Azidonitration of di-O-acetyl-L-fucal: X-Ray crystal structures of intermediate azidodeoxysugars and of the bacterial aminosugar N-acetyl-L-fucosamine

Article abstract of DOI:10.1080/07328303.2012.658125

The azidonitration of di-O-acetyl-L-fucal has previously been shown to be an efficient route to the bacterial aminosugar N-acetyl-L-fucosamine. Upon repeating this sequence, with updated versions of the glycal formation and amide installation steps, we have obtained X-ray crystal structures of several of the addition products, which are now reported along with the solid-state structure of N-acetyl-L-fucosamine itself. Copyright Taylor & Francis Group, LLC.

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Azidonitration of Di-O-acetyl-L-fucal: X-
Ray Crystal Structures of Intermediate
Azidodeoxysugars and of the Bacterial
Aminosugar N-Acetyl-L-fucosamine
Abdul-Basit Alhassan a , David C. McCutcheon a , Matthias Zeller a
Peter Norris a
a Department of Chemistry , Youngstown State University ,
Youngstown , OH , 44555 , USA
&
Published online: 02 Jul 2012.
To cite this article: Abdul-Basit Alhassan , David C. McCutcheon , Matthias Zeller & Peter
Norris (2012) Azidonitration of Di-O-acetyl-L-fucal: X-Ray Crystal Structures of Intermediate
Azidodeoxysugars and of the Bacterial Aminosugar N-Acetyl-L-fucosamine, Journal of Carbohydrate
Chemistry, 31:4-6, 371-383, DOI: 10.1080/07328303.2012.658125
To link to this article: http://dx.doi.org/10.1080/07328303.2012.658125
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Journal of Carbohydrate Chemistry, 31:371–383, 2012
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2012.658125
Azidonitration of Di-O-acetyl-
L-fucal: X-Ray Crystal
Structures of Intermediate
Azidodeoxysugars and of the
Bacterial Aminosugar
N-Acetyl-L-fucosamine
Abdul-Basit Alhassan, David C. McCutcheon, Matthias Zeller,
and Peter Norris
Department of Chemistry, Youngstown State University, Youngstown, OH 44555, USA
The azidonitration of di-O-acetyl-L-fucal has previously been shown to be an effi-
cient route to the bacterial aminosugar N-acetyl-L-fucosamine. Upon repeating this se-
quence, with updated versions of the glycal formation and amide installation steps, we
have obtained X-ray crystal structures of several of the addition products, which are
now reported along with the solid-state structure of N-acetyl-L-fucosamine itself.
Keywords Azidonitration; L-Fucal; N-Acetyl-L-fucosamine; Aminosugar; X-ray
structure
INTRODUCTION
Azidonitration of glycals, as first reported by Lemieux,[1] has long been a use-
ful and reliable method for the construction of 2-azido-2-deoxysugars. An ex-
cellent example of the preparative-scale application of this chemistry is the
synthesis of N-acetyl-L-fucosamine (N-acetyl-2-amino-2,6-dideoxy-L-galactose)
1 by Horton and Anisuzzaman, which still serves as the most reliable synthetic
approach to this compound.[2] More recently, aminosugar 1 has been reported
Received November 6, 2011; accepted January 12, 2012.
Address correspondence to Matthias Zeller and Peter Norris, Department of Chem-
istry, Youngstown State University, 1 University Plaza, Youngstown, OH 44555, USA.
E-mail: mzeller@ysu.edu; pnorris@ysu.edu
371

A.-B. Alhassan et al.
372
to be an important component of several bacterial polysaccharides, notably in
strains of Staphylococcus aureus and Pseudomonas aeruginosa, and studies
have described its detailed biosynthesis and incorporation into capsules.[3] Ac-
cordingly, the enzymatic construction of aminosugar 1 now presents several
viable protein targets for potential interaction with synthetic glycomimetics,
especially considering that this aminosugar is not utilized in human biochem-
istry. With this long-term goal in mind, we have repeated the azidonitration
chemistry on di-O-acetyl-L-fucal, with updated methods applied at two of the
steps, and obtained crystal structures of two of the intermediate azide prod-
ucts, as well as the solid-state structure of N-acetyl-L-fucosamine itself.
