Support-bound glycosyl acceptors

IV. STRATEGIES USING SUPPORT-BOUND GLYCOSYL ACCEPTORS... 

Support-derived trisaccharide building block 79 was used in a block synthesis of dodecasaccharide 82 (Scheme 13 p. 23). Reaction of support-bound glycosyl acceptor 78 with 79 furnished hexasaccharide 81. Removal of a silyl protecting group and coupling with trisaccharide donor 79 was repeated twice, followed by photolytic cleavage of the linker to furnish dodecasaccharide 82 in 10% yield from 73 [64]. 

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

Scheme 1 Glycosyl acceptor (Case 1) and donor (Case 2) bound to the solid support, and bidirectional synthesis (Case 3) S, solid support P, unique protecting group X, activating group asterisk, uniquely differentiated hydroxyl group.

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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