonaut Technologies. Compounds 4,15
8,15 17,17 and 1818 were prepared as described in the
literature. Compounds 3 and 15 are commercially available.
Scheme 6. (a) AcOH (80%, aq), 90 8C. (b) CH2Cl2, pyridine, BzCl, Tf2O,
then NaN3, DMF. (c) NaOMe-MeOH, 2 h, then BzCl, pyridine, DMAP
overnight. (d) CH2Cl2, 2-bromoethanol, NIS, TMSOTf, MS AW-300.
5.1.1. 2-(Phenylsulfonyl)ethyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (1). To a solution of 5 (490 mg,
0.93 mmol) in EtOAc (32 mL) was added mCPBA (60%,
590 mg) and the resulting mixture was stirred at room
temperature. After 30 min, the mixture was filtered through
a short column of alumina, concentrated, and chromato-
graphed (SiO2, heptane–EtOAc, 1:2) to give 1 as a white
solid (512 mg, 98%). [a]2D0ZK9.4 (c 1.2, CHCl3). 1H NMR
(CDCl3): d 7.55–8.00 (m, 5H, Ar), 5.17 (t, 1H, JZ9.5 Hz,
H-3), 5.01 (t, 1H, JZ9.8 Hz, H-4), 4.83 (dd, 1H, JZ9.6,
8.0 Hz, H-2), 4.51 (d, 1H, JZ8.0 Hz, H-1), 4.23 (dd, 1H,
JZ12.3, 5.0 Hz, H-6), 4.09–4.16 (m, 2H, H-6, CH2), 3.98–
4.06 (m, 1H, CH2), 3.68 (ddd, 1H, JZ10.0, 5.0, 2.4 Hz,
H-5), 3.35–3.50 (m, 2H, CH2), 2.10, 2.04, 2.03, 1.99 (s, 3H
each, OAc). 13C NMR (CDCl3): d 170.79, 170.37, 169.60,
169.58, 139.71, 134.15, 129.52, 128.24, 72.79, 72.12,
71.05, 68.39, 63.28, 62.01, 56.38, 20.94, 20.89, 20.78.
HRMS calcd for C22H28O12S (MCNa) 539.1199, found
539.1206.
treatment with NaOMe–MeOH (0.05 M) for 1 h. The azide
was then reduced using DTT–DBU–DMF21 and condensed
with 2-naphthoyl chloride. The sulfide was then oxidized
to the sulfone and treated with NaOMe–MeOH–CH2Cl2
to give compound 23 as an anomeric mixture in 27%
yield after purification, a recovery comparable to other
methods for synthesis of glycoconjugates on solid support
(Scheme 7).2
5.1.2. D-Glucose (3). To a solution of 1 (15 mg,
0.029 mmol) in MeOH (1.28 mL) was added NaOMe
(0.067 mL, 1 M in MeOH) and the resulting mixture was
stirred at room temperature. After 56 h AcOH (5% in
MeOH) was added until neutral solution (moist pH-paper).
The mixture was concentrated and chromatographed
(SiO2, CH2Cl2–MeOH–H2O, 66:33:4/10:20:1) to give
3 as a white solid (4.9 mg, 94%) and 6 as a clear oil (5.8 mg,
99%).
Scheme 7. (a) DMF, DBU, thiol resin. (b) DMF, DBU, MeI. (c) NaOMe-
MeOH-CH2Cl2 (0.05 M). (d) DTT, DMF, DBU. (e) DMF, pyridine, 2-
naphthoyl chloride. (f) mCPBA, CH2Cl2. (g) NaOMe-MeOH, CH2Cl2
(0.2 M).
