Practical synthesis of the 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucosides of Fmoc-serine and Fmoc-threonine and their benzyl esters

Article abstract of DOI:10.1016/S0008-6215(03)00071-5

Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding β-glycosides in good yields (64 and 62%, respectively).

Full text of DOI:10.1016/S0008-6215(03)00071-5

Carbohydrate Research 338 (2003) 1039–1043
www.elsevier.com/locate/carres
Practical synthesis of the
2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b- -glucosides of
D
Fmoc-serine and Fmoc-threonine and their benzyl esters
Ivone Carvalho,a,b,c Shona L. Scheuerl,b K.P. Ravindranathan Kartha,b,c
Robert A. Fieldb,c,*
aFaculdade de Cieˆncias Farmaceˆuticas de Ribeira˜o Preto, Uni6ersidade de Sa˜o Paulo, Ribeira˜o Preto 14040 930, Brazil
bSchool of Chemistry and Centre for Biomolecular Sciences, The Purdie Building, Uni6ersity of St Andrews, St Andrews, Fife KY16 9ST, UK
cCentre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy, Uni6ersity of East Anglia, Norwich NR4 7TJ, UK
Received 21 October 2002; accepted 10 February 2003
Abstract
Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-
a- -glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding b-glycosides in good yields (64 and 62%,
D
respectively). Direct coupling of the commercially available Fmoc-Ser-OH and Fmoc-Thr-OH carboxylic acids under similar
conditions gave the corresponding b-glycosides, possessing free carboxyl groups, in moderate yields (50 and 40%, respectively).
© 2003 Elsevier Science Ltd. All rights reserved.
Keywords: Serine; Threonine; Benzyl ester; Free carboxylic acid; Mercuric bromide; Glycosylation
1. Introduction
GlcNAc-Ser, by replacing the linking anomeric oxygen
by sulfur5 and carbon,6 for incorporation into gly-
copeptide probes for biochemical analyses. In addition,
as characterisation of the key O-GlcNAc b-N-acetylglu-
cosaminidase progresses7 there is a need to consider
synthetic routes to analogues of O-linked b-GlcNAc to
probe the molecular basis of its recognition and
cleavage.
Dynamic O-glycosylation of nuclear and cytoplasmic
proteins is thought to play a complimentary and/or
orthogonal role to protein phosphorylation in the regu-
lation of signal transduction processes. Proteins ranging
from the myc-oncogene product and tumour suppressor
p53 to the beta-amyloid precursor protein, RNA poly-
merase II and a variety of chromatin- and microtubule-
associated proteins are all subject to reversible addition
of b-linked N-acetylglucosamine.1,2 Similarly in plants,
response to giberellins is thought to be at least partially
regulated by the action of the spindly O-GlcNAc trans-
ferase.3 Since the addition of O-GlcNAc often occurs at
potential phosphorylation sites, the typical site-directed
mutagenesis approach to investigate the role of either
process is complicated.4 Efforts have therefore been
made to synthesise non-hydrolysable analogues of O-
Although 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-
-glucopyranosyl chloride (1) is often used as a glycosyl
D
donor for glycosylation of simple alcohols, there are
some limitations due to its low reactivity and the paral-
lel formation of a relatively stable oxazoline by-
product, 2.8 Alternatively, 1,2-trans-glycosides can be
prepared via an acid catalysed reaction of the same
oxazoline derivative 2.9 For glycosyl-amino acid synthe-
sis, the coupling of appropriately protected glycosyl
halides with the protected amino acid in the presence of
a promoter affords the desired products in variable
yield and/or with poor stereoselectivity.10 Even a simple
change of ester protecting group can have a major
impact on reaction yield.8a The oxazoline procedure has
therefore been widely used for glycosyl-amino acid
* Corresponding
author.
Tel.:
+44-1603-593983;
fax: +44-1603-592003
E-mail address: r.a.field@uea.ac.uk (R.A. Field).
