Protonation of Glycals

These results are consistent with an Ad 2 (addition-electrophilic-bimolecular) mechanism for a first step of protonation, followed by a glycosyl transfer usually directed by the kinetic anomeric effect. Theoretical calculations [13] have shown 

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Table 5.5 Sugar stereochemistry at Cl and C2 resulting from protonation of glycals...

Kaila N, Blumenstein M, Bielawska H, Franck RW (1992) Face selectivity of the protonation of glycals. J Org Chem 57 4576-4578... 

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. 

Acid-catalyzed addition of methanol to the glycal proceeds by regioselective protonation of the dou-... 

The stereochemistry of 3-C-nitro glycals has been studied in some detail [210]. For example, when nitroanhydroglucitol 106 was subjected to reaction with triethylamine, it gave the elimination product 107, which was then rearranged to an equilibrated mixture of glycals 108 and 109 (O Scheme 36) [211,212]. Some researchers have tried to explain this equilibrium shift by arguing that the quasi-equatorial anomeric proton is made more acidic by the stereoelectronic effect [213]. 

Before starting any structural modulation, we first evaluated the effect of the C-9-C-10 unsaturation on antimalarial activity and ascertained that the presence of a CF3 group at C-10 could disfavor the protonation leading to oxonium 14, and hence the further gluc-uronidation (see Scheme 6.4). The antimalarial activities of glycals 10 and 18 have been assessed and compared (see Figure 6.3) [58], Whereas in vitro activities on P. falciparum... 

Acid-catalyzed addition of methanol to the glycal proceeds by regioselective protonation of the double bond in the direction that leads to the more stable carbocation. Here again, the more stable car-bocation is the one stabilized by the ring oxygen. 

The proton-catalyzed addition of alcohols to glycals is shown not to be trans diaxial addition. Bollitt et al. [83] reported that triphenylphosphine hydrobromide (TPP-HBr) was the catalyst of choice for mild and high-yield protonation and subsequent glycosidation of glycals (Fig. 5.44). 

In addition to well-resolved one-dimensional (ID) 1H and 13C spectra, which are usually sufficient for monitoring synthetic steps, HR-MAS techniques can be applied to two-dimensional (2D) homonuclear and heteronuclear experiments, which allow a wealth of structural information to be obtained. H,13C HMQC (heteronuclear multiple quantum coherence) spectra are particularly useful in the analysis of solid support-bound oligosaccharides, since the anomeric protons exhibit characteristic resonances. Such a spectrum of a polymer-bound trisaccharide glycal is shown in Figure 8.4. 

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