Intramolecular aglycone delivery

SCHEME 4.8 IAD (a) by the use of anomeric linkers, (b) by the use of rigid spacers at nonreacting centers, and (c) by tethering from C2 to form 1,2-cw-glycosides. 

SCHEME 4.10 Trapping of an intermediate oxocarbenium ion using a 3-0-TMS ether in the synthesis of fS-L-rhamnosides. Naph, 2-naphthyl. 

SCHEME 4.11 Dual anomeric control using IAD in the synthesis of a,a-trehalose. PCB, 

The method worked well on simple molecules however, its extension to higher oligosaccharides and complex structures had limited success [66]. 

In a different version of the same concept. Stork [67,68] and Bols [69-72] introduced silylene type tethering with glycosyl sulfoxide [67,68] or thioglycoside [69-72] donors. The silicon-tethered acceptor approach was also extended to the synthesis of a-D-gluco- [70,72] and a-D-galactopyranosyl linkages in oligosaccharides [70,72]. 

As illustrated, the trisaccharide donor (149), with a p-methoxybenzyl ether function at 0-2, and the chitobiose acceptor (150) were tethered using DDQ. The resulting mixed acetal (151) was 

SCHEME 5.26 Intramolecular aglycone delivery using isopropylidene ketal tethering. 

The use of the p-methoxybenzyhdene acetal tethered intramolecular aglycone dehvery was extended to polymer-supported oligosaccharide synthesis [77], The method also proved to be successful in the synthesis of other difficult linkages, such as (3-D-fructofuranosides [78], P-D-arabinofuranosides [79-81] and a-D-fucofuranosides [82], 

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

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. 

Sulfoxide-mediated intramolecular aglycone delivery has been conducted with a temporary linker formed in situ by the reaction of lanthanide triflates with the donor and acceptor-based alcohols (Scheme 4.66) [336], However, as the selectivities recorded were modest, it has to be assumed that intermolecular glycosylation was an important side reaction in this chemistry. 

Scheme 4.64 Sulfoxide-mediated intramolecular aglycone delivery.

Additional aspects of intramolecular aglycone delivery are discussed in Section 5.4. 

Scheme 4.66 Intramolecular aglycone delivery via metal complexes.

Scheme 16 Intramolecular aglycon delivery approach using NAP ether protected glycosyl donors.

Scheme 7.18 p-Methoxybenzyl-assisted intramolecular aglycon delivery. 

INTRAMOLECULAR AGLYCON DELIVERY ON POLYMER SUPPORT GATEKEEPER-CONTROLLED GLYCOSYLATION... 

Scheme 7.23 Intramolecular aglycon delivery on polymer support.

Ito, Y. Ogawa, T., Intramolecular aglycon delivery on polymer support Gatekeeper monitored glycosylation. J. Am. Chem. Soc. 1997, 119, 5562-5566. 

Barresi, F. Hindsgaul, O., Synthesis of Beta-Marmopyranosides by Intramolecular Aglycon Delivery. J. Chem. Soc. 1991, 113, 9376-9377. 

Scheme 15. The polymer-bound alkoxybenzyl protecting group in 67 serves as a directing group and enabled the intramolecular aglycon delivery to afford a stereoselective formation of /1-mannosides 69. Byproducts such as 70 and 71 remained on the polymeric support.

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