RESULTS AND DISCUSSION
The traditional route to 3,4-di-O-acetyl-L-fucal (5) requires, firstly, the acety-
lation of L-fucose (2) to produce the tetra-O-acetate 3 (Scheme 1). Bromination
with HBr in acetic acid then affords the α-bromide 4, which is subsequently
treated with, for example, Zn dust to generate the glycal in good yield.[4] Al-
ternative methods for elimination from glycosyl bromides have been developed
recently, notably the use of catalytic Cp2TiCl2 by Skrydstrup and co-workers.[5]
In our hands, application of this latter method to glycosyl bromide 4 on an 11.7-
mmol scale provided 3,4-di-O-acetyl-L-fucal (5) in 88% isolated yield.
Scheme 1: Synthesis of 5. Reagents and conditions: (i) Ac2O, pyridine, 0◦C, 12 h; (ii) HBr,
AcOH, 25◦C, 3 h; (iii) Cp2TiCl2, Mn, TMSCl, THF, 25◦C, 12 h.
Azidonitration on fucal 5, as described previously by Horton[2] and also
by Thiem,[6] on a 10-mmol scale resulted in the isolation of a mixture of
mostly the anomeric nitrates 6 in 71% crude yield, which was then used
without further purification for the subsequent acetolysis. After reacting this
crude mixture with acetic acid, Ac2O, and NaOAc at reflux for 5 h, the 1,3,4-
tri-O-acetyl-2-azidodeoxy-α/β-L-fucoses (7) were isolated in 52.6% yield after
column chromatography, along with a mixture of 1-N-acetyl-3,4-di-O-acetyl-2-
azidodexy-α/β-L-fucopyranosylamines (8), isolated in 40% yield. In both cases,
the alpha anomers of 7 and 8 could be isolated in crystalline form from boiling
ethanol solution to provide material suitable for single-crystal X-ray diffrac-
tion. Glycosyl amide 8α was previously reported by Lehman and co-workers as
a product of the reaction of nitrates 6α/β with concentrated NH4OH followed
by standard acetylation,[7] and a related glycosyl amide was also formed in

Azidonitration of Di-O-acetyl-L-fucal
373
Figure 1: ORTEP plot of 7α (50% probability of the thermal ellipsoids) (color figure available
online).
the original Lemieux work during the addition reaction of 3,4-di-O-acetyl-D-
galactal using CAN and NaN3.[1] The amide might be formed by oxidation of
an intermediate glycosyl radical to the carbonium ion, followed by trapping of
the carbonium ion by solvent (acetonitrile) and then hydrolysis.[1] The X-ray
structures of both 7α (Fig. 1, Tables 1 and 2)[8] and the monohydrate of 8α
(Fig. 2, Table 1)[9] clearly establish the alpha anomeric configuration of both
compounds. Interestingly, the orientation of the glycosyl amide group in 8α is
revealed to have the C-1 and amide NH protons aligned in an anti relation-
ship, which is mirrored in CDCl3 solution where the 1H NMR spectrum shows
the H-1–N-H coupling constant to be 9.89 Hz. An overlay of the two structures
(7α and 8α) indicates an almost perfect match-fitting for C-1 to C-6 with a root
˚
mean square (rms) deviation of only 0.0224A.
