Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks

Article abstract of DOI:10.1016/j.carres.2019.107900

Reported herein is the synthesis of a number of building blocks of 2-amino-2-deoxy-D-mannose from common D-glucose precursors.

Full text of DOI:10.1016/j.carres.2019.107900

Journal Pre-proof
Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as
versatile building blocks
Catherine Alex, Satsawat Visansirikul, Yongzhen Zhang, Jagodige P. Yasomanee,
Jeroen Codee, Alexei V. Demchenko
PII:
S0008-6215(19)30687-1
DOI:
https://doi.org/10.1016/j.carres.2019.107900
CAR 107900
Reference:
To appear in: Carbohydrate Research
Received Date: 24 November 2019
Revised Date: 20 December 2019
Accepted Date: 20 December 2019
Please cite this article as: C. Alex, S. Visansirikul, Y. Zhang, J.P. Yasomanee, J. Codee, A.V.
Demchenko, Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile
building blocks, Carbohydrate Research (2020), doi: https://doi.org/10.1016/j.carres.2019.107900.
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Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno
derivatives as versatile building blocks
a
a,b
c
a
Catherine Alex, Satsawat Visansirikul, Yongzhen Zhang, Jagodige P. Yasomanee, Jeroen
c
a,
Codee, and Alexei V. Demchenko *
a
Department of Chemistry and Biochemistry, University of Missouri – St. Louis, One University Boulevard, St. Louis,
Missouri 63121, USA
b
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuddhaya Road, Ra-
jathevee, Bangkok, 10400, Thailand
c
Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Nether-
lands
Supporting Information Placeholder
24,25
glucopyranosides 1 and 6.
As previously shown by Knapp
ABSTRACT: Reported herein is the synthesis of a number of
building blocks of 2-amino-2-deoxy-D-mannose from com-
mon D-glucose precursors.
2
3
et al, high regioselectivity of sulfonation of diol 1 with triflic
anhydride in pyridine toward the C-2 position could be
achieved at low temperature. The resulting 2-O-triflate was
then subjected to the nucleophilic displacement with sodium
azide in DMF to afford 2-azido-2-deoxy-D-mannopyranoside
intermediate 2 (Scheme 1). This two-step protocol represent
a common approach to obtain rare or inaccessible amino-
sugars. The latter can be used for a number of pathways
that is showcased herein by two synthetic transformations.
First, treatment of compound 2 with zinc in the presence of
acetic anhydride provided direct transformation of the 2-
azido into 2-acetamido group. As a result, ManNAc deriva-
tive 3 was obtained in 78% yield. It should be noted that de-
rivatives 2 and 3 can be used as glycosyl acceptors or as in-
termediates to access other functionalized derivatives. In
addition, while we were specifically targeting 2-azido and 2-
acetamido derivatives, many other N-protecting groups can
be introduced after the azide reduction step, if so desired.
All oligosaccharides comprise an oligomeric sequence
wherein monomers are linked via O-glycosidic linkages. This
type of linkage is obtained by a glycosylation reaction, which,
in spite of significant progress, remains challenging due to
2
6
1,2
the requirement to achieve high stereocontrol and suppress
3
,4
side reactions. Due to significant advances, many glycans
can now be obtained by using chemical methods and auto-
5
mated platforms in solution and on solid phases. However,
poor accessibility to sugar building blocks hampers devel-
opment of all synthetic approaches. Things are further com-
plicated because “unlike the synthesis of peptides and oligo-
nucleotides, there are no universal building blocks or methods
6
for the synthesis of all glycans.” In spite of general improve-
ments in application of protecting groups in the mainstream
Scheme 1. The synthesis of D-mannosamine building
blocks 2-5 from D-gluco derivative 1
7
-12
carbohydrate research,
building blocks for the introduc-
tion of uncommon (rare) sugars remain largely underdevel-
13
oped or not available at all. Reported herein are reliable and
scalable procedures for the synthesis of mannosamine build-
ing blocks.
N-Acetylmannosamine (ManNAc) is the biosynthetic pre-
1
4,15
cursor of N-acetylneuraminic acid
many bacterial glycans.
and a constituent of
16-18
Hence, a considerable interest has
been devoted to the synthesis of ManNAc and its derivatives.
