P-mannoside

Special topics (synthesis of P-mannosides, furanosides, sialosides, glycosides of aminosugars and deoxysugars, if applicable)... 

P-Mannosides are difficult to introduce because the axial C-2 substituent of a mannosyl donor sterically and electronically disfavors nucleophilic attack from the P-face. P-Mannosides have been obtained by the direct substitution of a-glycosyl triflates, which are conveniently prepared by the treatment of an anomeric sulfoxide with triflic anhydride (Tf20) or thioglycosides with NIS (Scheme 4.3a)... 

An intramolecular acetal has also been introduced by the treatment of a mixture of a 1-thio-mannoside, having a methoxybenzyl protecting group at C-2 and an alcohol with DDQ [71] (Scheme 4.4c). Activation of the thioglycoside with methyl triflate gave a P-mannoside as the only anomer. This approach was employed for the synthesis of the core pentasaccharide of N-linked glycoproteins. 

Scheme 4.4 Synthesis of P-mannosides by intramolecular aglycon delivery.

Scheme 5.27 NPOE-based strategy for preparation of P-mannosides.

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

The potential of the mannuronate ester donors in the formation of the p-mannosidic linkage has been demonstrated with the construction of a mannuronic acid alginate pentamer using a convergent orthogonal glycosylation.64... 

Scheme 6.9 Formation of P-mannosides using glycosyl phosphates...

Hodosi and Kovac reported the highly efficient P-mannosylation, which makes use of mannose-derived 1,2-O-stannylene acetal 15 in combination with an aglycon-derived triflate (Scheme 7.13).58 A remarkable feature of this method is its extreme simplicity. Even totally unprotected mannose can be used as precursor of 15. Undoubtedly, this method can be seen as one of the most facile methods for the stereoselective synthesis of P-mannosides. 

Another interesting approach was developed by Ikegami and coworkers, who used an anomeric orthoester as the key intermediate (Scheme 7.14).59 Formation of orthoester 16 from lactone was effected by TMSOTf and TMSOMe. Subsequent Lewis acid mediated reduction afforded p-mannoside in high selectivity, presumably because of the stereoelectronically controlled hydride delivery from the a face. 

Scheme 9.12 Reverse use of a polymer support for the synthesis of P-mannoside linkage. The synthetic helper arm (MPEG), together with other polymer-bound by products, is removed from the desired product by simple precipitation.

Beta-mannosidase and P-mannanase cleave the P-mannoside linkages in P-l,4-D-... 

On the other hand, the synthesis of p-mannosides continues to be a major obstacle. The most commonly used procedure involves mannosyl bromides as donors and insoluble silver salts as promoters [3j. However, the coupling often gives appreciable amounts of the undesired a-anomer. Recent approaches to p-mannosides are based on participation from the 2-position [4], and the desired p-anomers can thereby be obtained exclusively. However, these procedures often require multiple steps for preparation of the key interme-diate(s). 

P Mannosides have also been prepared by direct substitution of an a-manno-glycosyl tosylate donor.17 However, this method has not been... 

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