Hexasaccharide synthesis using glycosyl

Scheme 4. Synthesis of hexasaccharide 20 using glycosyl phosphates.

Included are two examples of the two- and three-step sequential oligosaccharide assembly to illustrate Approach A. The first synthesis makes use of trichloroacetimidate 239, which is selectively activated over the thioglycoside acceptor 240 with TMSOTf (Scheme 49). The SPh moiety of the resulting tetrasaccharide is then activated over the added glycosyl acceptor 241 by addition of NIS and TfOH to provide hexasaccharide 242 in 50% yield over two steps.100 This approach combines advantages of the selective activation, convergent block strategy, and one-pot synthesis. 

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]. 

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]. 

The synthesis of a series of amine-funetionalized heparin tetra-saccharide (117) and hexasaccharides (118, 119) was performed (Fig. 5) using a n -h 2 modular approach. The conditions of the glycosylation reactions were carefully optimized to produce efficiently the desired synthetic intermediates with an N-ben lorgrearbonyl-protected ami-noethyl spacer at the reducing end. The use of microwave heating greatly facilitates O- and N-sulphation steps. ... 

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