Straightforward synthesis of 2-acetamido-2-deoxy -β- d -glucopyranosyl esters under microwave conditions

Article abstract of DOI:10.1055/s-0029-1218358

A straightforward synthesis of 2-acetamido-2-deoxy -β-d-glucopyranosyl esters from unprotected GlcNAc oxazoline has been achieved under catalyst-free, microwave conditions. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218358

3328
LETTER
Straightforward Synthesis of 2-Acetamido-2-deoxy-b-D-glucopyranosyl Esters
under Microwave Conditions
S
ynthesis of 2-A
c
o
etamido-2-d
s
eoxy-
b
-
D
-
glucopyranosyl
E
H
sters addoub, Nicolas Laurent, Marco M. Meloni, Sabine L. Flitsch*
Manchester Interdisciplinary Biocentre and School of Chemistry, The University of Manchester,
131 Princess Street, Manchester M1 7DN, UK
Fax +44(161)2751311; E-mail: sabine.flitsch@manchester.ac.uk
Received 10 September 2009
phenolic acid7 and nonsteroidal anti-inflammatory drugs
Abstract: A straightforward synthesis of 2-acetamido-2-deoxy-b-
D-glucopyranosyl esters from unprotected GlcNAc oxazoline has
been achieved under catalyst-free, microwave conditions.
such as ibuprofen, naproxen, and diclofenac.8
Synthesis of glycosyl esters has been achieved using cou-
pling reagents such as DCC,9 imidazole,10 by Mitsunobu
reaction,3,11 Yamaguchi anhydride derivative,12 or with
Key words: glycosyl esters, glycomimetics, GlcNAc oxazoline,
microwaves, catalyst-free
assistance of a C-2 participating neighboring group.13
A
glycosyl trichloroacetimidate has been used to synthesize
ester-linked glycosyl dopamine derivatives as potential
antiparkinsonian prodrugs.14 Besides, glycosyl esters are
sometimes encountered as side products of glycosylation
reactions.15 However, the key issue of the glycosyl ester
formation is the anomeric selectivity, often controlled by
the rate of mutarotation in a given solvent.11,16 For exam-
ple, Binkley et al.17 have studied the synthesis of penta-O-
galloyl-D-glucopyranose as a model reaction and investi-
gated conditions leading to high anomeric selectivity.
Carbohydrates, either linked to proteins, lipids, or as
polysaccharides are ubiquitous features of biomolecules
and are involved in many important functions such as cell
communication, protein stability, and activity or immuni-
ty.1 Glycoconjugates are typically referred to as O- or N-
glycosides, depending on the nature of the heteroatom
connecting the carbohydrate moiety to the aglycon. Glyc-
osyl esters, in which the sugar head is linked to the agly-
con via an ester linkage, represent a less common family
of glycosides and are encountered in natural products such
as the ellagitannin2 and phyllanthostatin3 families of anti-
tumor agents. The potent immunoadjuvant QS21-A, iso-
lated from Quillajia saponaria, is a complex saponin
glycoside in which a tetrasaccharide is attached at the C-
28 carboxylate of the triterpene moiety.4 The ovine sub-
maxillary gland mucoprotein contains 2-acetamido-2-
deoxy-D-galactosyl (GalNAc) moieties bound by an ester
linkage to the aspartic and glutamic acid side chains.5 A b-
1,3-glucan glutamate ester has recently been identified in
the fungal cell wall Pir protein of Saccharomyces cerevi-
siae.6 Acyl glucuronides are metabolite products of myco-
As part of our ongoing effort towards the synthesis of gly-
copeptides and the design of glycoarrays,18 an unexpected
outcome in the synthesis of N-acetyl-D-glucosaminyl
serine prompted us to investigate the reactivity of GlcNAc
oxazoline with carboxylic acids under microwave condi-
tions. The oxazoline of D-GlcNAc is a well-known glyco-
syl donor and has been extensively used for the
preparation of glycoconjugates in combination with nu-
merous Lewis acids.19However, when per-O-acetylated