0008-6215/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0008-6215(03)00071-5

1040
I. Car6alho et al. / Carbohydrate Research 338 (2003) 1039–1043
synthesis,11 although efforts continue to be made to
improve this procedure12 and to devise practical alter-
natives.13 Having considered the various different build-
ing blocks, we chose to revisit the stereoselective
out in refluxing benzene in the presence of mercuric
cyanide alone. This procedure is described for the cor-
responding N-benzyloxycarbonyl-protected acceptor in
70% yield, although the methyl ester gave only 34% of
the desired adduct.8a On the other hand, glycosylation
was successfully achieved using mercuric bromide as the
sole promoter. On refluxing a 1,2-dichloroethane solu-
tion of glycosyl chloride 1 (2 equivalents) and protected
serine 3 or threonine 4, in the presence of mercuric
bromide (1.1 equivalents) N-(9-fluorenylmethoxycar-
formation of the b-
available glycosyl donor 2-acetamido-2-deoxy-3,4,6-tri-
O-acetyl-a- -glucopyranosyl chloride (1). Herein we
D-GlcNAc-Ser/Thr using the readily
D
report improvements to the preparation of 1, together
with its coupling to appropriately protected serine and
threonine building blocks (Fig. 1).
bonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-b-
glucopyranosyl)- -serine benzyl ester (5) and N-(9-
fluorenylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-
tri-O-acetyl-b- -glucopyranosyl)- -threonine benzyl es-
D-
L
2. Results and discussion
D
L
The preparation of 2-acetamido-2-deoxy-3,4,6-tri-O-
ter (6) were obtained in 64 and 62% yield, respectively.
The b configuration of the glycosidic bond was estab-
lished in both cases from 1H and 13C NMR spectra
(serine glycoside 5: H-1 doublet at l 4.67, J1,2 8.4 Hz
and C-1 at l 100.6 ppm; threonine glycoside 6: H-1
doublet at l 4.65, J1,2 8.1 Hz and C-1 at l 98.50 ppm).
The reaction conditions described proved effective over
a range of scales (0.5–55 mmol glycosyl chloride) with-
out significant changes in the overall yield. We suspect
that the oxazoline may be an intermediate in the reac-
tion process, but we have so far been unable to confirm
this.
Although we have shown iodine in the presence of
DDQ to be an effective promoter system for glycosyla-
tion of simple alcohols with glycosyl chloride donor 1,17
attempts to use this system with acceptors 3 and 4
proved fruitless (yields ꢀ10%, mixed anomers), as did
the use of iodine monochloride and iodine monobro-
mide (yields ꢀ20%, mixed anomers).18
acetyl-a- -glucopyranosyl chloride (1) has been a litera-
D
ture standard14 for many years and routinely gives
robust, but often not exceptional, yields even in inexpe-
rienced hands. We have found that, as for the prepara-
tion of the corresponding sialic acid glycosyl chloride,15
presaturating the acetyl chloride reaction medium used
to effect O-acetylation and concurrent glycosyl chloride
formation with anhydrous hydrogen chloride increases
reaction rates and generally leads to improved yields
(15–20% improvement) of glycosyl chloride 1.
Classical Helferich glycosylation conditions16 were
initially investigated for coupling known13c Fmoc-Ser-
OBn 3 and Fmoc-Thr-OBn 4 to give the target glycosyl
serine and threonine benzyl esters, 5 and 6, respectively.
Glycosylation reactions were attempted under various
reaction conditions with mercuric cyanide and mercuric
bromide. Using this approach, serine b-glycoside 5 was
obtained in poor yield (10%). A slight improvement in
yield was obtained (23%) when the reaction was carried
Fig. 1. Glycosylation of Fmoc-Ser/Thr-OBn/OH.

