Neuraminic acid analogues

Other useful nucleophiles for this type of substitution include azide and thiolacetic acid. Glaxo researchers utilized such a strategy in their synthesis of the neuraminic acid analogue 346 (Scheme 8.109). ° Itzstein and co-workers used a similar strategy to synthesize a thio analogue of neuraminic acid 347 °" and reported that thiolacetic acid was also a suitable nucleophile. ° ... 

Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. Furthermore, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. For example, the unnatural L-nucleoside 1 inhibits reverse transcriptase and shows potent and selective anti-AIDS activity,1 and the unsaturated neuraminic acid analogue 2 is the sialidase-inhibitory... 

Chain-extended Compounds.- A review with 200 references on recent advances in the synthesis of C, -Q sugars, including neuraminic acid analogues, has been published. ... 

A. Oseltamivir inhibits neuraminidase, an enzyme that cleaves neuraminic acid from oligosaccharides. Neuraminidase activity aids the movement of viral particles through neuraminic acid-rich respiratory secretions and is required for the release of progeny virions. Inhibition of viral DNA polymerase is the mechanism of action of nucleoside analogue antiviral drugs. Interferons do stimulate the JAK-STAT signaling pathway but do not stimulate proliferation of immune cells. Ribavirin inhibits GTP synthesis, and the antiretroviral protease inhibitors (e.g., ritonavir) inhibit HIV protease. 

Vorwerk, S. et al. Carbocyclic Analogues oj H-Acetyl-2,3-didehydro-2-deoxy-D-Neuraminic Acid (Neu5Ac2en, DANA) Synthesis and Inhibition of Viral and Bacterial Neuraminidase. 3.4.4 1998 [187]... 

Synthesis of GG167 is described [36] in the Scheme G. The most direct approach to the synthesis of DANA analogues starts fi om the commercially available N-acetyl-neuraminic acid. 

The second family of A-linked oligosaccharides are called the lactosamine family in which the D-mannose residues of the core pentasaccharide are substituted 1 2 by lactosamine, which is a lactose analogue with A-acetyl-D-glucosamine substituted for D-glucopyranose at the reducing-end of lactose. The lactosamine is frequently substituted by A-acetyl-D-neu-raminic acid (for the structure of A-acetyl-D-neuraminic acid, see the monomer residue in colominic acid,0 Sect. 8.2 andO Fig. 7) linked 2 3 or 2 6 [142,143]. The third family has a mixed structure of the high mannose and lactosamine families [144,145,146,147]. 

With neuraminic acid, a sugar amino acid widely occurring naturally as Ai-acetylneuraminic acid, an amide-linked (1 5)-dimer 21 (O Scheme 6) and the corresponding 2,3-ene analogue were prepared [30], On a solid phase, even an octamer 22 was available [31]. 

Introduction of a fluoride at the 3-position of neuraminic acid yielded a compound (57) that was a competitive inhibitor of the a-(2,6)-sialyl-trans-ferase. Base and sugar-modified analogues of CMP-Neu5Ac have also been prepared to investigate the tolerance of oc-(2,6)-sialyl-transferase to base exchange (58) and modification of the 5-, 8- or 9-position of neuraminic acid (59), (60). While base-exchange was not tolerated, modifications of the acid moiety yielded compounds that were substrates for the enzyme. 

A review on the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics features the use of aldolases in the synthesis of neuraminic acid and KDO analogues. ... 

A new 8-step synthesis of the neuraminidase inhibitor 19 from neuraminic acid has been outlined, and a number of analogues 18 with modified substituents on N-5, as well as a 6-thio-analogue, " have been prepared and evaluated as neuraminidase inhibitors. The carboxamides 20 and 21 have also been synthe-... 

A short review (11 pages, 14 references) on the synthesis and evaluation of mechanism-based inhibitors of Kdo8P synthase has appeared. " A review on the alkaline biocatalysis for the direct biosynthesis of iV-acetyl-D-neuraminic acid (NeuSAc) from iV-acetyl-D-glucosamine has also been written. The syntheses of furanose derivatives of 3-deoxy-D-cryt/iro-2-hexulosonic acid and their 3-bromo and 3-deuterio analogues have been reported. 3-Deoxyoctulosonic acid 16 has been prepared by use of E. coli heptulosonate synthase (Scheme 6). ... 

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