4. Conclusion
5.1.3. 2-(Phenylthio)ethyl 2,3,4,6-tetra-O-acetyl-b-D-glu-
copyranoside (5). To a solution of 2-bromoethyl-2,3,4,6-
tetra-O-acetyl-b-D-glucopyranoside (4) (92 mg, 0.20 mmol)
in DMF (4 mL) were added thiophenol (0.038 mL,
We have shown that 2-bromoethyl glycosides can easily be
transformed into sulfones which can be cleaved by
treatment with NaOMe–MeOH to yield hemiacetals. We

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U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
0.36 mmol) and Cs2CO3 (120 mg, 0.36 mmol) and the
resulting mixture was stirred at room temperature. After 2 h
the reaction mixture was diluted with CH2Cl2, washed with
water, dried (MgSO4), concentrated, co-concentrated with
toluene and chromatographed (SiO2, toluene–acetone, 10:1)
to give 5 as a white solid (93 mg, 95%). [a]2D0ZK9.1 (c 1.1,
CHCl3). 1H NMR (CDCl3): d 7.10–7.30 (m, 5H, Ar), 5.13 (t,
1H, JZ9.5 Hz, H-3), 5.01 (t, 1H, JZ9.8 Hz, H-4), 4.93 (dd,
1H, JZ9.6, 8.0 Hz, H-2), 4.45 (d, 1H, JZ8.0 Hz, H-1), 4.17
(dd, 1H, JZ12.3, 4.8 Hz, H-6), 4.05 (dd, 1H, JZ12.3,
2.4 Hz, H-6), 3.94 (ddd, 1H, JZ10.4, 7.7, 5.5 Hz, CH2),
3.57–3.65 (m, 2H, H-5, CH2), 2.97–3.07 (m, 2H, CH2), 2.00,
1.98, 1.95, 1.94 (s, 3H each, OAc). 13C NMR (CDCl3): d
170.86, 170.49, 169.60, 135.67, 129.84, 129.25, 126.65,
101.22, 72.93, 72.06, 71.35, 68.87, 68.54, 62.09, 33.45,
20.94, 20.82, 20.80. HRMS calcd for C22H28O10S (MCNa)
507.1301, found 507.1300.
1H, JZ9.6, 8.0 Hz, H-2), 4.47 (d, 1H, JZ8.0 Hz, H-1), 4.24
(dd, 1H, JZ12.3, 4.8 Hz, H-6), 4.12 (dd, 1H, JZ12.3,
2.3 Hz, H-6), 3.88–3.95 (m, 1H, CH2), 3.65–3.70 (m, 2H,
H-5, CH2), 3.10–3.25 (m, 2H, CH2), 2.09, 2.03, 2.02, 2.00
(s, 3H each, OAc), 2.00–2.05 (m, 2H, CH2). 13C NMR
(CDCl3): d 170.86, 170.43, 169.61, 169.54, 133.99, 129.57,
128.18, 100.90, 72.89, 72.08, 71.36, 68.48, 67.70, 62.03,
53.06, 23.34, 20.95, 20.87, 20.80. HRMS calcd for
C23H30O12S (MCNa) 553.1356, found 553.1346.
5.1.7. 3-Phenylsulfonyl-propyl b-D-glucopyranoside (11).
Compound 10 (23 mg, 0.040 mmol) was dissolved in
NaOMe–MeOH (1 M, 1 mL) and the resulting mixture
was stirred at room temperature. After 24 h, AcOH (5% in
MeOH) was added until neutral solution (moist pH-paper).
The mixture was concentrated and chromatographed (SiO2,
CH2Cl2–MeOH–H2O, 66:33:4) to give 11 as a clear oil
(16 mg, 99%). [a]D20ZK14.2 (c 0.5, MeOH). 1H NMR
(CD3OD): d 7.60–7.95 (m, 5H, Ar), 4.19 (d, 1H, JZ7.8 Hz,
H-1), 3.94 (dt, 1H, JZ10.1, 5.9 Hz, CH2), 3.84 (dd, 1H, JZ
12.0, 2.0 Hz, H-6), 3.60–3.67 (m, 2H, H-6, CH2), 3.20–3.45
(m, 5H, H-3, H-4, H-5, CH2), 3.14 (dd, 1H, JZ9.0, 7.9 Hz,
H-2), 1.92–2.00 (m, 2H, CH2).13C NMR (CD3OD): d
140.65, 135.17, 130.69, 129.27, 101.45, 78.11, 75.14, 71.71,
68.48, 62.87, 54.10, 24.69. HRMS calcd for C15H22O8S
(MCNa) 385.0933, found 385.0928.
5.1.4. Deprotection study of 2-(phenylsulfonyl)ethyl
2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (1). Com-
pound 1 (10 mg, 0.019 mmol) was dissolved in CD3OD
(1.0 mL) and the mixture was added to an NMR-tube and an
NMR-spectrum was recorded. CD3ONa (0.075 mL, 1 M in
CD3OD) was added and NMR-spectra were recorded after
1, 15, 30, 120, and 300 min, respectively. After 1 min, 1 was
completely deacylated and the shift of the anomeric proton
was 4.23 ppm. The amount cleaved product was determined
as the percentage of the integral for the NMR-signals of the
anomeric protons of 3 (5.18 and 4.62 ppm) compared to the
total integral for the anomeric protons of glucose and
deacetylated bromoethyl glycoside.
5.1.8. 2-(Phenylthio)ethyl b-D-glucopyranoside (12).