GlcNAc oxazoline 2 (prepared by refluxing the per-O-
acetylated 2-acetamido-2-deoxy-a-D-glucopyranose 1 in
dry dichloromethane in the presence of a stoichiometric
OAc
O
AcO
AcO
NHAc
OAc
1
OAc
TMSOTf,
CH2Cl2, reflux
O
NHFmoc
NHFmoc
AcO
AcO
O
HO
OH
OH
OAc
NHAc
3a
O
O
O
AcO
AcO
30 min, 80 °C, 200 W
OAc
N
O
NHFmoc
OH
O
2
AcO
AcO
O
NHAc
O
3b
Scheme 1
SYNLETT 2009, No. 20, pp 3328–3332
x
x
.x
x
.2
0
0
9
Advanced online publication: 11.11.2009
DOI: 10.1055/s-0029-1218358; Art ID: D25309ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of 2-Acetamido-2-deoxy-b-D-glucopyranosyl Esters
3329
amount of TMSOTf)20 was reacted with N-Fmoc serine A possible explanation for this reaction is the protonation
under microwave conditions and in the absence of any of the oxazoline nitrogen first, favoring attack of the ano-
Lewis acid (Scheme 1), careful examination of the NMR meric center by the nucleophilic carboxylate15d from the
spectrum of the product 3b obtained revealed an ester b-face, thereby accounting for the complete stereoselec-
linkage between the GlcNAc and the serine in the b-con- tivity of this transformation. However, the use of acetyl
figuration instead of the O-glycosylated amino acid 3a.21
protecting groups prevented any deprotection of the sugar
moiety without cleaving the anomeric ester linkage.
Table 1 Reaction of GlcNAc-oxazoline with Carboxylic Acids
Entry
Carboxylic acid
Product and yield
OH
NHFmoc
O
O
HO
HO
1
O
O
O
FmocHN
NHAc
OH
O
O
O
5 63%
OH
OH
O
O
HO
HO
2
3
C5H11
OH
OH
O
NHAc
6 55%
O
O
HO
HO
Bu
NHAc
7 60%
OH
Cl
Cl
O
HO
HO
O
4
NHAc
O
Cl
Cl OH
8 40%
OH
OH
OH
OH
O
HO
O
HO
HO
5
6
O
NHAc
OH
O
O
O
9 45%
O
O
HO
HO
O
O
NHAc
OH
10 60%
Br
O
OH
O
HO
HO
7
8
Br
NHAc
11 50%
OH
O
O
O
O
HO
HO
O
NHAc
OH
O
12 55%
O
O2N
9
starting material
OH
Cl
O
10
–
O
OH
Synlett 2009, No. 20, 3328–3332 © Thieme Stuttgart · New York

3330
R. Haddoub et al.
LETTER
tion mixture was then quenched with Et3N, evaporated under re-
duced pressure, and the residue was purified by flash
chromatography over silica gel (eluent: CH2Cl2–MeOH = 98:2) to
yield 1.03 g (3.13 mmol, 81%) of 2 as a brown oil.
1H NMR (400 MHz, CDCl3): d = 5.98 (d, 1 H, J1,2 = 7.2 Hz, H-1),
5.27 (m, 1 H, H-3), 4.93 (d, 1 H, J4,3 = J4,5 = 9.0 Hz, H-4), 4.18 (m,
3 H, H-2, H-6a, 6b), 3.61 (m, 1 H, H-5), 2.12, 2.11, 2.10, 2.09 (4 s,
12 H, 4 CH3).
O
OH
OH
O
O
R
OH
MW
HO
HO
HO
HO
R
O
NHAc
N
O
O
4
Scheme 2
Therefore, we turned our attention towards the use of un-
protected sugar oxazoline 4 (Scheme 2), reasoning that
under these conditions no glycosylation of the hydroxyl
groups would take place as found out with the serine ami-
no acid. De-O-acetylation of 2 was readily achieved upon
treatment with a catalytic amount of sodium in dry meth-
anol to give 4. Initial experiments were conducted using 4
and N-Fmoc glycine. Under optimized conditions [30
min, 80 °C, 200 W in acetonitrile–N,N-dimethylform-
amide (10:1)], the corresponding ester 5 was obtained in
63% isolated yield (Table 1, entry 1). A variety of carbox-
ylic acids were then screened to evaluate the scope of this
reaction (Table 1, entries 2–10). All compounds were
characterized by NMR spectroscopy after column chro-
matography purification, and a complete b stereoselectiv-
ity was obtained in all cases. Reaction with aliphatic acids
afforded the corresponding products 6 and 7 in 55% and
60% yield, respectively (entries 2 and 3). The reaction
2-Methyl-(1,2-dideoxy-a-D-glucopyrano)-[2,1-d]-2-oxazoline
(4)
To a solution of compound 2 in anhyd MeOH (2 mL) was added a
catalytic amount of sodium. The reaction was stirred at r.t. for 2 h,
then quenched with 1 M HCl. The solvent was removed under re-
duced pressure, and the crude product 4 was used without further
purification.