I. Car6alho et al. / Carbohydrate Research 338 (2003) 1039–1043
1041
For further use in solid phase glycopeptide synthesis,
the a-amino acid carboxyl groups of 5 and 6 need to be
released, for example by hydrogenolysis, to give car-
boxylic acids 9 and 10. In order to cut out this extra
chemical step and the associated chromatography, and
for comparison with oxazoline chemistry,9 the direct
coupling of glycosyl chloride 1 to serine and threonine
derivatives possessing free carboxyl groups (i.e. 7 and 8,
respectively) was investigated. Under the conditions
described above for the corresponding benzyl esters,
Fmoc-Ser-OH 7 and Fmoc-Thr-OH 8 gave the corre-
sponding b-glycosides 9 and 10 in 50 and 40% yield,
respectively. Although the yields are not high, the
target glycosyl amino acid building blocks can be ac-
cessed directly from readily available protected amino
acids under relatively mild conditions. In addition,
formation of the glycosyl halide donor reagent is essen-
tially stereospecific and high yielding, whereas access to
the alternative oxazoline donor generally requires prior
synthesis of the anomeric b-acetate, which can be low
yielding.19
(3) (104 mg, 0.25 mmol) in 1,2-dichloroethane (2.0 mL)
was refluxed with mercuric bromide (198 mg, 0.55
mmol) for 9 h, when TLC [Hex–EtOAc (7:3)] showed
the reaction to be complete. The resulting amber mix-
ture was concentrated in vacuo and the residue was
purified by a silica gel column chromatography [eluent:
EtOAc–Hex (7:3)]. The desired glycoside 5 (119 mg,
64%) was obtained as an amorphous solid; [h]D −4.6
(c 1, CHCl3) (Lit.,13c [h]D −3.7); Rf 0.25 [EtOAc–Hex
(7:3)]; lH (CDCl3, 300 MHz) 7.77 (2 H, d, J 7.8, Fmoc
Ph), 7.64 (2H, d, J 7.8, Fmoc Ph), 7.40–7.26 (9 H, m,
Fmoc Ph, Bn), 5.81 (1 H, d, J 8.7, NHThr), 5.35 (1 H,
d, J 8.4, NHAc), 5.25 (1 H, t, J3,4 9.6, H-3), 5.20 (2 H,
AB, OCH2Ph), 5.02 (1 H, t, J3,4 10, H-4), 4.67 (1 H, d,
J1,2 8.4, H-1), 4.55–4.38 (3 H, m, CH2 Fmoc, CH Ser),
4.28–4.19 (3 H, m, H-6, CH Fmoc, CH2a Ser), 4.08 (1
H, dd, J 2.2, J6,6% 12.3, H-6%), 3.85 (1 H, dd, J 2.7, J
10.8, CH2b Ser), 3.70 (1 H, apparent t, J1,2, J2,3 10, H-2)
3.64–3.59 (1 H, m, H-5), 2.04, 2.03, 2.02, 1.82 (12 H,
4×s, COCH3); lC (CDCl3, 75 MHz) 170.8, 170.7,
169.5, 169.4 (COCH3, COCH2Ph), 156.1 (CO Fmoc),
143.6, 143.7, 141.3 (Cquat. Fmoc), 135.3 (Cquat.
OCH2Ph) 128.5, 128.4, 128.2, 127.7, 127.1, 125.1, 119.9
(Fmoc Ph, CHPh), 100.6 (C-1), 71.9, 71.7 (C-5, C-3),
68.9, 68.3 (C-4, CH2 Ser), 67.3 (OCH2Ph), 66.7 (CH2
Fmoc) 61.8 (C-6), 54.6, 54.1 (C-2, CH Ser), 47.0 (CH-
Fmoc), 22.8, 20.7 (COCH3). ESIMS found m/z
764.3025 [M+NH+4 ]. Calcd for C39H42N2O13·NH4
764.3031.
In summary, in our hands HgBr2-mediated glycosyla-
tion with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-D-
glucopyranosyl chloride (1) is at least competitive with
the oxazoline procedure for the synthesis of the O-
acetylated benzyl esters and free acids of b-
D-GlcNAc-
Ser and b- -GlcNAc-Thr.
D
3. Experimental
3.2. N-(9-Fluorenylmethoxycarbonyl)-(2-acetamido-2-de-
oxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl)-L-threonine
benzyl ester (6)
Thin-layer chromatography (TLC) was performed on
Silica Gel 60 F254 (Merck) detected by immersion in a
5% ethanolic solution of H2SO4, followed by heating
(\100 °C). Normal-phase column chromatography
was performed using Silica Gel 60 (0.063–0.200 mm).