Nevertheless, mannosamine remains prohibitively expensive
as the starting material both for the laboratory and industrial
application. The total synthesis from D-arabinose reported
19
by O’Neill and alkaline-mediated epimerization of C-2 in N-
2
0
acetylglucosamine by Spivak and Roseman are the classics
of the synthesis of ManNAc. More recently, building blocks
of ManNAc have been prepared via the inversion of configu-
2
1-23
ration at C-2 of D-glucose with nitrogen nucleophiles.
Reported herein are two modes to obtain ManNAc deriva-
tives from methyl 4,6-O-benzylidene-α and β-D-

In summary, presented herein is an efficient synthesis of a
variety of 2-amino-2-deoxy derivatives of D-mannose. We
investigated gram-scale syntheses, and the developed proto-
cols appear to be sufficiently straightforward and reliable to
be attempted at a greater scale if needed. The utility of these
building blocks has been demonstrated by the synthesis of
glycosyl acceptors 2, 3 and 8 as well as thioglycoside donor 5.
While we were specifically targeting 2-azido and 2-acetamido
derivatives, many other N-protecting groups can be intro-
duced, if necessary. Further application of these versatile
building blocks, both as glycosyl donors and as glycosyl ac-
ceptors, are currently underway in our laboratories.
We also performed acetolysis of intermediate 2 with acetic
anhydride in the presence of H SO . This reaction led to con-
2
4
comitant replacement of methyl glycoside and benzylidene
acetal with acetyl groups. As a result, tetraacetate 4 was
smoothly produced in 80% yield. The latter derivative can be
used as a versatile intermediate for further functionalization.
Herein, tetraacetate 4 was reacted with ethane thiol in the
presence of BF etherate. As a result, ethylthio glycoside 5
Experimental
3
was produced in 58% yield. While thioglycosides can be used
as versatile building blocks and as glycosyl donors, the syn-
thesis of other types of glycosyl donors or building blocks
can be readily achieved using similar synthetic routes.
General methods. Solvents were purified according to
standard procedures. Reactions were performed using
29
commercial reagents (Millipore Sigma, Carbosynth, TCI, or
Acros), and monitored by TLC on Kieselgel 60 F254 (EM Sci-
ence). Compounds were detected by UV light and by char-
ring with 10% sulfuric acid in methanol. Solvents were re-
The second approach to produce mannosamine derivatives
described herein involves adaptation of the O-
trichloroacetimidoyl protecting group migration approach
developed by van der Marel and co-workers for the synthesis
o
moved under reduced pressure at <40 C. Column chroma-
tography was performed on silica gel 60 (70-230 mesh). Opti-
cal rotations were measured at ‘Jasco P-2000’ polarimeter at
2
7,28
of other aminosugar targets.
This was affected by regiose-
1
13
lective O-imidoylation at the C-3 position of diol 6. Preferen-
tial substitution at the C-3 position was achieved with tri-
chloroacetonitrile in the presence of DBU at room tempera-
ture. Subsequent in-situ sulfonation with triflic anhydride in
pyridine at C-2 followed by the treatment with DIPEA led to
the formation of 2,3-N,O-oxazoline 7, all in one pot. The in-
termediate 7 was isolated in 44% yield over three steps. The
fair yield is due to marginal regioselectivity obtained during
the first step and the necessity to separate product 7 from the
resulting side products. The oxazoline ring in derivative 7
was hydrolyzed by reaction with sodium hydroxide. The
amine group in the resulting partially protected derivative
was then chemoselectively N-acetylated to afford ManNAc
derivative 8. While we were specifically interested in obtain-
ing 2-acetamido derivatives, many other N-protecting groups
can be introduced after the oxazoline ring removal, if so de-
sired. The resulting 3-OH derivative 8 can be used as a glyco-
syl acceptor directly, or employed in further functionaliza-
tion per specific synthetic targets.
22 °C. H and C NMR spectra were recorded at 300 and 75
MHz, respectively, with a Bruker Avance spectrometer. The
chemical shifts are referenced to the signal of the residual
CHCl (δ = 7.27 ppm, δ = 77.23 ppm) for solutions in CDCl .
COSY and HMQC experiments were done to aid nuclei as-
signments. HRMS were recorded with a JEOL MStation
(JMS-700) Mass Spectrometer. Melting points were measured
at Digimelt MPA 160 melting point apparatus.
