Glycoside sialic acid

A New Approach to Sialic Acid Glycosides. One of the key steps in our synthesis of NeuSAc was the addition of methanol to 10. The furan presumably stabilizes the cation formed by protonation of the [3-carbon of the glycal. Indeed, as discussed at the outset, the de facto nucleophilic character of the furan was one feature which recommended its use. 

The use of S-2-phenylselenopropanal in the synthesis of the naturally occurring (8R) antipode of the title compound is described. This chemistry was adapted to achieve a total synthesis of a sialic acid glycoside in a stereospecific fashion. 

Finally, in the case of compound 17, the system was transformed to the sialic acid glycoside 20. The key step in this regard was the benzoyl migration... 

The successful application of compound 16 to the synthesis of sialic acid glycosides points to the need for a more direct and efficient route to such systems. Partial synthesis from carbohydrate sources would be a promising alternative to total synthesis. This goal and the goal of extending the scope of the exchange reaction to include secondary sugar alcohol substrates, are now important objectives of our laboratory. 

In order to examine the substructural determinants of sialic acid required for MAG binding, a second study by Kelm and coworkers [33] evaluated the inhibitory potential of simple sialic acid glycosides towards MAG and sialoadhesin using their hapten inhibition assay (Table 16.4). 

Scheme 2 Early demonstration of the active-latent glycosylation strategy using sialic acid glycosides [22]...

The preparation of the complex aminoalditol 29 as a neuraminidase resistant derivative of sialic acid glycosides has been disclosed. ... 

The sensitivity of the resorcinol/Cu " method can be increased significantly (between 3- to 6-fold), if periodate oxidation is carried out prior to heating with the resorcinol/Cu strong acid reagent (Jourdian et al 1971 Table 1). The chromogen formed with sialic acid glycosides under the influence of periodate is stable to further oxidation at 37 °C and leads to a chromophore with an extinction maximum at 630 nm. The chromogen formed with free sialic acids is destroyed at... 

As mentioned above, the periodic acid/thiobarbituric acid methods only function with free sialic acids. This means that prior release of glycosidically bound sialic acids must be undertaken before analysis. Care should be taken in the case of sialic acid glycosides known to break down under the conditions of the assay, e.g. CMP-p-Neu5Ac (Aminoff 1961) and various synthetic ketosides of sialic acid (Meindl and Tupfy 1967, Khorlin et al. 1970). This inevitably leads to erroneous values of free sialic acid and involves other parameters which need consideration. These are discussed below in II. 10. 

The identification of CMP-NeuAcyl as the sialic acid donor in sialyltransfer reactions was made by Comb et al. (1966) in bacterial systems. In mammalian systems isolation of CMP-sialic acid glycosides labelled in the sialic acid moiety has been reported (Harms et al. 1973, Corfield ei al. 1976, Briles et al. 1977). Conclusive identification of cytosine as the nucleoside in such experiments has been presented by Carey and Hirschberg (1979) in mouse liver and kidney. The transfer reaction can be formulated as follows ... 

The enzyme is quite specific for CMP-p-NeuSAc and is distinct from nonspecific phosphodiesterase of nucleotide pyrophosphatase activities which do not cleave CMP-Neu5Ac. It may thus be considered as a p-sialidase, CMP-Neu5Ac being the only known natural sialic acid glycoside in p-linkage (Haverkamp et al. 1979 b). 

One particular exosialidase, from the loach Misgurnus fossilis, is specialized for cleaving 2-keto-3-deoxy-D-g/yc ro-D-ga/acr6>-nononic acid (Kdn) residues (Section 2), and can therefore be described as a Kdn ase (Li et al., 1993). It also acts slowly on sialic acid glycosidic linkages. 

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