1H NMR (400 MHz, CD3OD): d = 5.99 (d, 1 H, J1,2 = 7.2 Hz, H-1),
4.01 (m, 1 H, H-2), 3.87 (t, 1 H, J2,3 = 3.6 Hz, H-3), 3.78–3.75 (dd,
1 H, J6a,6b = 12.4 Hz, J6a,5 = 2.4 Hz, H-6a), 3.65–3.61 (dd, 1 H,
J6b,5 = 6.8 Hz, H-6b), 3.54–3.50 (m, 1 H, H-4), 3.35–3.31(ddd, 1 H,
J5,6a = 2.4 Hz, J5,6b = 6.4 Hz, J5,4 = 9.2 Hz, H-5), 2.02 (s, 3 H, CH3).
Typical Procedure for the Synthesis of Glycosyl Ester
Oxazoline 4 (1 mmol) and carboxylic acid (1 mmol) were dispensed
into a microwave tube and dissolved in a 3 mL mixture of MeCN–
DMF (10:1). The tube was placed in a CEM Discover Microwave
Synthesizer. The reaction mixture was heated at 80 °C with a ramp-
ing time of 5 min then stirring for 28 min (200 W, 16.6 bar). The
crude product was concentrated in vacuo and purified by flash chro-
also proved compatible with carboxylic acids carrying matography over silica gel eluted with EtOAc–MeOH.
various functionalities, such as 2,6-dichlorophenylacetic
N-(9-Fluorenylmethoxycarbonyl)-L-serine (2-acetamido-2-
deoxy–b-D-glucopyranosyl) Ester (5)
Eluent (EtOAc–MeOH = 8:2); yield 63%.
acid (entry 4, 40% 8) and coumaric acid (entry 5, 45% 9).
In the case of aromatic carboxylic acids, benzoic acid, 4-
bromobenzoic acid and furoic acid (entries 6–8) reacted
1H NMR [400 MHz, (CD3)2SO]: d = 7.78–7.77 (m, 2 H, Har), 7.71
with 4 to afford the desired esters 10 (60%), 11 (50%), and
(m, 2 H, Har), 7.41 (m, 2 H, Har), 7.34–7.32 (m, 2 H, Har), 5.49 (m,
12 (55%), respectively. However, 2-chloro-4-nitrobenzo-
1 H, H-1), 4.13 (m, 1 H, CHFmoc), 4.26–4.24 (m, 2 H, CH2Fmoc),
ic acid (entry 9) failed to react with 4, and only starting
3.79–3.57 (m, 4 H, H-2, H-6a, CH2b), 3.48–3.45 (m, 1 H, H-6b),
materials were recovered. This result is probably due to
the low nucleophilicity of the carboxylate caused by the
electron-withdrawing 4-NO2 group. Finally, reaction with
4-benzoylbutyric acid (entry 10) only lead to decomposi-
tion products.
3.37–3.35 (m, 1 H, H-3), 3.17–3.16 (m, 2 H, H-4, H-5), 1.89 (s, 3
H, CH3).
13C NMR (100 MHz, CD3SO): d = 172.2, 169.1, 156.5 (2 C), 143.8
(2 C), 140.7 (2 C), 127.7 (2 C), 127.1 (2 C), 125.2 (2 C), 120.1 (2
C), 93.6, 78.1, 73.5, 69.9, 65.8, 60.5, 54.3, 46.6, 41.9, 22.9.