Concentration of organic extracts was typically carried
out below 40 °C and at water pump pressure. Unless
otherwise stated, NMR spectra were obtained in CDCl3
(referenced to l 77.0 or residual CHCl3 at l 7.27 ppm
for 13C and 1H, respectively) or D2O (referenced to
A mixture of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-
-glucopyranosyl chloride (1, 181 mg, 0.50 mmol) and
N-(9-fluorenylmethoxycarbonyl)- -threonine benzyl es-
D
L
ter 4 (108 mg, 0.25 mmol) in 1,2-dichloroethane (2.0
mL) was treated as described for the preparation of
glycoside 5. The residue was eluted from a column of
silica gel with EtOAc–Hex (7:3) to give the product 6
(117 mg, 0.16 mmol, 62%) as an amorphous solid; [h]D
−15.6 (c 1, CHCl3); Rf 0.26 [EtOAc–Hex (7:3)]; lH
(CDCl3, 400 MHz) 7.76 (2 H, d, J 7.6, CH Fmoc Ph),
7.64 (2 H, d, J 7.8, CH Fmoc Ph), 7.41–7.26 (9 H, m,
Fmoc Ph, OCH2Ph), 5.83 (1 H, d, J 9.1, NHThr), 5.54
(1 H, d, J 8.4, NHAc), 5.25 (1 H, apparent t, J2,3 9.9,
H-3), 5.21, 5.14 (2 H, AB, JAB 12.2, OCH2Ph), 5.00 (1
H, t, J3,4 9.9, H-4), 4.65 (1 H, d, J1,2 8,1, H-1), 4.47–
4.40 (3 H, m, CH2 Fmoc, bCHThr), 4.35 (1 H, dd, J
7.3, J 10.7, aCHThr), 4.24 (1 H, t, J 7.3, CHFmoc),
4.19 (1 H, dd, J5,6 4.4, J6,6% 12.3, H-6), 4.02 (1 H, dd,
J5,6% 2.2, J6,6%, H-6%), 3.67 (1 H, dd, J1,2, J2,3, H-2),
3.51–3.47 (1 H, m, H-5), 2.03, 2.02, 1.99, 1.93 (12 H,
4×s, COCH3), 1.20 (3 H, d, J 6.3, CH3 Thr); lC
(CDCl3, 100 MHz) 170.9, 170.6, 170.4, 170.0 (COCH3),
1
added acetone at l 31.00 or 2.25 ppm for 13C and H,
respectively). Dichloroethane was freshly distilled from
CaH2.
2-Acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-D-
glucopyranosyl chloride (1) was prepared essentially as
described by Horton, except that the acetyl chloride
reaction medium was presaturated with gaseous hydro-
gen chloride prior to use.
3.1. N-(9-Fluorenylmethoxycarbonyl)-(2-acetamido-2-de-
oxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl)-L-serine ben-
zyl ester (5)
A mixture of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-
-glucopyranosyl chloride (1, 181 mg, 0.50 mmol) and
N-(9-fluorenylmethoxycarbonyl)- -serine benzyl ester
D
L

1042
I. Car6alho et al. / Carbohydrate Research 338 (2003) 1039–1043
169.4 (COCH2Ph), 156.8 (CO Fmoc), 144.0, 141.3
(Cquat. Fmoc Ph), 135.5 (Cquat. OCH2Ph), 128.6,
128.5, 128.3, 127.7, 127.1, 125.5, 119.9 (CH Ph), 98.5
(C-1), 74.5 (bCHThr), 71.9, 71.7 (C-5, C-3), 68.5 (C-4),
67.3 (OCH2Ph, CH2 Fmoc), 61.9 (C-6), 58.7
(aCHThr), 55.3 (C-2), 47.3 (CH Fmoc), 23.3, 20.7,
20.5, 20.6 (COCH3), 17.0 (CH3 Thr). ESIMS found
m/z 778.3187 [M+NH+4 ]. Calcd for C40H44N2O13·NH4
778.3187.
−14.4 (c 1, in MeOH)(Lit.,9 [h]D+14.7); Rf 0.55
[CHCl3–MeOH (30:1)]; lH (CDCl3, 270 MHz) 7.73 (2
H, d, J 7.3, CH Fmoc Ph), 7.61 (2 H, d, J 6.6, CH
Fmoc Ph), 7.38–7.24 (4 H, m, CH Fmoc Ph), 6.12 (1
H, d, J 9.2, NH), 6.03 (1 H, d, J 9.2, NH), 5.26 (1 H,
t, J2,3 9.6, H-3), 5.09 (1 H, t, J3,4 9.6, H-4), 4.64 (1 H,
d, J1,2 8.3, H-1), 4.50–3.60 (9 H, m, CH2 Fmoc, 2 CH
Thr, H-6, CH Fmoc, H-6%, H-2, H-5), 2.04, 1.98, 1.97,
1.93 (12 H, m, COCH3), 1.18 (3 H, d, J 6.3, CH3 Thr);
lC (CDCl3, 67.5 MHz) 171.3, 170.9, 170.8, 169.3
(COCH3), 156.8 (CO Fmoc), 143.7, 141.1 (Cquat.),
127.6, 127.0, 125.1, 119.9 (CH Ph), 99.4 (C-1), 71.7,
71.5, 70.9, 68.2, 67.3 (C-3, C-4, C-5, 2 CH Thr, CH2
Fmoc), 62.0 (C-6), 52.3 (C-2), 47.0 (CH Fmoc), 22.9,
20.8, 20.7, 20.5 (COCH3), 17.3 (CH3 Thr) (NMR data
in accord with the literature20); ESIMS found m/z
671.2453 [M+NH+4 ]. Calcd for C40H44N2O13 671.2452.
