Glycals protonation

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. 

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 polarized-TT frontier molecular orbital (PPFMO) method has been employed to study protonation and sulphenylation of sugar-related dihydrofurans and tetrahydropy-rans. The predictions are consonant with the experimental observations62. Contrary to expectations, the proton-catalysed addition of alcohols to glycals, such as 30, has been shown by isotope labelling (2H) not to be anii-diaxial addition. This observation has been rationalized by the initial attack by deuteron from the bottom, giving ion 31, and by the anomeric effect favouring axial substituent at C-l (32)63. 

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

To avoid isolating the glycal, the reaction was quenched with an excess of borane in THF and, upon oxidative work-up under basic conditions, C-disaccharide 38 was obtained in 64% yield over two steps (Scheme 11) (77). The stereochemistry of the hydroboration step was verified on the corresponding acetate by examination of the Jy%T and J2 y coupling constants in the proton NMR spectra. 

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]. 

Lithio glycal is prepared by direct abstraction of a vinylic proton with butyl lithium or Schlos-ser s base (w-BuLi and t-BuOK). Alternatively, transmetalation of 1-stannyl-glycal with butyl... 

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... 

Under strongly acidic conditions, glycals add alcohols. The acid of choice is triphenylphosphine hydrobromide. The stereochemistry at Cl appears to be dictated by the position of anomeric equilibrium, with axial products predominating, except in the case of tribenzylallal, where they would be disfavoured by 1,3-diaxial interactions. Running the reaction in deuterated solvents gave a mixture of axial and equatorial deuterium at C2, with between 5 1 and 2 -l predominance of equatorial protonation, except for dibenzyl-3-deoxyglucal. ... 

The glycals react with water, alcohols, phenols, carboxylic acids, and certain bases, in the presence of an acidic catalyst, in the same way as does 2,3-dihydro-4/f-pyran (which gives, for example, 2-hydroxy-, 2-alkoxy-, and 2-aryloxy-tetrahydropyrans in high yield ). (Tetrahydro-pyranyl ethers are useful for protecting alcoholic groupings during reactions in basic media, and are readily hydrolyzed with acid,) The first step of these additions would be expected to be protonation at C-2, followed by attack of the nucleophilic reagent on the resonance-stabilized, C-1 carbonium ion. 

---