In the earlier synthesis of N-acetyl-L-fucosamine by Horton and Anisuz-
zaman, azides 7 were reduced with H2 and the resultant amines acylated
in the typical manner.[2] In the current work we employed Staudinger-type
chemistry, in which the azide is treated with a phosphine and the result-
ing phosphinimine ylide acylated, and found our own modification using

k
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C
P
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l
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k
h
k
S
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R
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T
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374

Azidonitration of Di-O-acetyl-L-fucal
375
Table 2: Hydrogen-bond parameters of 8α·H2O
D—H···A
D—H (Å)
H···A (Å)
D···A (Å)
D—H···A (◦)
N4 H4A···O8i
O8 H8D···O3ii
O8 H8E···O5
O8 H8F···O8i
0.82 (3)
0.839 (18)
0.84 (2)
0.82 (2)
2.06 (3)
1.904 (18)
2.00 (2)
2.08 (3)
2.8845 (19)
2.7347 (18)
2.838 (3)
177 (2)
170 (3)
173 (5)
155 (6)
2.846 (2)
Symmetry code(s): (i) -x + 1, y, -z + 2; (ii) -x + 1, y – 1, -z + 2.
Figure 2: ORTEP plots of 8α·H2O (50% probability of the thermal ellipsoids). Left: one
molecule with the atom naming scheme and the solvate water molecule and disorder
omitted for clarity. Right: Partial packing view highlighting the disorder induced by the
symmetry-incompatible hydrogen bonding interactions of the solvate water molecules. A
twofold symmetry axis passes between the two symmetry-equivalent water molecules.
Highlighted in orange is the second orientation of the disordered sections realized for 50% of
the structure (see Experimental section for details of the disorder). Dashed lines represent
hydrogen bonds. Parts of molecules and H atoms not involved in displayed hydrogen bonds
are omitted for clarity (color figure available online).
Scheme 2: Synthesis of 1. Reagents and conditions: (i) CAN, NaN3, CH3CN, –15◦C, 12 h; (ii)
NaOAc, AcOH, Ac2O, reflux, 5 h; (iii) DPPE, AcCl, THF, 25◦C, 3 h; (iv) NaOCH3, CH3OH, rt, 3 h.

A.-B. Alhassan et al.
376
Figure 3: ORTEP plot of 1 (50% probability of the thermal ellipsoids). Left: One individual
molecule. Right: Next neighbor, hydrogen bonding atoms shown (color figure available
online).
bis(diphenylphosphino)ethane (DPPE) to be applicable here.[10] The byprod-
uct formed here is a very polar bis(phosphine)bisoxide, which aids in separa-
tion from other materials (Scheme 2). Thus, treating azidodeoxysugar 7α with
0.65 equivalents of DPPE, in the presence of 2.0 equivalents of acetyl chloride,
afforded 1,3,4-tri-O-acetyl-2-N-acetyl-2-deoxy-α-L-fucosamine (9) in 82% yield.
The structure of 9 was confirmed from NMR spectroscopy and mass spectral
data, with its physical characteristics being consistent with those observed
previously.[2]
With 9 in hand, traditional deacetylation with NaOMe in MeOH was
uneventful and provided the parent N-acetylated aminosugar, N-acetyl-α-L-
fucosamine (1), upon crystallization from hot ethanol. The structure of 1 has
now been confirmed independently through X-ray crystallography (Fig. 3, Ta-
ble 1).[11] After removal of the acetyl protecting groups, molecules of 1 are able
to interact with each other through an extensive network of strong intermolec-
ular N H···O and O H···O hydrogen bonding interactions (Table 3, Fig. 4).
All hydroxyl O H groups and the amide N H functionality act as hydrogen
Table 3: Hydrogen-bond parameters of 1
D
H···A
D
H (Å)
H···A (Å)
D···A (Å)
D
H···A (◦)
N1 H1A···O3i
O2 H2A···O5ii
O3 H3A···O4i
O3 H3A···O3i
O4 H4A···O2iii
0.85 (2)
0.92 (2)
0.75 (3)
0.75 (3)
0.84 (2)
2.16 (2)
1.74 (2)
2.28 (3)
2.31 (3)
2.05 (3)
2.9356 (15)
2.6531 (14)
2.8892 (14)
2.9187 (6)
2.8150 (15)
151 (2)
178 (2)
139 (3)
139 (2)
151 (2)
Symmetry code(s): (i) -x + 1, y – 1/2, -z; (ii) -x + 1, y – 1/2, -z + 1; (iii) x, y + 1, z.