The optical rotation noted above for compound 10 is at
odds with the literature.9 However, the sense of the
rotation we report herein is in keeping with that of the
corresponding pentafluorophenyl ester.21
3.3. N-(9-Fluorenylmethoxycarbonyl)-(2-acetamido-2-de-
oxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl)-L-serine (9)
A mixture of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-
-glucopyranosyl chloride (1, 181 mg, 0.50 mmol) and
commercial N-(9-fluorenylmethoxycarbonyl)- -serine
D
L
(7, 82 mg, 0.25 mmol) in 1,2-dichloroethane (1.5 mL)
was treated as described for the preparation of 5. The
reaction mixture was washed with aq soln of 3% EDTA
and the organic layer dried over MgSO4 and concen-
trated. The residue was eluted from a column of silica
gel with CHCl3–AcOH (8:0.3 and then 8:0.6) to give
the product 9 (83 mg, 50%) as an amorphous solid; [h]D
−14.8 (c 0.29, CHCl3)(Lit.,13c [h]D −14.7); Rf 0.45
[CHCl3–MeOH–AcOH (8:1:0.1)]; lH (CDCl3/CD3OD,
400 MHz) 7.78 (2 H, d, J 7.3, Fmoc Ph), 7.64 (2 H, d,
J 7.6, Fmoc Ph), 7.43–7.31 (4 H, m, Fmoc Ph), 5.20 (1
H, t, J2,3 9.8, H-3), 5.02 (1 H, t, J3,4 9.8, H-4), 4.63 (1
H, d, J1,2 8.6, H-1), 4.49 (1 H, dd, J 10.6, J 6.5,
CH2aFmoc), 4.43–4.41 (1 H, m, CH Ser), 4.39 (1 H, dd,
J 10.6, J 6.8, CH2bFmoc), 4.27–4.17 (2 H, m, H-6, CH
Fmoc), 4.19 (1 H, dd, J 10.9, J 4.0, CH2a Ser), 4.12 (1
H, dd, J5,6% 2.1, J6,6% 12.2, H-6%), 3.89 (1 H, dd, J 10.9, J
3.3, CH2b Ser), 3.84 (1 H, dd, J1,2, J2,3, H-2), 3.69 (1 H,
ddd, J4,5 9.1, J5,6 4.5, J5,6%, H-5), 2.08, 2.03, 2.02, 1.86
(12 H, 4×s, COCH3); lC (CDCl3/CD3OD, 100 MHz)
172.0, 171.1, 170.6, 169.8 (COCH3), 160.5 (CO Fmoc),
143.7, 141.2 (Cquat), 127.7, 125.0, 119.9 (CH Ph),
100.7 (C-1), 72.5 (C-3), 71.7 (C-5), 69.0, 68.8 (C-4, CH2
Ser), 67.0 (CH2 Fmoc), 62.1 (C-6), 54.2, 54.0 (C-2, CH
Ser), 47.1 (CH Fmoc), 22.4, 20.5, 20.4 (COCH3). ES-
IMS found m/z 674.2557 [M+NH+4 ]. Calcd for
C40H44N2O13·NH4 674.2561.
Acknowledgements
These studies were supported by the MRC and the
Weston Foundation. Support in the form of a research
leave fellowship from FAPESP is gratefully acknowl-
edged (IC). We thank Julia Bilke for performing some
preliminary glycosylation experiments. We are indebted
to the EPSRC Mass Spectrometry Service Centre,
Swansea for invaluable support.