3
H
C
3
Methyl
2-azido-4,6-O-benzylidene-2-deoxy-α-D-
mannopyranoside (2). Pyridine (14 mL, 173.8 mmol) and
trifluoromethanesulfonic anhydride (Tf O, 0.65 mL, 3.87
2
o
mmol) were added at -30 C under argon to a stirred solution
of methyl 4,6-O-benzylidene-α-D-glucopyranoside (1, 0.99 g,
3
2 2
.52 mmol) in CH Cl (14 mL) and the resulting mixture was
o
stirred at -30 C for 3 h. The volatiles were removed under
reduced pressure, and the residue was dried in vacuo for 2 h.
Sodium azide (NaN , 1.14 g, 17.6 mmol) was added to a solu-
3
tion of the residue in DMF (15 mL) and the resulting mixture
o
was stirred at 75 C for 12 h. After that, the reaction mixture
Scheme 2. The synthesis of D-mannosamine building
block 8
was allowed to cool to rt, volatiles were removed under re-
duced pressure, and the residue was purified by column
chromatography on silica gel (EtOAc-hexane gradient elu-
tion) to afford the title compound (0.874 g, 2.84 mmol) in
8
0% as a pale-yellow syrup. Analytical data for 2: R 0.7
f
1
(
EtOAc-hexanes, 2/3, v/v). [α]
D 3
+70.8 (c 1.0, CHCl ); H NMR:
δ, 2.60 (s, 1H, 3-OH), 3.39 (s, 3H, OCH ), 3.72-3.87 (m, 2H, H-
3

5
, 6a), 3.91 (dd, 1H, J4,5 = 7.6 Hz, H-4), 3.99 (dd, 1H, J2,3 = 3.9
CH Cl (~150 mL) and was washed with H O (50 mL), sat. aq.
2
2
2
Hz, H-2), 4.21-4.32 (m, 2H, J3,4 = 7.6 Hz, H-3, 6b), 4.70 (d, 1H,
J1,2 = 1.1 Hz, H-1), 5.58 (s, 1H, CHPh), 7.34-7.44 (m, 3H, aro-
NaHCO
3
(50 mL), and H
2
O (2 x 50 mL). The organic layer
was separated, dried, and volatiles were removed under re-
duced pressure. The residue was purified by column chroma-
tography on silica gel (ethyl acetate-hexanes gradient elu-
tion) to afford the title compound (1.31 g, 3.49 mmol) as a
pale-yellow syrup in 58% yield. Analytical data for 5: R 0.7
(EtOAc/hexanes, 1/1, v/v); [α] +26.6 (c 1.0, CHCl ); H NMR:
13
matic), 7.45-7.54 (m, 2H, aromatic) ppm; C NMR: δ, 55.3
OCH ), 63.4 (C-5), 63.8 (C-2), 68.8 (C-6), 69.0 (C-3), 79.1 (C-
(
3
4
), 100.2 (C-1), 102.4 (CHPh), 126.4, 128.5, 129.4, 137.2 (6C,
+
aromatic) ppm; HR-FAB MS: [M+Na]
calcd for
f
1
C H N O Na, 330.1066; found, 330.1069. Partial characteriza-
1
4
17
3
5
D
3
2
D
5
30
13
tion data [α]
reported previously.
+69.5 (c 1.1, CHCl
3
)
and C NMR for 2 were
δ, 1.35 (t, 3H, J = 7.4 Hz, SCH
2
CH
3
), 2.09, 2.13, 2.13 (3 s, 9H,
2
2
COCH ), 2.59-2.78 (m, 2H, SCH CH ), 4.09-4.17 (m, 2H, H-2,
3
2
3
6
a), 4.29-4.42 (m, 2H, H-5, 6b), 5.30-5.42 (m, 3H, H-1, 3, 4)
Methyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-
mannopyranoside (3). Acetic acid (2.0 mL, 30.7 mmol),
13
ppm; C NMR: δ, 14.7, 20.6, 20.7, 20.8, 25.5, 62.1, 62.8, 66.1,
6
calcd for C H N O SNa, 398.0998; found, 398.1003.