HRMS: m/z calcd for C25H28N2O9 [M + H]+: 501.1873; found:
501.1879.
In conclusion, we have described the preparation of novel
glycosyl esters of 2-acetamido-2-deoxy-b-D-glucopyra-
nose in fairly good yields under catalyst-free, microwave
conditions. This straightforward method proved compati-
ble with a range of diverse functionalized carboxylic ac-
ids, while avoiding the need for any coupling reagent and
overcoming the issue of anomeric selectivity. Notewor-
thy, the reaction can be performed directly from unpro-
tected oxazoline. Such method will be valuable for
attachment of sugar moiety onto biomolecules and the
synthesis of novel glycomimetics and glycopeptide ana-
logues.
2-Acetamido-2-deoxy-1-O-hexanoyl-b-D-glucopyranose (6)
Eluent (EtOAc–MeOH = 9:1); yield 55%.
1H NMR (400 MHz, CD3OD): d = 5.61–5.59 (d, 1 H, J1,2 = 8.8 Hz,
H-1), 3.87–3.82 (ta, 2 H, J = 9.6 Hz, H-2, H-6a), 3.71–3.67 (m, 1 H,
H-6b), 3.52–3.48 (t,1 H, J3,4 = J3,2 = 8.5 Hz, H-3), 3.38 (m, 2 H, H-
4, H-5), 2.36–2.31 (m, 2 H, CH2), 1.95 (s, 3 H, CH3), 1.64–1.57 (qu,
2 H, J = 7.2 Hz, CH2), 1.38–1.29 (m, 4 H, 2 CH2), 0.92 (t, 3 H,
J = 7.2 Hz, CH3).
13C NMR (100 MHz, CD3OD): d = 173.9, 173.6, 94.1, 78.8, 75.8,
71.6, 62.6, 56.3, 35.3, 32.3, 25.5, 23.5, 23.0, 14.4.
HRMS: m/z calcd for C14H25NO7 [M + Na]+: 342.1529; found:
342.1541.
Experimental Procedures and Spectroscopic Data
2-Methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-a-D-glucopyrano)-
[2,1-d]-2-oxazoline (2)20
1,2,3,4,6-Penta-O-acetyl-a-D-glucopyranose (1, 1.5 g, 3.85 mmol)
was refluxed for 16 h in dry CH2Cl2 (20 mL) under argon in the
presence of TMSOTf (850 mL, 4.62 mmol, 1.20 equiv). The reac-
2-Acetamido-2-deoxy-1-O-pentanoyl-b-D-glucopyranose (7)
Eluent (EtOAc–MeOH = 9:1); yield 60%.
1H NMR (400 MHz, CD3OD): d = 5.61–5.59 (d, 1 H, J1,2 = 8.8 Hz,
H-1), 3.87–3.82 (m, 2 H, H-2, H-6a), 3.71–3.67 (dd, 1 H,
J6b,6a = 12.4 Hz, J6b,5 = 3.0 Hz, H-6b), 3.52–3.48 (m,1 H, H-3), 3.38
Synlett 2009, No. 20, 3328–3332 © Thieme Stuttgart · New York

LETTER
Synthesis of 2-Acetamido-2-deoxy-b-D-glucopyranosyl Esters
3331
(m, 2 H, H-4, H-5), 2.25–2.23 (m, 2 H, CH2), 1.95 (s, 3 H, CH3),
1.64–1.57 (q, 2 H, J = 6.9 Hz, CH2), 1.34–1.29 (sx, 2 H, J = 6.9 Hz,
CH2), 0.93–0.90 (t, 3 H, J = 6.2 Hz, CH3).
13C NMR (100 MHz, CD3OD): d = 173.8, 173.6, 94.2, 78.9, 75.7,
71.6, 62.4, 56.2, 34.8, 27.9, 23.2, 22.9, 14.1.
HRMS: m/z calcd for C13H23NO7 [M + H]+: 306.1553; found:
306.1549.
2-Acetamido-2-deoxy-1-O-furoyl-b-D-glucopyranose (12)
Eluent (EtOAc–MeOH = 8:2). Yield: 55%.