Azidonitration of Di-O-acetyl-L-fucal
377
Figure 4: Intermolecular H-bonding network and packing interactions exhibited by
aminosugar 1 viewed along the direction of (a) the a-axis perpendicular to the hydrogen
bonded layers of molecules, and (b) and (c) along the b- and c-axis cutting through those
layers. Tightly hydrogen bonded double strands of molecules can be seen in (a) that stretch
parallel to the b-axis with only a few hydrogen bonds connecting parallel strands (color
figure available online).
bonding donors, and all oxygen atoms, with the notable exception of the pyra-
nose ring O atom O1, function as acceptors for hydrogen bonds. One of the
hydroxyl functionalities, that of O3, forms a bifurcated hydrogen bond, in-
teracting strongly with both O3 and O4 of neighboring molecules (graph set
motif R21(5)). O3 also acts as the acceptor of a hydrogen bond originating
from a neighboring amido group (graph set motif R12(7)). Originating from
this cluster of H-bonds around O3 and O4 are chains of O H···O bonds in-
volving the hydroxyl group of O2, acting both as acceptor and donor, and the
acetyl oxygen atom O5, which functions as a termination point of the chains of
O H···O hydrogen bonds. In combination of all interactions, an intricate hy-
drogen bonding network is formed that organizes the molecules of 1 into tightly
hydrogen bonded layers perpendicular to the direction of the unit cell a-axis.

A.-B. Alhassan et al.
378
Within these one-molecule-thick sheets, molecules are arranged parallel and
antiparallel to each other, with the two methyl groups of each molecule (the
acetyl amide and the fucosamine methyl groups) forming the top and bottom
boundary of the hydrogen bonded layers. No hydrogen bonds are established
in the direction of these long axes of the molecules between parallel layers.
Within the 2-D sheets, additional double strands of molecules can be made out
that stretch along the b-axis direction. Within these strands, molecules are
connected through multiple hydrogen bonds each as described above, while
molecules of parallel strands are connected only through one hydrogen bond,
between the hydroxyl group of O2 and the acetyl oxygen atom O5.
The orientation of the NHAc moiety relative to the fucopyranosyl ring in
the solid-state structure of 1 (Fig. 3) shows H2 and the NH group to be aligned
1
at an angle of 148◦. In the H NMR spectrum of this material, collected in
d6-DMSO, the observed H2–NH coupling of 8.79 Hz indicates that a similar
alignment is also occurring in solution.
In conclusion, the structure of the bacterial aminosugar N-acetyl-L-
fucosamine (1) has been obtained through single-crystal X-ray diffraction,
along with two of the intermediate azidodeoxysugars (7α and 8α·H2O) formed
along the azidonitration route to 1 developed previously by Horton and Anisuz-
zaman.[2] The detailed structure of 1 may now aid in the design and synthesis
of related glycomimetics that are capable of interacting with the proteins re-
sponsible for its construction in bacteria.
EXPERIMENTAL
General Methods
Reagents and solvents were used as received and reactions were carried
out in oven-dried glassware under nitrogen atmosphere unless noted. An-
alytical TLC was performed on Whatman aluminum-backed plates coated
˚
with 60 A silica gel, and spots were detected by treating the plate with 5%
H2SO4 in 95% ethanol, p-anisaldehyde in ethanol, or phosphomolybdic acid in
aqueous ethanol and then heating the plate. Products were purified by flash
˚
column chromatography using 60 A silica gel (230–400 mesh) and/or recrystal-
lization from the indicated solvent(s). H and 13C NMR spectra were collected
1
at 400 MHz and 100 MHz, respectively, using Varian Gemini 2000 or Bruker
Avance 400 MHz spectrometers in CDCl3 or d6-DMSO as solvents. Chemical
shifts are reported relative to the added tetramethylsilane standard. Low-
resolution mass spectra were collected on a Bruker Esquire HP 1100 mass
spectrometer, and X-ray diffraction data were obtained using a Bruker AXS
SMART APEX CCD diffractometer at 100(2) K using monochromatic Mo Kα
radiation with omega scan technique using the SMART software.[12] The unit
cells were refined and the data integrated using SAINT+.[13] The structures

Azidonitration of Di-O-acetyl-L-fucal
379
were solved by direct methods and refined by full-matrix least squares against
F2 with all reflections using SHELXTL.[14] All nonhydrogen atoms were re-
fined anisotropically. Methyl H atoms were placed in geometrically idealized
positions allowing the initial torsion angle to be determined by a difference
˚
Fourier analysis [C-H = 0.96 A and Uiso(H) = 1.5eq(C)]. All other hydrogen
atoms were located in difference density Fourier maps and their positions
were freely refined. O-H distances in the water molecule in the structure of
˚
8α·H2O were restrained to be 0.84(2)A. Uiso(H) were set to 1.5eq(O) for hydroxyl
and water H atoms, and to 1.2eq(C/N) for all others. Friedel equivalents were
merged prior to refinement and the absolute structure of the compounds was
assigned based on the unchanged configuration of carbon atoms also present
in the starting material.