+
8.8, 71.3, 82.3, 169.6, 170.0, 170.8 ppm; HR-FAB MS: [M+Na]
acetic anhydride (Ac O, 2.0 mL, 18.6 mmol), and zinc dust
2
(
2.0 g, 26.9 mmol) were added to a solution of methyl 2-
azido-4,6-O-benzylidene-2-deoxy-α-D-mannopyranoside (2,
.83 g, 2.72 mmol) in THF (10 mL) and the resulting mixture
14 21
3
7
Methyl
4,6-O-benzylidene-2-deoxy-2N,3O-(2,2,2-
0
trichloroethylidene)-β-D-mannopyranoside (7). Trichlo-
was stirred under argon for 1 h at rt. The solids were filtered
off through a pad of Celite, volatiles were removed under
reduced pressure, and the residue was purified by column
roacetonitrile (CCl CN, 535 µL, 5.33 mmol) and activated
molecular sieves (3 Å, 1.20 g) were added to a solution of 6
3
2 2
(1.25 g, 4.44 mmol) in CH Cl (50 mL) and the resulting mix-
chromatography on silica gel (MeOH-CH Cl2 gradient elu-
tion) to afford the title compound (0.68 g, 2.10 mmol) as
ture was stirred under argon for 15 min at rt. After that, DBU
(67 µL, 0.44 mmol) was added, and the reaction mixture was
stirred for 5 h at rt. The mixture was then cooled to -30 C,
2
o
white crystals in 78% yield. Analytical data for 3: m.p. 227-
°
2
(
28 C (CH
2
Cl
2
– hexanes); [α]
D
+40.5 (c 1.0, CHCl
3
); R
f
0.6
2
pyridine (1.79 mL, 22.2 mmol) and Tf O (897 µL, 5.33 mmol)
1
MeOH/CH Cl , 1/9, v/v); H NMR: δ, 2.07 (s, 3H, COCH3),
were added, and the resulting mixture was stirred under ar-
2
2
o
3
.38 (s, 3H, OCH ), 3.66 (dd, 1H, J = 9.4 Hz, H-4), 3.75-3.92
gon for 2 h at -30 C. The cooling was removed, N,N-
3
4,5
(
m, 2H, H-5, 6a), 4.25-4.34 (m, 2H, H-3, 6b), 4.45 (br ddd, 1H,
diisopropylethylamine (DIPEA, 7.7 mL, 44.4 mmol) was add-
ed, and the bright-red colored mixture was stirred under
argon for 12 h at rt. The volatiles were removed under re-
duced pressure and the residue was purified by column
chromatography on silica gel (EtOAc-hexanes gradient elu-
tion) to afford the title compound (805 mg, 1.97 mmol) as
H-2), 4.77 (d, 1H, J1,2 = 0.8 Hz, H-1), 5.59 (s, 1H, CHPh), 5.85
(
7
5
7
br d, 1H, J2,NH = 7.0 Hz, NH), 7.33-7.39 (m, 3H, aromatic),
13
.45-7.51 (m, 2H, aromatic) ppm; C NMR: δ, 23.5 (COCH3),
3.6 (C-2), 55.4 (OCH ), 62.8 (C-5), 67.2 (C-3), 68.9 (C-6),
9.7 (C-4), 100.8 (C-1), 102.5 (CHPh), 126.4, 128.5, 129.4, 137.1
3
+
(
6C, aromatic), 171.8 (C=O) ppm; HR-FAB MS: [M+Na] calcd
colorless crystals in 44% yield. Analytical data for 7: R
f
0.6
°
for C H NO Na, 346.1267; found, 346.1261.
(EtOAc/hexanes, 2/3, v/v); m.p. 164-165 C (from aq. MeOH);
16
21
6
1
[
α] -76.5 (c 1.0, CHCl ); H NMR: δ, 3.46 (s, 3H, OCH ), 3.64
D 3 3
1
,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-D-
(
m, 1H, J5,6a = 10.1 Hz, J5,6b = 4.4 Hz, H-5), 3.72 (dd, 1H, J6a,6b
=
mannopyranose (4). Sulfuric acid (0.2 mL, 3.73 mmol) was
added dropwise to a solution of 2 (0.76 g, 2.47 mmol) in ace-
tic anhydride (10.0 mL, 106.0 mmol) at 0 C. The external
cooling was removed, and the resulting mixture was stirred
under argon for 4 h at rt. Sat. aq. NaHCO was added careful-
ly to the reaction mixture until gas evolution has ceased.