Compound 4 (120 mg, 0.25 mmol) was dissolved in
NaOMe–MeOH (0.05 M, 5 mL) and stirred for 45 min at
room temperature and then neutralized using Amberlite
IR-120 HC. The mixture was concentrated and chromato-
graphed (SiO2, CH2Cl2–MeOH 5:1) to give 12 as a white
solid (78 mg, 89%). [a]2D0ZK24.8 (c 0.9, MeOH). 1H NMR
(CD3OD): d 7.15–7.41 (m, 5H, Ar), 4.28 (d, 1H, JZ7.8 Hz,
H-1), 3.97 (ddd, 1H, JZ10.4, 8.2, 6.4 Hz, CH2), 3.85 (dd,
1H, JZ10.0, 2.1 Hz, H-6), 3.75 (ddd, 1H, JZ10.4, 8.2,
6.5 Hz, CH2), 3.66 (dd, 1H, JZ11.9, 5.3 Hz, H-6), 3.23–
3.37 (m, 3H, H-3, H-4, H-5), 3.15–3.21 (m, 3H, H-2, CH2).
13C NMR (CD3OD): d 137.42, 130.46, 130.21, 127.34,
104.69, 78.13, 75.18, 71.67, 69.73, 62.80, 33.91. HRMS
calcd for C14H20O6S (MCNa) 339.0878, found 339.0864.
5.1.5. 3-(Phenylthio)propyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (9). Thiophenol (0.055 mL, 0.38 mmol)
and Cs2CO3 (124 mg, 0.38 mmol) were added to a solution
of 8 (120 mg, 0.26 mmol) in DMF (5 mL) and the resulting
mixture was stirred at room temperature. After 1 h the
reaction mixture was diluted with CH2Cl2, washed with
water, dried (MgSO4), concentrated, co-concentrated with
toluene and chromatographed (SiO2, heptane–EtOAc, 3:1)
to give 9 as a pale yellow oil (135 mg, 96%). [a]2D0ZC3.4
(c 1.0, CHCl3). 1H NMR (CDCl3): d 7.08–7.26 (m, 5H, Ar),
5.13 (t, 1H, JZ9.5 Hz, H-3), 5.02 (t, 1H, JZ9.8 Hz, H-4),
4.93 (dd, 1H, JZ9.6, 8.0 Hz, H-2), 4.42 (d, 1H, JZ8.0 Hz,
H-1), 4.19 (dd, 1H, JZ12.3, 4.7 Hz, H-6), 4.06 (dd, 1H, JZ
12.3, 2.4 Hz, H-6), 3.88 (dt, 1H, JZ9.7, 5.5 Hz, CH2), 3.55–
3.65 (m, 2H, H-5, CH2), 2.85–3.95 (m, 2H, CH2), 2.01, 1.95
(s, 3H each, OAc), 1.93 (s, 6H, OAc), 1.75–1.90 (m, 2H,
CH2). 13C NMR (CDCl3): d 171.11, 170.71, 169.83, 169.75,
136.57, 129.45, 129.37, 126.38, 101.34, 73.22, 72.22, 71.70,
68.82, 68.35, 30.17, 29.26, 21.18, 21.05, 21.03. HRMS
calcd for C23H30O10S (MCNa) 521.1457, found 521.1455.
5.1.9. 2-(Phenylthio)ethyl 2,3,4,6-tetra-O-benzyl-b-D-
glucopyranoside (13). To a solution of 12 (69 mg,
0.22 mmol) in DMF (distilled, 3 mL) was added NaH
(60%, 90 mg) and BnBr (0.15 mL). The reaction mixture
was stirred for 1 h and then quenched by addition of MeOH
(1 mL). The mixture was then diluted with CH2Cl2, washed
with water, dried (Na2SO4), concentrated and chromato-
graphed (SiO2, heptane–EtOAc, 1:1) to give 13 as a white
waxy solid (131 mg, 89%). [a]2D0ZC15.9 (c 1.7, CHCl3).