Disorder is observed in the structure of 8α·H2O. Hydrogen bonding of the
solvate water molecule with its symmetry equivalent across a twofold axis
leads to disorder of one of the water hydrogen atoms (in a 1:1 ratio), with the
hydrogen atom forming a hydrogen bond between the two water molecules in
one of the alternative positions and forming a hydrogen bond with O5 of one
of the acetyl groups of the organic entity in its other position. This in turn in-
duces disorder of the acetyl group in a 1:1 ratio. The disordered acetyl groups
were restrained to be flat, and the overlapping carbon atoms C9 and C9b, and
C10 and C10b were each constrained to have identical ADPs.
Synthesis of 3,4-Di-O-acetyl-L-fucal from L-Fucose
1,2,3,4-Tetra-O-acetyl-α/β-L-fucoses (3)
Formed from L-fucose (2.5 g, 15.2 mmol), Ac2O (7.5 mL), and pyridine
(25 mL) to yield the known α- and β-tetra-O-acetyl-L-fucoses (3) as a color-
less syrup (α:β ratio = 14:1, 4.89 g, 96%). 1H NMR for 3α (CDCl3): δ = 1.14 (d,
3H, H-6, J = 6.22 Hz), 1.99 (s, 3H, COCH3), 2.00 (s, 3H, COCH3), 2.13 (s, 3H,
COCH3), 2.17 (s 3H, COCH3), 4.26 (q, 1H, H-5, J = 6.22 Hz), 5.04 (dd, 1H, H-4,
J = 3.66, 10.62 Hz), 5.24–5.30 (m, overlapping, 2H, H-2, H-3), 6.32 (d, 1H, H-1,
J = 2.93 Hz). MS (ESI): m/z calculated: 332.11; m/z found: 355.1 (M+Na).
The data is consistent with that reported previously for 3.[15]
2,3,4-Tri-O-acetyl-α-L-fucosyl bromide (4)
Prepared from a mixture of α/β-tetraacetates 3 (4.6 g, 13.86 mmol) and 30%
HBr in acetic acid (20.0 mL) to give the glycosyl bromide 4 as a light brown
1
syrup (4.18 g, 85.5%). H NMR (CDCl3): δ = 1.20 (d, 3H, H-6, J = 6.59 Hz),
2.00 (s, 3H, COCH3), 2.10 (s, 3H, COCH3), 2.16 (s, 3H, COCH3), 4.39 (q, 1H,
H-5, J = 6.59 Hz), 5.01 (dd, 1H, H-2, J = 4.03, 10.62 Hz), 5.35 (d, 1H, H-4, J =
3.30 Hz), 5.39 (dd, 1H, H-3, J = 3.30, 10.62 Hz), 6.68 (d, 1H, H-1, J = 4.03).
13C NMR (CDCl3): δ = 16.6, 21.6, 21.7, 21.8, 68.8, 69.4, 70.9, 71.0, 90.5, 170.6,

A.-B. Alhassan et al.