1H NMR (400 MHz, CD3OD): d = 8.18 (dd, 1 H, J = 0.8–1.6 Hz,
Har), 7.60 (t, 1 H, J = 1.6 Hz, Har), 6.77 (dd, 1 H, J = 0.4–1.6 Hz,
Har), 5.70 (d, 1 H, J1,2 = 8.8 Hz, H-1), 3.99–3.94 (dd, 1 H, J2,1 = 8.8
Hz, J2,3 = 1.2 Hz, H-2), 3.88–3.85 (dd, 1 H, H-6a, J6a,6b = 12.0 Hz,
J6a,5 = 1.2 Hz, H-6a), 3.73–3.70 (m, 1 H, H-6b), 3.57–3.52 (m, 1 H,
H-3), 3.44–3.43 (m, 2 H, H-4, H-5), 1.92 (s, 3 H, CH3).
2-Acetamido-2-deoxy-1-O-(2,6-dichlorophenylacetyl)-b-D-glu-
copyranose (8)
13C NMR (100 MHz, CD3OD): d = 173.8, 162.9, 150.5, 145.8,
119.8, 110.6, 94.7, 78.9, 75.5, 71.6, 62.4, 56.1, 22.9.
Eluent (EtOAc–MeOH = 9:1); yield 40%.
HRMS: m/z calcd for C13H17NO8 [M + H]+: 316.1035; found:
316.1039.
1H NMR (400 MHz, CD3OD): d = 7.40–7.35 (t, 2 H, J = 9.5 Hz,
Har), 7.29–7.26 (m, 1 H, Har), 5.67–5.64 (d, 1 H, J1,2 = 11.0 Hz, H-
1), 4.05–4.03 (d, 2 H, J = 8.0 Hz, CH2), 3.88–3.80 (m, 2 H, H-2, H-
6a), 3.73–3.68 (m, 1 H, H-6b), 3.55–3.47 (m, 1 H, H-3), 3.40–3.38
(m, 2 H, H-4, H-5), 1.94 (s, 3 H, CH3).
13C NMR (100 MHz, CD3OD): d = 173.6, 169.7, 137.2 (2 C), 130.7,
129.3 (2 C), 129.1, 94.8, 79.1, 75.7, 71.6, 62.4, 56.2, 37.3, 23.0.
Acknowledgment
We are grateful to the European Union, RCUK, EPSRC and the
Royal Society (Wolfson Merit Award to SLF) for funding.
HRMS: m/z calcd for C16H19Cl2NO7 [M + Na]+: 430.0436; found:
430.0444.
References and Notes
(1) (a) Opdenakker, G.; Rudd, P. M.; Ponting, C. P.; Dwek,
R. A. FASEB J. 1993, 7, 1330. (b) Varki, A. Glycobiology
1993, 3, 97. (c) Dwek, R. A. Chem. Rev. 1996, 96, 683.
(2) Quideau, S.; Feldman, K. S. Chem. Rev. 1996, 96, 475.
(3) Smith, A. B. III.; Rivero, R. A.; Hale, K. J.; Vaccaro, H. A.
J. Am. Chem. Soc. 1991, 113, 2092.
(4) (a) Jacobsen, N. E.; Fairbrother, W. J.; Kensil, C. R.; Lim,
A.; Wheeler, D. A.; Powell, M. F. Carbohydr. Res. 1996,
280, 1. (b) Zhu, X.; Yu, B.; Hui, Y.; Higuchi, R.; Kusano, T.;
Miyamoto, T. Tetrahedron Lett. 2000, 41, 417.
(5) Graham, E. R. B.; Murphy, W. H.; Gottschalk, A. Biochim.
Biophys. Acta 1963, 74, 222.
2-Acetamido-1-O-(p-coumaryl)-2-deoxy-b-D-glucopyranose (9)
Eluent (EtOAc–MeOH = 8:2); yield 45%.
