Linker Thioglycoside

The sulfoxide method has been applied to the concept [319,374] of intramolecular aglycone delivery for the formation of [1-mannosidcs by means of a silylene linker. In the original work, the acceptor and a thioglycoside donor were joined by means of a silylene group before the oxidation to the sulfoxide [141]. However, it was later found that the preformed sulfoxide was tolerated by the chemistry for the introduction of the linker [286,375]. The intramolecular aglycone delivery step was shown to function effectively for the transfer of the donor to the 2-, 3- and 6-position of glucopyr-anosides, as exemplified in Scheme 4.64. 

Zuurmond and co-workers146 have carried out a synthesis of the same haptenic oligosaccharide with linker-arm (72) using the four key synthons 73,74,76, and 77. The disarmed L-rhamnose thioglycoside 74 provides an excellent example... 

The iV-l-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl linker has also been introduced between the C2-amino group of the glucosamine and a solid-support [5]. This linker was stable during glycosylation with thioglycoside in the presence of methyl trifluoromethane sulfonate, but readily cleaved by hydrazine, primary amines, or even ammonia. 

In addition, a polymer-supported version of the intramolecular aglycon delivery was explored [148]. In this system, mannosyl thioglycoside 93 bound to polyethylene glycol (PEG) via a p-alkoxybenzyl linker was subjected to the two-step sequence and the resultant fi-manno-glycoside is specifically released into the non-polymeric phase, while most of the by-products remain bound to the polymer. 

Protected thioglycoside 15 was attached to the soluble polymer support via a DOX-linker 16 (Scheme 20.5) using the NIS/AgOTf protocol, followed by acidic hydrolysis of the acetal using acetic acid. Dissacharide 17 was coupled with glycosyl... 

Scheme 20.16 Block-type solid phase strategy employing a photolabile linker and thioglycoside building blocks. 

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