380
170.9, 171.1. The spectral properties match those reported earlier for bromide
4.[16]
3,4-Di-O-acetyl-L-fucal (5)
According to the method of Skrydstrup and co-workers,[5] 2,3,4-tri-O-
acetyl-α-L-fucosyl bromide (4, 4.13 g, 11.7 mmol), Cp2TiCl2 (1.90 g, 7.6 mmol),
Mn powder (1.24 g, 22.5 mmol), and TMSCl (0.4 mL) in dry THF (50 mL) gave
1
the known 3,4-di-O-acetyl-L-fucal (5) as a pale yellow syrup (2.2 g, 88%). H
NMR (CDCl3): δ = 1.27 (d, 3H, H-6, J = 6.59 Hz), 2.02 (s, 3H, COCH3), 2.16
(s, 3H, COCH3), 4.21 (q, 1H, H-5, J = 6.59 Hz), 4.64 (ddd, 1H, H-3, J = 1.83,
6.22, 9.89 Hz), 5.28 (m, 1H, H-2), 5.57 (m, 1H, H-4), 6.46 (dd, 1H, H-1, J =
1.83, 6.22 Hz). 13C NMR (CDCl3): δ = 17.8, 22.0, 22.2, 66.2, 67.4, 72.7, 99.4,
147.1, 171.4, 171.7. The collected data are consistent with that of a previously
reported sample of 5.[17]
Azidonitration of 3,4-Di-O-acetyl-L-fucal
2-Azido-1-O-nitro-3,4-di-O-acetyl-α/β-L-fucose (6)
Using Thiem’s approach,[6] sodium azide (1.6 g, 24.6 mmol), ceric ammo-
nium nitrate (CAN, 18.25 g, 33.3 mmol), and 3,4-di-O-acetyl-L-fucal (5, 2.21 g,
10.3 mmol) in anhydrous acetonitrile (100 mL) gave a yellow solid (α:β ratio =
3:1, 2.45 g, 71%) identified mostly as nitrates 6 from NMR spectra. For 6α: 1H
NMR (CDCl3): δ = 1.18 (d, 3H, H-6, J = 6.48 Hz), 2.07 (s, 3H, COCH3), 2.19
(s, 3H, COCH3), 4.10 (dd, 1H, H-2, J = 4.18, 11.30 Hz), 4.31 (q, 1H, H-5, J =
6.44 Hz), 5.26 (dd, 1H, H-3, J = 3.30, 11.46 Hz), 5.35 (dd, 1H, H-4, J = 1.13,
3.23 Hz), 6.32 (d, 1H, H-1 J = 4.12 Hz). 13C NMR (CDCl3): δ = 15.7, 20.4(2),
1
20.44, 55.7, 67.9, 68.8, 69.6, 97.3, 169.4, 170.0. For 6β: H NMR (CDCl3): δ =
1.24 (d, 3H, H-6, J = 6.44 Hz), 2.06 (s, 3H, COCH3), 2.19 (s, 3H, COCH3), 3.56
(dd, 1H, H-2, J = 8.94, 10.62), 3.87 (dq, 1H, H-5, J = 6.41, 0.95 Hz), 4.60 (d,
1H, H-1, J = 8.88 Hz), 4.85 (dd, 1H, H-3, J = 3.32, 10.64 Hz), 5.22 (dd, 1H, H-4
J = 0.80, 3.28 Hz). 13C NMR (CDCl3): δ = 15.9, 20.5(2), 60.3, 69.1, 71.2, 71.8,
89.1, 169.6, 170.2.