1H NMR (CDCl3): d 7.10–7.35 (m, 25H, Ar), 4.95, 4.68
1
1
5.1.6. 3-(Phenylsulfonyl)propyl 2,3,4,6-tetra-O-acetyl-b-
D-glucopyranoside (10). To a solution of 9 (45 mg,
0.083 mmol) in EtOAc (2.5 mL) was added mCPBA
(53 mg, 0.18 mmol, 60%) and the resulting mixture was
stirred at room temperature. After 30 min, the mixture was
filtered through a short column of alumina, concentrated,
and chromatographed (SiO2, heptane–EtOAc, 1:2) to give
10 as a clear oil (46 mg, 97%). [a]2D0ZK12.4 (c 1.3,
CHCl3). 1H NMR (CDCl3): d 7.50–8.00 (m, 5H, Ar), 5.19 (t,
1H, JZ9.5 Hz, H-3), 5.06 (t, 1H, JZ9.8 Hz, H-4), 4.95 (dd,
(ABq, H each, JZ11.0 Hz, OBn), 4.90, 4.76 (ABq, H
1
each, JZ11.0 Hz, OBn), 4.79, 4.50 (ABq, H each, JZ
11.1 Hz, OBn), 4.57, 4.52 (ABq, 1H each, JZ12.1 Hz,
OBn), 4.35 (d, 1H, JZ7.8 Hz, H-1), 4.07 (ddd, 1H, JZ10.2,
7.7, 5.7 Hz, CH2), 3.55–3.75 (m, 5H, H-3, H-5, H-6, CH2),
3.38–3.45 (m, 2H, H-2, H-4), 3.10–3.21 (m, 2H, CH2). 13
C
NMR (CDCl3): d 138.78, 138.68, 138.30, 138.27, 135.27,
129.59, 129.19, 128.58, 128.42, 128.18, 128.08, 127.99,
127.87, 127.84, 126.40, 104.01, 84.82, 82.39, 77.94, 75.91,
75.22 75.08, 75.06, 73.70, 72.32, 69.03, 68.71, 33.49.

U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
2427
HRMS calcd for C42H44O6S (MCNa) 699.2756, found
699.2723.
30.10, 21.02, 20.97. HRMS calcd for C27H27BrO8 (MCNa)
581.0787, found 581.0781.
5.1.10. 2-(Phenylsulfonyl)ethyl 2,3,4,6-tetra-O-benzyl-b-
D-glucopyranoside (14). To a solution of 13 (73 mg,
0.11 mmol) in EtOAc (4 mL) was added mCPBA (60%,
70 mg) and the resulting mixture was stirred at room
temperature. After 30 min, the mixture was filtered through
a short column of alumina to give 14 as a white solid
(75 mg, 99%). [a]D20ZC14.5 (c 1.6, CHCl3). 1H NMR
(CDCl3): d 7.82 (dd, 2H, JZ8.6, 1.3 Hz, Ar), 7.53 (dt, 1H,
JZ7.4 Hz, Ar), 7.41 (t, 1H, JZ7.7 Hz, Ar), 7.00–7.30 (m,
5.1.13. Coupling of 2-bromoethyl 2,3-di-O-acetyl-4,6-O-
(9-anthracenyl)methylene-b-D-glucopyranoside (4) or
2-(trimethylsilyl)ethyl 2,3-di-O-acetyl-4,6-O-(9-anthra-
cenyl)methylene-b-D-glucopyranoside (17) to thiol
scavenger resin. 3-(3-Mercaptophenyl)propanamido-
methylpolystyrene resin (1.54 mmol/g, 50 mg) was swelled
in DMF (0.480 mL) for 5 min and then DBU (0.020 mL)
was added and the resin was shaken for another 5 min.
Compound 16 (20 mg or 40 mg) or 17 (20 mg) was
dissolved in DMF (0.700 mL) and added to the resin.
Samples (0.010 mL) were taken from the solution at
different times and added to MeCN (0.990 mL). The
samples (0.500 mL) were diluted with MeCN (2.000 mL)
and the UV-absorbance measured at 364 nm.
1
20H, Ar), 4.80, 4.67 (ABq, H each, JZ10.9 Hz, OBn),
1
4.73, 4.45 (ABq, H each, JZ11.2 Hz, OBn), 4.56, 4.47
1
1
(ABq, H each, JZ11.3 Hz, OBn), 4.52, 4.44 (ABq, H
each, JZ12.1 Hz, OBn), 4.21 (d, 1H, JZ7.8 Hz, H-1), 4.12
(dt, 1H, JZ10.9, 6.6 Hz, CH2), 3.85 (dt, 1H, JZ10.9,
1
6.6 Hz, CH2), 3.61, 3.56 (dABq, H each, JZ10.7, 4.4,
2.1 Hz, H-6), 3.28–3.52 (m, 5H, H-3, H-4, H-5, CH2), 3.10
(t, 1H, JZ8.0 Hz, H-2). 13C NMR (CDCl3): d 138.62,
138.56, 138.20, 133.92, 129.36, 128.65, 128.62, 128.59,
128.57, 128.47, 128.15, 128.11, 128.09, 128.00, 127.94,
127.88, 103.84, 84.62, 82.31, 77.74, 76.91, 75.93, 75.22,
75.00, 73.72, 72.31, 68.87, 63.26, 56.69. HRMS calcd for
C42H44O8S (MCNa) 731.2655, found 731.2606.