EtOAc (30 mL) was added, and the resulting mixture was
washed with sat. aq. NaHCO
1
0.0 Hz, H-6a), 4.38 (dd, 1H, H-6b), 4.56-5.65 (m, 2H, H-2, 4),
.92 (d, 1H, J1,2 = 3.5 Hz, H-1), 5.02 (dd, 1H, J2,3 = 7.4, J3,4 = 9.8
Hz, H-3), 5.61 (s, 1H, CHPh), 7.34-7.42 (m, 3H, aromatic),
°
4
1
3
7
.46-7.55 (m, 2H, aromatic) ppm; C NMR: δ, 56.1 (OCH
3
),
3
6
4.5 (C-5), 67.4 (C-2), 70.3 (C-6), 76.9 (C-4), 77.4 (CCl ), 82.6
3
(
C-3), 97.5 (C-1), 101.8 (CHPh), 126.4, 128.5, 129.5, 136.9 (6C,
+
aromatic), 164.7 (C=N) ppm; HR-FAB MS: [M+Na] calcd for
C H Cl NO Na, 429.9992; found, 429.9980.
3
. The organic layer was separat-
ed, dried over Na SO , and filtered. Volatiles were removed
16 16
3
5
2
4
under reduced pressure and the residue was co-evaporated
with toluene. The resulting residue was purified by column
chromatography on silica gel (ethyl acetate-hexanes gradient
elution) to afford the title compound (0.74 g, 1.97 mmol) as a
Methyl 2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-
mannopyranoside (8). 1 M aq. NaOH (10 mL) was added
dropwise to a solution of 7 (559 mg, 1.37 mmol) in MeOH (30
mL) and the resulting mixture was kept for 12 h at reflux (~65
C). The reaction mixture was allowed to cool to rt, the vola-
tiles were removed under reduced pressure, and the residue
o
pale-yellow amorphous solid in 80% yield (α/β = 7/1). Analyt-
1
ical data for 4: R
f
0.5 (EtOAc/hexanes, 1/1, v/v); H NMR: δ,
2
2
2
2
.11, 2.15, 2.17, 2.22 (4 s, 12H, 4 x COCH ), 4.04-4.20 (m, 3H, H-
was dried in vacuo for 1 h. The crude residue was dissolved in
3
, 5, 6a), 4.30 (dd, 1H, J = 4.5, 12.4 Hz, H-6a), 5.39-5.50 (m,
2
MeOH (15 mL), Ac O (0.65 mL, 6.91 mmol) was added, and
13
H, H-3, 4), 6.17 (d, 1H, J = 1.9 Hz, H-1) ppm; C NMR: δ, 20.6,
the resulting mixture was stirred under argon for 2 h at rt.
After that, volatiles were removed, and the residue was puri-
fied by column chromatography on silica gel (MeOH-CH Cl
0.7, 20.8, 20.9, 60.5, 61.8, 65.3, 70.6, 70.7, 91.3, 168.3, 169.4,
+
1
70.1, 170.8 ppm; HR-FAB MS: [M+Na] calcd for
2
2
C H N O Na, 396.1019; found, 396.1024.
gradient elution) to afford the title compound (252 mg, 0.78
mmol) as a white amorphous solid in 58% yield. Analytical
14
19
3
9
Ethyl
3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-thio-α-D-
o
data for 8: Rf 0.5 (MeOH/CH Cl , 1/9, v/v); m.p. 217-219 C
mannopyranoside (5). Boron trifluoride diethyl etherate
2
2
1
(
2
5
from CH
2
Cl -42.0 (c 1.0, CHCl
.11 (s, 3H, COCH ), 3.46 (m, 1H, J
5,6a
2
-hexane); [α]
D
3
); H NMR: δ,
(
(
3.05 mL, 24.05 mmol) was added dropwise to a solution of 4
= 10.2, J5,6b = 4.9 Hz, H-
2.24 g, 6.01 mmol) and ethane thiol (0.89 mL, 12.03 mmol) in
3
°
3
), 3.52 (s, 3H, OCH ), 3.70 (dd, 1H, J4,5 = 9.4 Hz, H-4), 3.80
CH Cl (50 mL) at 0 C. The external cooling was then re-
2
2
(
3
dd, 1H, J6a, 6b = 10.2 Hz, H-6a), 4.00 (dd, 1H, J3,4 = 9.5 Hz, H-
), 4.34 (dd, 1H, H-6b), 4.52 (br dd, 1H, J2,3 = 4.0 Hz, H-2),
moved and the resulting mixture was stirred under argon for
6 h at rt. After that, the reaction mixture was diluted with
1

4
.64 (d, 1H, J1,2 = 1.7 Hz, H-1), 5.57 (s, 1H, CHPh), 5.98 (br d,
Groups – Strategies and Applications in Carbohydrate Chemistry;
Vidal, S., Ed.; Wiley-VCH: Weinheim, 2019; pp 1-28.
