Polymer-supported glycosyl acceptors

Sulfoxide donors have been employed in the glycosylation of soluble and insoluble polymer-supported glycosyl acceptors, and the area has been reviewed [86,283]. 

SCHEME 10.8 The first glycosylation of polymer-supported glycosyl acceptors 15(i-5). 

While it is usually considered most efficient to conduct polymer-supported glycosylation by an acceptor-bound strategy [132, 133], consideration of the hydrolytic and thermal instability of the mannosyl triflate intermediates initially led to the development of a donor-bound strategy for the supported synthesis of the p-mannopyranosides. Thus, a polystyrylboronate resin was employed to capture a 4,6-diol leading to a resin bound donor that was activated and coupled under the standard BSP conditions. Excellent p-selectivities were obtained and the products cleaved from the resin with aqueous acetone (Scheme 11) [88]. 

Scheme 9.2 Comparison of polymer-supported synthesis of oligosaccharides between the attachment of a polymer to a glycosyl donor and a glycosyl acceptor.

Fig. 1. 1,6-Glycosylation with a glucose acceptor attached to a polymer support (P = solid support) and a trichloroacetimidate donor.

An acylated disaccharide 75 was efficiently prepared using polymer-supported reagents. Formation of glycosyl imidate 72 was carried out with Dowex 1-8X (OH form) as a polymer-supported base, and glycosylation of acceptor 73 with the imidate 72 was carried out using... 

SCHEME 54. Major concepts for the polymer-supported/solid-phase oligosaccharide synthesis glycosyl acceptor bound approach (A) and glycosyl donor bound approach (B). 

The validity of the approach was first demonstrated by the synthesis of a linear tetrasaccharide [22] and a hexasaccharide 13 [23] as outlined in Scheme 3. Polymer-bound galactal 5 was converted to the 1,2-anhydro sugar 6 by epoxidation with 3,3-dimethyldioxirane [24], Polymer-bound 6 acted as a glycosyl donor when reacted with a solution of 7 in the presence of zinc chloride, resulting in the formation of disaccharide 8a. Upon repetition, this glycosylation procedure accommodated the secondary alcohol glycosyl acceptor 10 as well as disaccharide acceptor 12. Huor-idolysis with tetrabutylammonium fluoride (TBAF) was used to cleave the desired products from the polymeric support and furnish hexasaccharide 13 in 29% overall yield from 5 [16]. 

To install the appropriate functionality at C2, solution phase chemistry has relied on a trans-diaxial addition of an iodonium electrophile in the presence of an amine to form an iodosulfonamide. Displacement of iodine proceeds presumably through an aziridine intermediate and may be induced by a thiolate nucleophile to fashion thioethyl 2-amidoglycosyl donors [38]. Successful transfer of this method to the solid support allowed polymer-bound glycals to be converted into thioethyl gly-cosyl donors. These donors were in turn coupled with a variety of glycosyl acceptors, including glycals [39]. 

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