Anhydro Sugars as Glycosyl Donors

Scheme 5.37 illustrates solid-phase oligosaccharide synthesis using glycal-derived 1,2-anhydro sugars as glycosyl donors [105]. 

An hydro Sugars as Glycosyl Donors 5.2.3.1 1,2-Anhydro Sugars... 

Scheme 27. 2,6-Anhydro-2-thio sugars as glycosyl donors for the stereospecific synthesis of 2-deoxy-a- and fl-glycosides.

Figure 1. Synthesis of the CDE trisaccharide of olivomycin A with 2,6-anhydro-2-thio sugars as glycosyl donors.

Anhydro sugars were first obtained by multistep synthesis, the first report of such a derivatives being by Brigl.177 Their potential as glycosyl donors was subsequently explored in disaccharide synthesis, but at that stage they did not enjoy widespread use.178-181... 

Anhydro sugars have proven to be versatile glycosyl donors for the preparation of many glycoconjugates. The 1,2-anhydro bridge is an epoxide that is also part of an acetal and is responsible for the unique reactivity of 1,2-anhydrohexopyranoses. The first well-defined member of this class was prepared by treatment of the partially functionalized pyra-nose (17) with ammonia in benzene, and is commonly referred to as BrigTs anhydride (O Scheme 15) [46]. 

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]. 

Tatsuta and Toshima [73] designed conformationally rigid 2,6-anhydro-2-thio sugars for the stereocontrolled synthesis of 2,6-dideoxy-a- and -P-glycosides which are very commonly found in bioactive natural products. These new donors have a very rigid structure (boat conformation) and the stereoselectivity of the glycosylation should not be affected by the anomeric effect in the same manner as the more usual chair conformers. 

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