1H NMR (400 MHz, CD3OD): d = 7.71 (d, 1 H, J = 15.6 Hz, Hall),
7.49 (d, 2 H, J = 8.7 Hz, Har), 6.83 (d, 2 H, J = 8.5 Hz, Har), 6.31 (d,
1 H, J = 15.6 Hz, Hall), 5.68 (d, 1 H, J1,2 = 8.8 Hz, H-1), 4.00–3.95
(dd, 1 H, J2,1 = 8.8 Hz, J2,3 = 10.0 Hz, H-2), 3.91–3.87 (dd, 1 H,
J6a,6b = 12.4 Hz, J6a,5 = 1.6 Hz, H-6a), 3.75–3.71 (dd, 1 H,
J6b,6a = 12.0 Hz, J6b,5 = 4.8 Hz, H-6b), 3.58–3.54 (m, 1 H, H-3),
3.45–3.43 (m, 2 H, H-4, H-5), 1.96 (s, 3 H, CH3).
13C NMR (100 MHz, CD3OD): d = 173.9, 167.5, 161.7, 148.5,
131.5 (2 C), 126.9, 116.9 (2 C), 114.1, 94.5, 78.9, 75.8, 71.5, 62.5,
56.3, 22.9.
(6) Ecker, M.; Deutzmann, R.; Lehle, L.; Mrsa, V.; Tanner, W.
J. Biol. Chem. 2006, 281, 11523.
HRMS: m/z calcd for C17H21NO8 [M + Na]+: 390.1165; found:
390.1147.
(7) Jones, A. E.; Wilson, H. K.; Meath, P.; Meng, X.; Holt,
D. W.; Johnston, A.; Oellerich, M.; Armstrong, V. W.;
Stachulski, A. V. Tetrahedron Lett. 2009, 50, 4973.
(8) Berry, N. G.; Iddon, L.; Iqbal, M.; Meng, X.; Jayapal, P.;
Johnson, C. H.; Nicholson, J. K.; Lindon, J. C.; Harding,
J. R.; Wilson, I. D.; Stachulski, A. V. Org. Biomol. Chem.
2009, 7, 2525.
2-acetamido-1-O-benzoyl-2-deoxy-b-D-glucopyranose (10)
Eluent (EtOAc–MeOH = 9:1); yield 60%.
1H NMR (400 MHz, CD3OD): d = 8.05–8.03 (d, 2 H, J = 8.0 Hz,
Har), 7.63 (t, 1 H, J = 7.2 Hz, Har), 7.50–7.47 (t, 2 H, J = 7.2 Hz,
Har), 5.76 (d, 1 H, J1,2 = 8.8 Hz, H-1), 4.07 (t, 1 H, J2,1 = 8.8 Hz, H-
2), 3.89–3.86 (dd, 1 H, J6a,6b = 12.0 Hz, J6a,5 < 1 Hz, H-6a), 3.70 (dd,
1 H, J6b,6a = 12.0 Hz, J6b,5< 1.0 Hz, H-6b), 3.60–3.55 (m, 1 H, H-3),
3.46 (m, 2 H, H-4, H-5), 1.90 (s, 3 H, CH3).
13C NMR (100 MHz, CD3OD): d = 173.3, 166.0, 134.4, 130.5,
130.0 (2 C), 129.3 (2 C), 94.6, 78.6, 75.1, 71.1, 62.0, 55.6, 22.7.
HRMS: m/z calcd for C15H19NO7 [M + Na]+: 348.1059; found:
348.1077.
(9) Kornhauser, A.; Keglevic, D. Carbohydr. Res. 1969, 11,
407.
(10) Pfander, H.; Wittwer, F. Helv. Chim. Acta 1979, 62, 1944.
(11) Smith, A. B. III.; Hale, K. J.; Rivero, R. A. Tetrahedron Lett.
1986, 27, 5813.
(12) Kim, Y.-J.; Wang, P.; Navarro-Villalobos, M.; Rohde, B. D.;
Berry, D.; Gin, D. Y. J. Am. Chem. Soc. 2006, 128, 11906.
(13) Crich, D.; Cai, F. Org. Lett. 2007, 9, 1613.
(14) Fernandez, C.; Nieto, O.; Rivas, E.; Montenegro, G.;
Fontenla, J. A.; Fernandez-Mayoralas, A. Carbohydr. Res.
2000, 327, 353.
(15) (a) Li, X.; Danishefsky, S. J. J. Am. Chem. Soc. 2008, 130,
4556. (b) Fraser-Reid, B.; Merritt, J. R.; Handlon, A. L.;
Andrews, C. W. Pure Appl. Chem. 1993, 65, 779.