1,3,4-tri-O-acetyl-2-azidodeoxy-α/β-L-fucose (7) and
1,3,4-tri-O-acetyl-2-azidodeoxy-α-L- fucopyranosylamine (8α)
The crude mixture from the previous experiment (2.4 g, 7.18 mmol) was
dissolved in acetic acid (70 mL), NaOAc (4.3 g, 51.9 mmol) and Ac2O (3 mL)
were added, and the solution was refluxed for 5 h and then poured into ice
water. The mixture was extracted with CH2Cl2 (4 × 30 mL) and the combined
organic layers were washed with saturated NaHCO3 (3 × 25 mL) and once
with saturated NaCl solution (25 mL). The organic layer was dried (MgSO4),

Azidonitration of Di-O-acetyl-L-fucal
381
filtered, and reduced in vacuum, and the residue was purified by flash chro-
matography (3:1 pet. ether/EtOAc) to afford 1.19 g (52.6%) of an α/β mixture
of azidoacetates 7 and 0.9 g (40%) of azidoamide 8. The α-anomers of 7 and 8
were crystallized out by vapor diffusion and from hot ethanol, respectively.
For 7α/β: 1H NMR (CDCl3): δ = 1.13 (d, 3H, H-6α, J = 6.59 Hz), 1.20 (d, 3H,
H-6β, J = 6.59 Hz), 2.05 (s, 3H, COCH3β), 2.06 (s, 3H, COCH3β), 2.15 (s, 3H,
COCH3α), 2.17 (s, 3H, COCH3α), 2.18 (s, 3H, COCH3β), 2.19 (s, 3H, COCH3β),
3.81 (dd, 1H, H-2β, J = 8.79, 10.98 Hz), 3.89 (dd, 1H, H-2α, J = 3.66, 11.72 Hz),
3.90 (q, 1H, H-5β, J = 6.59 Hz), 4.19 (q, 1H, H-5α, J = 6.22 Hz), 4.87 (dd, 1H,
H-3β, J = 3.30, 10.98 Hz), 5.22 (d, 1H, H-4β, J = 4.03 Hz), 5.28–5.32 (m, over-
lapping, 2H, H-3α, H-4α), 5.51 (d, 1H, H-1β, J = 8.79 Hz), 6.27 (d, 1H, H-1α,
J = 3.66 Hz). 13C NMR (α anomer) (CDCl3): δ = 17.2, 21.9(2), 22.3, 57.9, 68.4,
70.3, 71.2, 91.8, 170.0, 170.9, 171.4. 13C NMR (β anomer) (CDCl3): δ = 17.2,
21.9(2), 22.2, 60.8, 70.4, 71.4, 72.8, 94.0, 169.8, 170.7, 171.3. These spectral
characteristics match those reported previously for a mixture of 7α/β;[6] the
structure of 7α has now been confirmed independently by X-ray diffraction.
1
For 8α: H NMR (CDCl3): δ = 1.13 (d, 3H, H-6, J = 6.44 Hz), 2.10 (s, 3H,
COCH3), 2.11 (s, 3H, COCH3), 2.20 (s, 3H, COCH3), 4.01 (q, 1H, H-5, J =
6.39 Hz), 4.16 (dd, 1H, H-2, J = 5.53, 11.08 Hz), 5.22 (d, 1H, H-4, J = 2.68 Hz),
5.27 (dd, 1H, H-3, J = 3.34, 11.10 Hz), 5.86 (dd, 1H, H-1, J = 5.58, 8.06 Hz),
7.38 (d, 1H, H-N, J = 8.08 Hz). 13C NMR (CDCl3): δ = 16.2, 20.7, 20.8, 23.2,
56.7, 65.4, 70.1, 70.2, 75.4, 170.7, 170.8, 171.6. These spectra are consistent
with the structure of 8α proposed previously by Lehman[7] and confirmed here
independently by X-ray diffraction.