(12) Wang, T.; Demchenko, A. V. Synthesis of carbohydrate building
blocks via regioselective uniform protection/deprotection
strategies. Org. Biomol. Chem. 2019, 17, 4934-4950.
(13) Emmadi, M.; Kulkarni, S. S. Recent advances in synthesis of
bacterial rare sugar building blocks and their applications. Nat.
Prod. Rep. 2014, 31, 870-879.
14) Varki, A. Biological roles of oligosaccharides: all of the theories
are correct. Glycobiology 1993, 3, 97-130.
1
H, J2,NH = 6.0 Hz, NH), 7.30-7.40 (m, 3H, aromatic), 7.44-7.53
13
(
m, 2H, aromatic) ppm; C NMR: δ, 23.3 (COCH ), 54.9 (C-2),
3
5
7.3 (OCH
3
), 67.4 (C-5), 68.6 (C-6), 71.6 (C-3), 79.7 (C-4),
1
00.6 (C-1), 102.3 (CHPh), 126.4, 128.4, 129.3, 137.1 (6C, aro-
+
matic), 173.8 (C=O) ppm; HR-FAB MS: [M+Na] calcd for
C H NO Na, 346.1267; found, 346.1254.
16
21
6
(
ASSOCIATED CONTENT
Supporting Information
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15) Angata, T.; Varki, A. Chemical diversity in the sialic acids and
related a-keto acids: an evolutionary perspective. Chem. Rev.
2
002, 102, 439-469.
NMR spectra for all new compounds. This material is availa-
ble free of charge via the Internet at
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Cappelletti, E.; Tontini, M.; Berti, F.; Lay, L.; Costantino, P.;
Adamo, R. Synthesis of Staphylococcus aureus type 5 Capsular
Polysaccharide Repeating Unit Using Novel L-FucNAc and D-
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AUTHOR INFORMATION
Corresponding Author
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17) Gagarinov, I. A.; Fang, T.; Liu, L.; Srivastava, A. D.; Boons, G. J.
Synthesis of Staphylococcus aureus Type Trisaccharide
Repeating Unit: Solving the Problem of Lactamization. Org. Lett.
015, 17, 928-931.
*
Department of Chemistry and Biochemistry, University of
5
Missouri – St. Louis, One University Boulevard, St. Louis,
Missouri 63121, USA; demchenkoa@umsl.edu
2
(
18) Visansirikul, S.; Yasomanee, J. P.; Pornsuriyasak, P.; Kamat, M.
N.; Podvalnyy, N. M.; Gobble, C. P.; Thompson, M.; Kolodziej,
S. A.; Demchenko, A. V. A Concise Synthesis of the Repeating
Unit of Capsular Polysaccharide Staphylococcus aureus Type 8.
Org. Lett. 2015, 17, 2382-2384.
Author Contributions
The manuscript was written through contributions of all
authors. / All authors have given approval to the final version
of the manuscript.
(
(
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20) Spivak, C. T.; Roseman, S. Preparation of N-Acetyl-D-
mannosamine (2-Acetamido-2-deoxy-D-mannose) and D-
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Notes
The authors declare no competing financial interests.
(
21) Draghetti, V.; Poletti, L.; Prosperi, D.; Lay, L. A Convenient
Multigram Preparation of Functionalized 2-Azido-2-Deoxy-D-
Mannose as a Useful Orthogonally Protected Building Block for
Oligosaccharide Synthesis. J. Carbohydr. Chem. 2001, 20, 813-
ACKNOWLEDGMENT
This work was supported by the National Science Foundation
(
CHE-1800350) and National Institute of General Medical
8
19.
Sciences (GM120673).
(
(
22) Popelova, A.; Kefurt, K.; Hlavackova, M.; Moravcova, J. A
concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-
acetamido-2-deoxy-D-mannopyranosides. Carbohydr. Res. 2005,
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5

•
Chemical synthesis of a variety of derivatives of mannosamine has been completed using
different approaches;
•
•
•
The synthesized compounds can be used as glycosyl donors or glycosyl acceptors directly;
Other modifications of protecting and/or leaving groups can be easily incorporated;
The developed approaches are expected to expedite the synthesis of microbial glycans
containing 2-acetamido-D-manno residues

The authors have no conflicts to declare