(c) Paulsen, H.; Schleyer, A.; Mathieux, N.; Meldal, M.;
Bock, K. J. Chem. Soc., Perkin Trans. 1 1997, 281.
(d) Salvador, L. A.; Elofsson, M.; Kihlberg, J. Tetrahedron
1995, 51, 5643.
(16) Bols, M.; Hansen, H. C. Acta Chem. Scand. 1993, 47, 818.
(17) Binkley, R. C.; Ziepfel, J. C.; Himmeldirk, K. B. Carbohydr.
Res. 2009, 344, 237.
2-Acetamido-1-O-(4-bromobenzoyl)-2-deoxy-b-D-glucopyra-
nose (11)
Eluent (EtOAc–MeOH = 9:1); yield 50%.
1H NMR (400 MHz, CD3OD): d = 7.87–7.82 (d, 2 H, J = 8.8 Hz,
Har), 7.61–7.55 (d, 2 H, J = 8.8 Hz, Har), 5.70 (d, 1 H, J1,2 = 8.8 Hz,
H-1), 4.00–3.95 (m, 1 H, H-2), 3.83–3.80 (m, 1 H, H-6a), 3.75–3.71
(m, 1 H, H-6b), 3.58–3.54 (m, 1 H, H-3), 3.43–3.40 (da, 2 H, J = 6.4
Hz, H-4, H-5), 1.96 (s, 3 H, CH3).
13C NMR (100 MHz, CD3OD): d = 173.6, 167.0, 132.6 (2 C), 132.4
(2 C), 129.8, 127.2, 95.3, 79.0, 75.4, 71.6, 62.4, 56.0, 22.9.
(18) (a) Bejugam, M.; Flitsch, S. L. Org. Lett. 2004, 6, 4001.
(b) Laurent, N.; Voglmeir, J.; Wright, A.; Blackburn, J. M.;
Pham, N. T.; Wong, S. C. C.; Gaskell, S. J.; Flitsch, S. L.
HRMS: m/z calcd for C15H18BrNO7 [M + H]+: 404.0345; found:
404.0352.
Synlett 2009, No. 20, 3328–3332 © Thieme Stuttgart · New York

3332
R. Haddoub et al.
LETTER
ChemBioChem 2008, 9, 883. (c) Laurent, N.; Voglmeir, J.;
Flitsch, S. L. Chem. Commun. 2008, 4400. (d) Laurent, N.;
Haddoub, R.; Voglmeir, J.; Wong, S. C. C.; Gaskell, S. J.;
Flitsch, S. L. ChemBioChem 2008, 9, 2592.
(20) Nakabayashi, S.; Warren, C. D.; Jeanloz, R. W. Carbohydr.
Res. 1986, 150, C7.
(21) (a) In particular, the CH2 of the serine was found at d = 62.4
ppm in the 13C NMR spectrum of 3b, as compared to
d = 68.8 ppm for compound 3a (see ref. 21b). Further
confirmation of the structure was obtained by acetylation of
the free hydroxyl of 3b in Ac2O–pyridine and by its
unreactivity towards amines in the presence of PyBOP and
DIPEA. (b) Carvalho, I.; Scheuerl, S. L.; Kartha, K. P. R.;
Field, R. A. Carbohydr. Res. 2003, 338, 1039; for NMR data
of 3a.
(19) (a) Kiso, M.; Anderson, L. Carbonhydr. Res. 1979, 72, C12.
(b) Hollosi, M.; Kollat, E.; Laczko, I.; Medzihradszky, K. F.;
Thurin, J.; Otvos, L. Tetrahedron Lett. 1991, 32, 1531.
(c) Arsequell, G.; Krippner, L.; Dwek, R. A.; Wong, S. Y. C.
J. Chem. Soc., Chem. Commun. 1994, 2383. (d) Wittmann,
V.; Lennartz, D. Eur. J. Org. Chem. 2002, 8, 1363.
(e) Crasto, C. F.; Jones, G. B. Tetrahedron Lett. 2004, 45,
4891.
Synlett 2009, No. 20, 3328–3332 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.