Synthesis of N-Acetyl-L-fucosamine
1,2,3,4-tetra-O-acetyl-α-L-fucosamine (9)
This compound was prepared by our previously reported method us-
ing Staudinger chemistry with DPPE as the phosphine.[10] 1,3,4-Tri-O-
acetyl-2-azidodeoxy-α-L-fucose (7α) (0.32 g, 1.00 mmol) and acetyl chloride
(0.14 mL, 2.0 mmol) were dissolved in dry THF (7.3 mL) at rt, and then
bis(diphenylphosphino)ethane (DPPE, 0.26 g, 0.65 mmol) dissolved in dry THF
(3 mL) was added dropwise. After 3 h at rt, saturated NaHCO3 solution (5 mL)
was added and the mixture was stirred for an additional 2 h at rt. After
evaporation of the organic solvent, the aqueous solution was extracted with
CH2Cl2 (3 × 10 mL) and the combined organics were washed with H2O (2 ×
10 mL), dried (MgSO4), and concentrated under reduced pressure. The residue
was purified by flash column chromatography (7:1, EtOAc/hexanes) to obtain
the previously reported 1,2,3,4-tetra-O-acetyl-α-L-fucosamine (9) as a colorless
syrup (0.27 g, 82 %), which could be crystallized from hot ethanol.[2,7] 1H NMR
(CDCl3) for 9: δ = 1.15 (d, 3H, H-6, J = 6.49 Hz), 1.95 (s, 3H, COCH3), 2.01 (s,

A.-B. Alhassan et al.
382
3H, COCH3), 2.17 (s, 3H, COCH3), 2.19 (s, 3H, COCH3), 4.22 (q, 1H, H-5, J =
6.44 Hz), 4.64 (ddd, 1H, H-2, J = 3.56, 8.91, 11.76 Hz), 5.21 (dd, 1H, H-3, J =
3.14, 11.62 Hz), 5.26 (d, 1H, H-4, J = 2.52 Hz), 6.19 (d, 1H, H-1, J = 3.64 Hz),
6.61 (d, 1H, N-H, J = 8.88 Hz). 13C NMR (CDCl3): δ = 16.1, 20.7, 20.72, 20.90,
20.93, 46.7, 67.0, 68.1, 69.9, 91.4, 169.5, 170.6, 170.73, 170.75. MS (ESI): m/z
calculated: 331.13; m/z found: 354.1 (M+Na). The H-1–H-2 coupling constant
of 3.64 Hz is consistent with the alpha anomer of 9 reported previously by
Horton.[2]
N-Acetyl-α-L-fucosamine (1)
Deacetylation of 1,2,3,4-tetra-O-acetyl-α-L-fucosamine (9, 0.13 g, 0.39
mmol) was accomplished according to the method previously described by Hor-
ton and Anisuzzaman;[2] the residue obtained upon workup was extracted into
hot EtOAc, the solution evaporated, and the solid obtained recrystallized from
EtOH to afford N-acetyl-α-L-fucosamine (1) as colorless crystals that were suit-
1
able for X-ray diffraction analysis (0.075 g, 93.7%). H NMR (d6-DMSO): δ =
1.03 (d, 3H, H-6, J = 6.59 Hz), 1.80 (s, 3H, COCH3), 3.46 (d, 1H, H-4, J =
2.56 Hz), 3.60 (dd, 1H, H-2, J = 3.30, 11.35 Hz), 3.88 (dd, 1H, H-3, J = 3.30,
10.98 Hz), 3.93 (q, 1H, H-5, J = 6.59 Hz), 4.27 (d, 1H, OH, J = 7.32 Hz), 4.49
(d, 1H, OH, J = 4.39 Hz), 4.83 (t, 1H, H-1, J = 4.03 Hz), 6.25 (d, 1H, OH, J =
4.03 Hz), 7.52 (d, 1H, NH, J = 8.79 Hz). 13C NMR (d6-DMSO): δ = 18.5, 24.5,
51.5, 66.7, 69.0, 72.8, 92.5, 171.1. Spectra reported here are consistent with
those published by Horton,[2] and the structure of 1α is now confirmed here
independently by X-ray diffraction.
ACKNOWLEDGMENT
Financial support from the National Institutes of Health (1R15AI053112-
01), the National Science Foundation (CHE-0639196, DUE-0087210), and the
School of Graduate Studies and Research at Youngstown State University is
gratefully acknowledged. The X-ray diffractometer was funded by NSF Grant
0087210, Ohio Board of Regents Grant CAP-491, and by Youngstown State
University.
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