Download N-Acetylneuraminic acid

N-Acetylneuraminic acid
NHAc
Product Code: MA00746
CAS Number: 131-48-6
Chemical Formula: C 11 H 19 NO 9
Molecular Weight: 134.13
Synonyms:
O
HO
OH
HO
OH
CO2H
OH
Sialic acid
Neu5Ac
Sialic acid is a commonly used generic term for O- or N-substituted derivatives of the ninecarbon monosaccharide neuraminic acid. N-Acetylneuraminic acid is the most common derivative
found in mammalian cells, and sialic acid is often used to refer specifically to this molecule. The
abbreviations Neu5Ac or NANA are also used.
N-Acetylneuraminic acid is widely distributed in human tissues and is found in glycoproteins on
cell membranes and in glycolipids such as gangliosides, and is involved in diverse biological
functions including neurotransmission, leukocyte extravasation, viral or bacterial infections and
carbohydrate-protein recognition events leading to cell adhesion.1,2 N-Acetylneuraminic acid is
also found in several body fluids such as saliva, urine, amniotic fluid and cerebrospinal fluid.
As a negatively charged, non-reducing sugar, N-Acetylneuraminic acid is more difficult to analyse
directly than reducing sugars such as glucose or lactose. Enzymatic methods for detection in
fluids such as serum have been developed, which rely upon the cleavage of pyruvic acid from the
molecule by N-acetylneuraminic acid aldolase (also known as N-acetylneuraminate pyruvate
lyase), forming N-acetylmannosamine (ManNAc), Scheme 1.3,4 Subsequent oxidation of pyruvic
acid to hydrogen peroxide by pyruvate oxidase and colourimetric detection, or reduction of
pyruvic acid by lactate dehydrogenase in the presence of NADH and photometric detection form
the basis of the quantitative analytical methods.
OH
HO
H
HO
O
O
CO2H
OH
N
H
N-Acetylneuraminic
acid aldolase
O
HO
HO
O
+
NHAc
HO
OH
OH
OH
O
Pyruvic acid
ManNAc
Scheme 1
Neuraminidase enzymes (sialidases) cleave N-Acetylneuraminic acid and related sialic acids from
glycoproteins and glycolipids. Influenza viruses require neuraminidase activity to degrade cellsurface receptors, facilitating release of viral particles from infected cells.5 Neuraminidase
inhibitors such as Zanamivir and Oseltamivir (Scheme 2) are effective influenza treatments.6,7 A
colourimetric assay for sialidase activity using the Neu5Ac derivative 5-bromo-4-chloro-3-indolylα-D-N-acetylneuraminic acid 1 (Product code EB02506) has been reported as a test for bacterial
vaginosis, a condition associated with endometriosis and pre-term labour.8
Carbosynth Limited
8&9 Old Station Business ParkCarbosynth
- ComptonLimited
- Berkshire - RG20 6NE - UK
8&9 Old
Station Business Park - Compton
- Berkshire
- RG20
UK 579444
www.carbosynth.com
[email protected]
Tel: +44 1635
578444
Fax: 6NE
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OH
HO
H
HO
O
O
CO2H
O
O
HN
NH2
Zanamivir
CO2H Cl
O
Br
O
NHAc
NH2
NH
H
HO
NHAc
NHAc
OH
HO
N
H
OH
Oseltamivir
1
Scheme 2
The utility of N-acetylneuraminic acid in synthetic carbohydrate chemistry has proved
challenging, and the development of new methodology for O-sialations is an active field of
research.9,10 Ikeda and co-workers have reported the synthesis of phenyl 2-α-selenoglycosides
(4) and glycosyl thioimidates (5) of N-acetylneuraminic acid, readily formed in two steps from
the methyl ester of Neu5Ac (2), Scheme 3.11,12 Derivatives 4 and 5 are subsequently used as
glycosyl donors in glycosylation reactions, as shown in Scheme 4 for the coupling of 5 with
protected galactose 6 as the acceptor.
OAc
OR
OR
H
O
OR
CO2Me
PhSeH, i-Pr2NEt
or :
OAc
X
1,3-benzothiazole-2-thiol
i-Pr2NEt, CH2Cl2
NHAc
OR
AcCl
2, R=H, X=OH
OAc
H
O
4, Y =
CO2Me
Se
Y
NHAc
5, Y =
OAc
N
S
S
3, R=Ac, X=Cl
Scheme 3
AcO
O
HO
+
5
O
O
AgOTf, CH2Cl2, rt
O
AcO
OAc
H
O
O
AcHN
O
OAc
6
CO2Me
O
O
O
O
O
54%, a:b = 1:3
Scheme 4
References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Rahmann, H.; Rosner, H.; Breer, H. J. Theor. Biol. 1976, 57, 231.
Szabo, Z. B.; Borbas, A.; Bajza, I.; Liptak, A.; Antus, S. Tetrahedron Lett. 2008, 49, 1196.
Sugahara, K.; Sugimoto, K.; Nomura, O.; Usui, T. Clin. Chim. Acta 1980, 108, 493.
Kolisis, F. N. Biotechnol. Appl. Biochem. 1986, 8, 148.
Resende, R.; Glover, C.; Watts, A. G. Tetrahedron Lett. 2009, 50, 4009.
Von Itzstein, M.; Wu, W.-Y.; Jin, B. Carbohydr. Res. 1994, 259, 301.
Eisenberg, E. J.; Bidgood, A.; Cundy, K. C. Antimicrob. Agents Chemother. 1997, 41, 1949.
Wiggins, R.; Crowley, T.; Horner, P. J.; Soothill, P. W.; Millar, M. R.; Corfield, A. P. J. Clin. Microbiol. 2000, 38, 3096.
Boons, G.-J.; Demchenko, A. V. Chem. Rev. 2000, 100, 4539.
Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W. L. Chem. Rev. 2002, 102, 2227.
Ikeda, K.; Sugiyama, Y.; Tanaka, K.; Sato, M. Bioorg. Med. Chem. Lett. 2002, 12, 2309.
Ikeda, K.; Aizawa, M.; Sato, K.; Sato, M. Bioorg. Med. Chem. Lett. 2006, 16, 2618.
Carbosynth Limited
8&9 Old Station Business ParkCarbosynth
- ComptonLimited
- Berkshire - RG20 6NE - UK
8&9 Old
Station Business Park - Compton
- Berkshire
- RG20
UK 579444
www.carbosynth.com
[email protected]
Tel: +44 1635
578444
Fax: 6NE
+44 -1635
www.carbosynth.com [email protected] Tel: +44 1635 578444 Fax: +44 1635 579444