References
1. Wells, L.; Vosseller, K.; Hart, G. W. Science 2001, 291,
2376–2378.
2. Zachara, N. E.; Hart, G. W. Chem. Re6. 2002, 102,
431–438.
3. Thornton, T. M.; Swain, S. M.; Olszewski, N. E. Trends
Plant Sci. 1999, 4, 424–428.
4. Comer, F. I.; Hart, G. W. Biochemistry 2001, 40, 7845–
7852.
5. Ohnishi, Y.; Ichikawa, M.; Ichikawa, Y. Bioorg. Med.
Chem. Lett. 2000, 10, 1289–1291.
6. Ohnishi, Y.; Ichikawa, Y. Bioorg. Med. Chem. Lett. 2002,
12, 997–999.
3.4. N-(9-Fluorenylmethoxycarbonyl)-(2-acetamido-2-de-
oxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl)-L-threonine
(10)
7. Wells, L.; Gao, Y.; Mahoney, J. A.; Vosseller, K.; Chen,
C.; Rosen, A.; Hart, G. W. J. Biol. Chem. 2002, 277,
1755–1761.
8. For example: (a) Garg, H.G.; Jeanloz, R.W. Carbohydr.
Res., 1976, 49, 482–488; (b)Vafina, M.G.; Kim., A.;
Molodstov, N.V. Carbohydr. Res., 1978, 64, 334–338.
9. Arsequell, G.; Krippner, L.; Dwek, R.; Wong, S. Y. C.
Chem. Commun. 1994, 2383–2384.
A mixture of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-a-
-glucopyranosyl chloride (1, 181 mg, 0.50 mmol) and
commercial N-(9-fluorenylmethoxycarbonyl)-
threonine (8, 86 mg, 0.25 mmol) in 1,2-dichloroethane
(1.5 mL) was treated as described for the preparation of
9. The residue was eluted from a column of silica gel
with CHCl3–AcOH (8:0.3 and then 8:0.6) to give the
product 10 (67 mg, 40%) as an amorphous solid; [h]D
D
L-
10. Reviewed in Taylor, C. M. Tetrahedron 1998, 54, 11317–
11362.

I. Car6alho et al. / Carbohydrate Research 338 (2003) 1039–1043
1043
17. Kartha, K. P. R.; Aloui, M.; Field, R. A. Tetrahedron
Lett. 1996, 37, 8807–8810.
18. Kartha, K. P. R.; Field, R. A. Tetrahedron Lett. 1997, 38,
8233–8237.
19. Conchie, J.; Levvy, G. A. Methods Carbohydr. Chem.
1963, 2, 332–335.
20. (a) Seitz, O.; Wong, C.-H. J. Am. Chem. Soc. 1997, 119,
8766–8776;
11. For example Pohl, T.; Waldmann, H. J. Am. Chem. Soc.
1997, 119, 6702–6710.
12. Wittmann, V.; Lennartz, D. Eur. J. Org. Chem. 2002,
1363–1367.
13. For example: (a) Meinjohanns, E.; Meldal, M.; Bock, K.
Tetrahedron Lett., 1995, 36, 9205–9208; (b) Saha, U.K.;
Schmidt, R.R. J. Chem. Soc., Perkin Trans. 1, 1997,
1855–1860; (c) Mitchell, S.A.; Pratt, M.A.; Hruby, V.J.;
Polt, R. J. Org. Chem., 2001, 66, 2327–2342.
14. Horton, D. Methods Carbohydr. Chem. 1972, 6, 282–
285.
(b) Simanek, E. C.; Huang, D.-H.; Pasternack, L.;
Machajewski, T. D.; Seitz, O.; Millar, D. S.; Dyson, H.
J.; Wong, C.-H. J. Am. Chem. Soc. 1998, 120, 11567–
11575.
15. Kuhn, R.; Lutz, P.; MacDonald, D. L. Chem. Ber. 1966,
21. (a) Vargas-Berengud, A.; Meldal, M.; Paulsen, H.; Bock,
K. J. Chem. Soc., Perkin Trans. 1 1994, 2615–2619;
(b) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Berany,
G. J. Am. Chem. Soc. 1996, 118, 3148–3155.
99, 611–617.
16. Helferich, B.; Wedemeyer, K.-F. Justus Liebigs Ann.
Chem. 1949, 563, 139–145.