5.1.14. Stability of 2-(phenylthio)ethyl 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranoside (5). Compound 5 (24 mg,
0.05 mmol) was subjected to the following conditions: (a)
5 was dissolved in pyridine (1.0 mL) and acetic anhydride
(0.8 mL) was added. The mixture was stirred for 22 h and
then co-concentrated with toluene and chromatographed
(SiO2, heptane–EtOAc, 1:1) to give 5 (24 mg, quant). (b) 5
was dissolved in NaOMe–MeOH (0.05 M, 1 mL) and
stirred for 1 h. The mixture was neutralized by addition of
Amberlite IR-120 HC and then concentrated to give 12
(16 mg, quant). (c) 5 was dissolved in MeOH saturated with
HCl and stirred for 17 h. The mixture was concentrated and
chromatographed (SiO2, CH2Cl2–MeOH, 5:1) to give 12
(15 mg, 94%). (d) 5 was dissolved in MeCN (1 mL, filtered
through Al2O3) and a,a-dimethoxytoluene (0.10 mL) and
pTSA (cat) were added. The mixture was stirred for 17 h,
Et3N (0.050 mL) was added and the mixture was co-
concentrated with toluene and chromatographed (SiO2,
heptane–EtOAc, 1:1) to give 5 (24 mg, quant). (e) 5 was
dissolved in AcOH (80%, 3 mL) and stirred at 90 8C for 3 h.
The mixture was co-concentrated with toluene to give 5
(23 mg, 95%). (f) 5 was dissolved in AcOH (3 mL) and Pd–
C (10%, 25 mg) was added. The mixture was pressurized
with H2 (500 psi) for 2 h and then filtered through Celite and
concentrated to give 5 (20 mg, 84%). (g) 5 was dissolved in
CH2Cl2 (2 mL) and BF3$OEt2 (0.019 mL, 3 equiv) was
added. The mixture was stirred for 1 h, then quenched by
addition of Et3N (0.040 mL). The mixture was then co-
concentrated with toluene and chromatographed (SiO2,
heptane–EtOAc, 1:1) to give 5 (24 mg, quant, a–b 1:5). (h)
5 was dissolved in CH2Cl2 (2 mL) and MS AW-300 (50 mg)
was added and the mixture was cooled down to 0 8C, under
Ar. NIS (16 mg) was added, the mixture was stirred for
10 min and then TfOH (cat) was added. The mixture was
stirred for another 10 min at 0 8C and then quenched by
addition of Et3N (0.10 mL), concentrated and chromato-
graphed (SiO2, heptane–EtOAc, 1:1) to give 5 (24 mg, quant).
5.1.11. 2,3,4,6-Tetra-O-benzyl-D-glucose (15). To a solu-
tion of 14 (58 mg, 0.082 mmol) in CH2Cl2 (2 mL) was
added NaOMe–MeOH (1 M, 2 mL) and the mixture was
stirred for 22 h and then neutralized using Amberlite IR-120
HC. The mixture was concentrated and purified on
Sephadex LH-20 (CH2Cl2–MeOH 1:1) to give 15 as a
white solid (33 mg, 74%) and 6 as a clear oil (7 mg, 43%).
5.1.12. 2-Bromoethyl 2,3-di-O-acetyl-4,6-O-(9-anthra-
cenyl)methylene-b-D-glucopyranoside (16). To a solution
of 4 (600 mg, 1.32 mmol) in MeOH (10 mL) and CH2Cl2
(5 mL) was added NaOMe–MeOH (1 M, 0.45 mL). The
mixture was stirred for 20 min and then neutralized by
addition of AcOH (1 mL). The mixture was concentrated
and filtered through a column of SiO2 (CH2Cl2–MeOH 5:1).
