Neu5Ac precursor

There is some evidence for the occurrence of a glycolyl group at 0-4 of Neu5Ac in serum and submandibular-gland glycoproteins from the horse, based on biosynthetic studies with radioactive precursors,33 and chemical and t.l.c. analysis of the sialic acid ester groups.74... 

The pathway of the biosynthesis of Neu5Ac demonstrates the origin of sialic acids from the cellular hexose and hexosamine pools. These sugars are, therefore, suitable components for the study of the biosynthesis of sialic acid. However, only ManNAc has been shown to be a relatively specific precursor of sialic acids, as may be seen from the distribution of radioactivity between the individual monosaccharides of glycoconjugates after incubation. Injections of radioactive ManNAc into animals, or incubation of surviving tissue slices or individual cells with this compound, give incorporation of label mainly into the sialic acids.226 227... 

Figure 2 Mammalian monosaccharides and nucleotide sugars. (A) Chemical structures, common names, and abbreviations of the 11 monosaccharides found in mammalian glycans as well as ManNAc, the precursor for sialic acids. (B) Examples of the three classes of nucleotide sugars are provided by UDP-GIcNAc (Glc, GIcA, Gal, GalNAc, and Xyl also use UDP), GDP-Man (Fuc also is linked to GDP), and CMP-Neu5Ac/Gc (IdoA is produced by postsynthetic epimerization of GIcA and therefore does not require a nucleotide sugar).

In 1991, the syntheses of sialyl C-glycosides were introduced by Bednarski et ah, Paulsen et ah, and Vasella et al. Bednarski and Paulsen exploited a 2-halogeno derivative of Neu5Ac as a precursor of the anomeric radical, which was anticipated to be stabilized by the capto-dative effect of the C1 carboxylate group and ring oxygen. Bednarski reacted the 2-chloro derivative 195 with allyltributyltin and a catalytic amount of bis(tributyltin), and photolized for 18 h to obtain C-glycoside 196 as a 1/1 of anomeric mixture in 65% yield (O Scheme 53) [129]. 

It was more recently shown that the stable and crystalline 2-pyridyl sulfide of Neu5Ac derivative 204 is also an excellent precursor of the anomeric organometallic species, in this samari-um-Reformatsky procedure [96] (O Scheme 42). 

The first total synthesis of Neu5Ac from non-carbohydrate precursor has been reported by Danishefsky et al. in 1988, who used a hetero Diels-Alder reaction between a diene and an aldehyde to establish the pyranoid ring [135] (Scheme 48). 

The total synthesis of sialosides by using the chemoenzymatic approach is as follows [74]. Sialic acid itself can be synthesized from ManNAc, mannose, or their derivatives by sialic acid aldolase enzyme through aldol condensation reaction. If ManNAc is chemically or enzymatically modified at C2, C4—C6 positions, sialic acid has structural modifications at C5, C7-C9 positions, respectively. The sialic acids are subsequently activated by a CMP-siahc acid synthetase to form a CMP-sialic acid, which is the donor used by sialyltransferases. Because CMP-sialic acid is tmstable, the CMP-Neu5Ac synthetase is valuable for the preparative enzymatic synthesis of sialosides. In the last steps, the CMP-sialic acid is transferred to galactose or GalNAc terminated glycosides by sialyltransferases to form structurally defined sialosides. Examples are that Chen and co-workers have recently developed a one-pot multienzyme system for the efficient synthesis of a-sialosides (Table 2) [12,76,79]. In this system, recombinant E. coli K-12 sialic acid aldolase catalyzed the synthesis of sialic acid precursors for... 

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