P-Mannosylation reaction

Subsequent work showed the novel p-mannosylation reaction to be independent of the stereochemistry at sulfur in the starting sulfoxide [20, 21], although rare examples of the opposite are known for the broader sulfoxide method [22], and independent of the anomeric configuration of the donor [21]. 

Interestingly, particularly in view of the relatively minor effect of silyl ethers and glycosidic bonds at 02, the 4,6-O-benzyIidene directed p-mannosylation reaction is highly sensitive to steric bulk in the protecting group for 03 [118]. Thus, a 2-O-benzyl-3-O-TBDMS protected draior was found to be considerably less selective than the 3-0-benzyl-2-0-TBDMS regioisomer toward a common acceptor (Scheme 24) [19, 118],... 

The serendipitous discovery of the 4,6-0-benzylidene directed p-mannosylation reaction and the subsequent attempts to apply, extend, and understand it led to a number of other fascinating and mostly unexpected discoveries. Of importance among these were the reversal of selectivity seen with the corresponding 4,6-0-benzylidene protected glucopyranosyl donors, the a-directing effect of the cw-fused 2,3-0-carbonate in homogeneous mannosylation and rhamnosylation... 

In many fungi a proportion of the wall mannan is labile to dilute alkali and oligosaccharides of mannose are released by a p-elimination reaction in its presence. This mannan is linked to serine or threonine residues in polypeptide by way of a mannosyl-hydroxyamino acid (>-glycosidic bond a linkage which has no known counterpart in higher animals. The synthesis of this structure has been studied in some detail in Saccharomyces cerevisiae, and there is evidence for similar mechanisms in other fungi. 

Knowledge of the contributions of individual substituents to the conformational preferences of oxocarbenium ions, however, is not sufficient to predict the reactivities of highly substituted systems such as those formed from carbohydrates. [Other intermediates, aside from discrete oxocarbenium ions, could also lead to the nucleophilic substitution products. For an example involving ion-pair intermediate, see Crich et al. [15].] For the type of substrates presented in this work, neither the Lewis acid nor the solvent has significant influence upon product distribution as described in Ref. [19]. For instance, although the influences of the C2, C3, and C4 substituents on the mannopyranosyl cation should reinforce each other to favor P-product, a-selectivity was observed upon allylation of the mannosyl phosphate 29 (Fig. 4.10) [Allylation of maimosyl phosphate 29 has been shown to be highly a-selective with MesSiOTf [67]. C-Mannosylation reactions are generally a-selective [68-76]. a-Selectivity was also observed with acetate-protected... 

Although it remains to be proved, it is logical to postulate that, if this most difficult of glycosylation reactions - the p-mannosylation - proceeds in a dissociative manner, such a pathway will operate for most other cases and the mechanism of Scheme 6, or its extended version in Scheme 7 will be general. 

P-Mannopyranosides with a chromo- or fluorogenic aromatic aglycone, e.g. a 4-nitrophenyl, naphthyl, or 4-methylumbelliferyl group, are valuable enzyme substrates. The 4-nitrophenyl derivative is also employed as a mannosyl donor in glycosidase-catalyzed p-mannosylation. These compounds can be prepared in 40 70% yields by reaction of the mannosyl bromide 2 [54] with sodium [202] or potassium phenolates [203, 204], Garegg has synthesized aryl P-mannosides in 50-65% yields by condensation of dicyclohexylidene-mannopyranose with phenols in the presence of diethyl azodicarboxylate and triphenylphosphine [44, 205]. Epimeriza-tion of C-2 of aryl P-D-glucopyranosides by the Lindberg protocol (Section 13.2.2) has also been described [206]. 

The use of silicon as a temporary tether in intramolecular reactions has found widespread application in organic chemistry [17]. This concept was first described by Stork et al. in 1992 for intramolecular stereocontrolled glycosidation reactions. With a silyl group connected to the 0-2 position of a P-mannosyl donor it was demonstrated that the glycosyl acceptors could contain primary and secondary hydroxyl groups [18, 19]. 

Glycosyl phosphorimidate donors were obtained by the synthetic sequence outlined in Scheme 6.14. These glycosyl donors were coupled with primary acceptor glycosides in moderate to excellent yields, and depending on the reaction conditions (Scheme 6.15) either a- or p-selcctivitics were observed.51 p-ScIcctivc mannosylations and glycosylation on reaction of secondary hydroxyl containing acceptors did not prove feasible. 

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