The residue was then dissolved in MeCN (10 mL) and
anthraldehyde dimethyl acetal (323 mg, 1.65 mmol) and
pTSA (5 mg) were added and the mixture was stirred at
room temperature overnight protected from light and then
neutralized by addition of Et3N (1 mL) and co-concentrated
with toluene 3 times. The residue was chromatographed
(SiO2, toluene/6:1 toluene–acetone) and the crude
product was then dissolved in pyridine (5 mL) and acetic
anhydride (4 mL) was added. The mixture was stirred
overnight and then co-concentrated with toluene 3 times and
the residue was chromatographed (SiO2, heptane–EtOAc
1:1) to give 16 as a white solid (354 mg, 48%). [a]2D0Z
K70.7 (c 1.2, CHCl3). 1H NMR (CDCl3): d 8.60 (d, 2H, JZ
9.2 Hz, Ar), 8.51 (s, 1H, Ar), 8.01 (d, 2H, JZ8.3 Hz, Ar),
7.45–7.55 (m, 4H, Ar), 6.90 (s, 1H, ArCH), 5.45 (t, 1H, JZ
9.3 Hz, H-3), 5.10 (dd, 1H, JZ9.1, 7.9 Hz, H-2), 4.83 (d,
1H, JZ7.8 Hz, H-1), 4.55–4.60 (m, 1H, H-6), 4.23 (p, 1H,
JZ5.6 Hz, CH2), 3.85–4.15 (m, 4H, H-4, H-5, H-6, CH2),
3.50 (t, 2H, JZ5.6 Hz, CH2), 2.10, 1.90 (s, 3H each,
OAc*2). 13C NMR (CDCl3): d 170.31, 169.96, 131.65,
130.25, 129.89, 129.24, 126.51, 126.46, 125.13, 124.97,
101.84, 100.99, 79.52, 72.66, 71.90, 70.19, 69.80, 66.97,
5.1.15. Coupling and deprotection of 2-bromoethyl
2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (4) to thiol
scavenger resin. 3-(3-Mercaptophenyl)propanamido-
methylpolystyrene resin (1.54 mmol/g, 100 mg) was
swelled in DMF (1.0 mL) for 5 min and then DBU
(0.040 mL) was added and the resin was shaken for another
5 min. Compound 4 (35 mg, 0.5 equiv to resin substitution)

2428
U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
was dissolved in DMF (1.0 mL) and added to the resin.
After 1 h MeI (0.010 mL) was added and the resin shaken
for another 10 min and then washed with DMF, CH2Cl2,
MeOH and diethyl ether and dried under vacuum. To the
dried resin was added CH2Cl2 (2 mL) and mCPBA (70%,
70 mg) and the mixture was shaken for 30 min and then
washed with CH2Cl2, MeOH and diethyl ether and dried
under vacuum. To the dried resin were added CH2Cl2
(1 mL), MeOH (1 mL) and NaOMe–MeOH (1 M, 0.40 mL)
and the mixture was shaken overnight and then neutralized
with Amberlite IR-120 HC, filtered and washed with
MeOH. The residue was purified on Sephadex (LH-20,
CH2Cl2–MeOH, 1:1) to give 3 as a white solid (7.6 mg, a–b
1:1, 55%).
of 20 (530 mg, 1.06 mmol) in MeOH (25 mL) was added
NaOMe–MeOH (0.25 mL, 1 M) and the resulting mixture
was stirred for 5 h and then neutralized using Amberlite
IR-120 HC. The residue was dissolved in pyridine (30 mL)
and benzoyl chloride (0.45 mL, 3.88 mmol) and a catalytic
amount of DMAP was added and the solution was stirred
overnight. MeOH was added and the mixture was
concentrated and flash chromatographed (SiO2, heptane–
EtOAc, 2:1) to give 21 as a white solid (615 mg, 93%).
1
[a]2D1ZK28.3 (c 1.2, CHCl3). H NMR (CDCl3): d 8.10–
8.15 (m, 6H, Ar), 7.40–7.70 (m, 11H, Ar), 7.04 (d, 2H, JZ
8.0 Hz, Ar), (5.77 (t, 1H, JZ9.9 Hz, H-2), 5.61 (dd, 1H, JZ
9.8, 3.6 Hz, H-3), 4.91 (d, 1H, JZ10.0 Hz, H-1), 4.70, 4.68
(ABq, 1H each, JZ11.5, 7.0 Hz, H-6), 4.38 (dd, 1H, JZ3.6,
1.2 Hz, H-4), 4.17 (dt, 1H, JZ7.0, 1.2 Hz, H-5), 2.34 (s, 3H,
ArCH3). 13C NMR (CDCl3): d 166.51, 166.12, 165.57,
138.87, 134.22, 133.85, 133.76, 133.68, 130.50, 130.27,
130.25, 130.11, 129.86, 129.71, 128.98, 128.96, 128.91,
128.84, 128.64, 87.72, 75.13, 75.08, 68.32, 63.79, 61.02,
21.61. HRMS calcd for C34H29N3O7S (MCNa) 646.1624,
found 646.1617.
