Sialic acids unsaturated

K. Ikeda, Y. Ueno, S. Kitani, R. Nishino, and M. Sato, Ferrier glycosylation reaction catalyzed by Bi(OTf)3-Montmorillonite K-10 Efficient synthesis of 3,4-unsaturated sialic acid derivatives, Synlett (2008) 1027-1030. 

P. Florio, R. J. Thomson, A. Alafaci, S. Abo, and M. von Itzstein, Synthesis of 8 4-P-d-glucopyranosiduronic acids as mimetics of 2,3-unsaturated sialic acids for sialidase inhibition, Bioorg. Med. Chem. Lett., 9 (1999) 2065-2068. 

The reaction of unsaturated sialic acid with xenon difluoride was also studied in the similar fashion (Figure 7). Methyl 4,7,8,9-tetra- -acetyl-2,3-dehydro-2-deo>y -N-acetylneuraminate (20)(2 ) reacted with xenon difluoride in methylene chloride in the presence of boron trifluorideetherate in an oxygen atmosphere to give the... 

The set of variously iV-acylated 2,3-unsaturated sialic acids 70 was synthesized to probe the activity of the sialidase of Vibrio cholerae, the causative agent of cholera. Syntheses of a range of fluorinated analogues of the methyl glycoside of 4-(2,4-dihydroxybutryoyl)amino-2,6-dideoxy-D-mannopyranose, the monosaccharide determinant of Vibrio cholerae are covered in Chapter 8. 

Scheme 12 Completion of the synthesis of zanamivir and 2,3-unsaturated sialic acid (Neu5Ac2en) analogues. Reagents and conditions a) Me3SiN3 (1.5 equiv), t-BuOH, 90 °C, 13 h 96% b) i) ln(0) (2 equiv), NH4CI, EtOH, 80 °C, 12 h ii) LiOH, THE, rt, 2 h 90% for the 2 steps c) aminoiminomethanesulfonic acid, K2CO3, water, 77% d) LiOH (2 equiv), THE, rt, 2 h 90%.

Scheme 13 Application to the synthesis of of zanamivir analogues 46 and 49 and 2,3-unsaturated sialic acid 45 and 46.

The next substantial progress was the determination of the X-ray structure of neuraminidase (sialidase) complexed with sialic acid (PDB entry 2bat) [23,24]. Analysis of the binding mode of sialic acid shows that it exhibits numerous polar contacts. Especially the interaction with a cluster of three Arg residues is very prominent. It is notable that the sialic acid adopts a rather planar unusual boat conformation again orientating its carboxylic acid optimal in the direction of the above mentioned arginine residues. Thus, this boat conformation, as unsaturated 2-deoxy-2,3-dehydrosialic acid, resembles the geometry of the transition state. 

In the area of longer-chain systems, the dideoxy-heptonolactone 4 has been made using a Wittig reaction on unprotected D-arabinose, and a dr-selective Wittig reaction was also used to prepare the unsaturated lactone 5, potentially useful for the synthesis of sialic acids and analogues, from 2,4 5,6-di-0-isopropylidene-a/deAydo-D-glucose.l3 2,4-O-Benzylidene-L-xylose was converted, by Wittig reaction and one-carbon chain extension at C-5, into the carboxylate 6, which was... 

The unsaturated sialic acid could also be obtained by prolonged heating (5 h, 90 °C) of 2,4,7,8,9-penta-O-acetyl-N-acetylneuraminic acid in dioxan, followed by O-deacetylation (Meindl and Tuppy 1969 a). 

The synthesis of unsaturated 4-azido-sialic acid derivatives is covered in Chapter 10, and the synthesis of 2-acetamido-l,2-dideoxynojirimycin in Chapter 18. 

Shukla, A. K., Schroder, C., Nohle, U., and Schauer, R., 1987, Natural occurrence and preparation of O-acetylated 2,3-unsaturated sialic acids, Carbohydr. Res. 168 199-209. 

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