5.1.16. 4-Methylphenyl 2,3-di-O-acetyl-1-thio-b-D-gluco-
pyranoside (19). Compound 18 (2.63 g, 5.74 mmol) was
dissolved in AcOH (80%, aq 70 mL) and stirred at 90 8C for
2.5 h and then co-concentrated with toluene. The residue
was chromatographed (SiO2, toluene–acetone, 2:1) to give
19 as a white solid (1.98 g, 93%). [a]2D0ZK33.5 (c 1.2,
CHCl3). 1H NMR (CDCl3): d 7.40 (bd, 2H, JZ8.1 Hz, Ar),
7.17 (bd, 2H, JZ7.9 Hz, Ar), 5.06 (t, 1H, JZ9.3 Hz, H-3),
4.95 (dd, 1H, JZ9.9, 9.3 Hz, H-2), 4.72 (d, 1H, JZ10.0 Hz,
5.1.19. 2-Bromoethyl 2,3,6-tri-O-benzoyl-4-azido-4-
deoxy-b-D-galactopyranoside (22). Compound 21
(388 mg, 0.62 mmol) was dissolved in CH2Cl2 (20 mL)
and MS AW-300 (600 mg) was added and the resulting
mixture was stirred for 30 min and then cooled to 0 8C.
2-Bromoethanol (0.070 mL, 1.00 mmol), N-iodosuccini-
mide (196 mg, 0.87 mmol) and a catalytic amount of
trimethylsilyl trifluoromethanesulfonate were added and
the mixture was stirred for 10 min, then Et3N (1.0 mL) was
added. The mixture was filtered through a short SiO2-
column and then chromatographed (SiO2, heptane–EtOAc,
4:1) to give 22 as a white solid (345 mg, 89%). [a]2D1Z
1
H-1), 3.97, 3.85 (dddABq, H each, JZ12.4, 6.0, 3.4 Hz,
H-6), 3.75 (dt, 1H, JZ9.5, 4.9 Hz, H-4), 3.47 (ddd, 1H, JZ
9.6, 4.7, 3.4 Hz, H-5), 2.75 (d, 1H, JZ4.9 Hz, HO-4), 2.38
(s, 3H, ArCH3), 2.15, 2.12 (s, 3H each, OAc), 2.05 (dd,
1H, JZ7.3, 6.1 Hz, HO-6). 13C NMR (CDCl3): d 172.10,
169.95, 139.17, 133.82, 130.26, 128.32, 86.33, 79.99, 70.34,
69.73, 62.73, 21.61, 21.30, 21.27. HRMS calcd for
C17H22O7S (MCNa) 393.0984, found 393.0984.
5.1.17. 4-Methylphenyl 2,3-di-O-acetyl-4-azido-6-O-ben-
zoyl-4-deoxy-1-thio-b-D-galactopyranoside (20). Com-
pound 19 (1.00 g, 2.70 mmol) was dissolved in CH2Cl2
(5 mL) and pyridine (0.87 mL) and cooled to K78 8C under
Ar. Benzoyl chloride (0.329 mL, 2.84 mmol) was added
dropwise and the mixture was stirred at K78 8C for 30 min
and then left to retain room temperature during 60 min. The
mixture was then again cooled to K78 8C and trifluoro-
methanesulphonic anhydride (0.89 mL, 5.40 mmol) was
added dropwise. After 30 min at K78 8C the mixture was
allowed to retain room temperature during 60 min and then
diluted with CH2Cl2 and washed with satd aq NaHCO3,
dried and concentrated. The residue was dissolved in DMF
(18 mL) and NaN3 (3.60 g) was added and the mixture was
stirred overnight and then filtered (SiO2, heptane–EtOAc,
2:1) and chromatographed (SiO2, heptane–EtOAc 2:1) to
give 20 as a white solid (1.16 g, 86%). [a]2D0ZK50.2 (c 1.3,
CHCl3). 1H NMR (CDCl3): d 6.97–8.02 (m, 9H, Ar), 5.26 (t,
1H, JZ9.8 Hz, H-2), 5.12 (dd, 1H, JZ9.7, 3.7 Hz, H-3),
1
K53.0 (c 1.3, CHCl3). H NMR (CDCl3): d 8.11–7.96 m,
6H, Ar), 7.65–7.37 (m, 9H, Ar), 5.79 (dd, 1H, JZ10.3,
7.8 Hz, H-2), 5.59 (dd, 1H, JZ10.3, 3.7 Hz, H-3), 4.82 (d,
1
1H, JZ7.9 Hz, H-1), 4.67, 4.58 (dABq, H each, JZ11.4,
6.4 Hz, H-6), 4.35 (dd, 1H, JZ3.7, 1.2 Hz, H-4), 4.16 (m,
2H, H-5, CH2), 3.90 (m, 1H, CH2), 3.45 (m, 2H, CH2). 13
C
NMR (CDCl3): d 166.05, 165.70, 165.17, 133.81, 133.49,
133.24, 130.06, 129.77, 129.72, 129.26, 128.58, 128.56,
128.33, 128.13, 101.60, 73.31, 70.96, 69.59, 69.14, 62.82,
60.28, 29.57. HRMS calcd for C29H26BrN3O8 (MCNa)
646.0801, found 646.0775.
5.1.20. 4-Deoxy-4-(2-naphthoyl)-amido-D-galactose (23).
3-(3-Mercaptophenyl)propanamidomethylpolystyrene resin
(1.54 mmol/g, 100 mg) was swelled in DMF (1.0 mL) for
5 min and then DBU (0.040 mL) was added and the resin
was shaken for another 5 min. Compound 22 (48 mg,
0.5 equiv to resin substitution) was dissolved in DMF
(1.0 mL) and added to the resin. After 1 h MeI (0.050 mL)
was added and the resin shaken for another 10 min and then
washed with DMF, CH2Cl2, MeOH and diethyl ether and
dried under vacuum. The dried resin was swelled in CH2Cl2
(1 mL) and MeOH (1 mL) and NaOMe–MeOH (1 M,
0.10 mL) were added. The resin was shaken for 1 h and
then washed with MeOH and CH2Cl2. DTT (76 mg) in DMF
(1 mL) was added followed by DBU (0.010 mL) and the
resin was shaken overnight and then washed with DMF,
CH2Cl2, MeOH and diethyl ether and dried under vacuum.
The dried resin was swelled in DMF (2 mL) and pyridine
1
4.58 (d, 1H, JZ10.0 Hz, H-1), 4.54, 4.45 (ABq, H each,
JZ11.5, 5.4 Hz, H-6), 4.05–4.12 (m, 1H, H-4), 3.93 (dt, 1H,
JZ5.7, 1.3 Hz, H-5), 2.27 (s, 3H, ArCH3), 2.09, 2.08 (s, 3H
each, OAc). 13C NMR (CDCl3): d 170.57, 169.80, 166.47,
138.81, 133.86, 133.43, 130.22, 130.12, 129.81, 128.94,
87.48, 74.85, 74.51, 67.79, 63.74, 60.71, 21.60, 21.28,
20.43. HRMS calcd for C24H25N3O7S (MCNa) 522.1311,
found 522.1308.
5.1.18. 4-Methylphenyl 4-azido-2,3,6-tri-O-benzoyl-4-
deoxy-1-thio-b-D-galactopyranoside (21). To a mixture

U. Ellervik et al. / Tetrahedron 61 (2005) 2421–2429
2429
2. Seeberger, P. H.; Haase, W. Chem. Rev. 2000, 100, 4349–4393
(0.20 mL) and 2-naphthoyl chloride (50 mg) were added.
The resin was shaken for 4 h and then washed with DMF,
CH2Cl2, MeOH and diethyl ether and dried under vacuum.
To the dried resin were added CH2Cl2 (4 mL) and mCPBA
(70%, 70 mg) and the mixture was shaken for 30 min and
then washed with CH2Cl2, MeOH and diethyl ether and
dried under vacuum. To the dried resin was added CH2Cl2
(2 mL), MeOH (2 mL) and NaOMe–MeOH (1 M, 0.80 mL)
and the mixture was shaken overnight and then neutralized
with acetic acid and washed with MeOH. The residue
was chromatographed (SiO2, CH2Cl2–MeOH 5:1) to give
23 as a complex anomeric and rotameric mixture
(6.8 mg, 27%). HRMS calcd for C17H19NO6 (MCNa)
356.1110, found 356.1123. 1H NMR can be found as
Supplementary Material. 13C NMR (CD3OD): d 170.80,
136.43, 134.22, 130.17, 192.72, 129.35, 129.10, 128.96,
128.92, 128.76, 128.12, 127.94, 125.30, 124.60, 99.71,
98.49, 71.22, 70.04, 66.41, 66.22, 65.94, 64.89, 63.43,
62.11, 55.54, 55.37.
and references therein.
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Acknowledgements
This work was supported by the Swedish Research Council.
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Supplementary data
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Supplementary data associated with this article can be
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19. Ercegovic, T.; Meijer, A.; Magnusson, G.; Ellervik, U. Org.
Lett. 2001, 3, 913–915.
20. The benzoylated analog of 19 showed severe disrupture of the
chair conformation (proven by NMR) and no attempts to
transform this compound into the azide were made.
References and notes
21. Komba, S.; Werdelin, O.; Jensen, T.; Meldal, M. J. Pept. Sci.
2000, 6, 585–593.
1. Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149–2154.