Anhydro sugars reactivity

Structure and Reactivity of Anhydro-sugars. Part I. Branched-chain Sugars. Part I. Action of Di-ethylmagnesium on Methyl 2 3-Anhydro-4 6-0-benzylidene-a-D-mannoside, A. B. Foster, W. G. Overend, M. Stacey, and G. Vaughan,/. Chem. Soc., (1953) 3308-3313. 

Comprehensive reviews of the chemistry of both the glycals [105-107] and anhydro sugars [108,109] have appeared in the recent literature. This chapter will attempt to summarize what is known about their preparation and reactivity in the formation of the glycosidic linkage and highlight recent examples to emphasize practical and strategic considerations in the choice of glycosyl donors. 

There are several instances where reactive intermediates present during the synthesis of septanosides have reacted intramolecularly to give ring-contracted or bicyclic products.91 Similar intramolecular reactions (such as the formation of 1,6-anhydro sugars) have precedents in the pyranose literature. Such cases of intramolecular reactivity described in the literature notably involve novel ethers or thioethers as the nucleophilic species in the ring contractions. 

Copolymerization has been used for evaluating the reactivity of the monomeric, anhydro sugar derivatives, and also to prepare stereoregular polysaccharides of structures more complex than those of those prepared from a single monomer.98-104,107 The procedure adopted has been first to determine the reactivity ratios of the monomers, and then to perform preparative experiments under conditions that provide polysaccharides having the desired, copolymer composition. 

Reactivity Ratios of Copolymerizations of 1,6-Anhydro Sugars, Calculated by Various Methods... 

Since the oxolane ring is relatively stable toward acids and bases, the reactivity of these anhydro sugars is predetermined mainly by the presence of a free or potential aldehyde group. 

R. J. Ferrier, W. G. Overend, and A. E. Ryan, Structure and reactivity of anhydro-sugars. 4. The action of alkali on 2-deoxy-D-glucose structure of isoglucal, J. Chem. Soc., (1962) 1488-1490. 

C. A. Johnson and P. H. Gross, Heterocyclic amino sugar derivatives. 6. Stabilization of a reactive intermediate by steric hindrance. Mechanism of 3,6-anhydro sugar formation, J. Org. Chem., 38 (1973) 2509-2512. 

Pazue, John H and Aronson, N. N., Jr., Glycoenzymes Enzymes of Glycoprotein Structure, 27, 301-341 Peat, Stanley, The Chemistry of Anhydro Sugars, 2, 37-77 Peat, Stanley. See also, Bourne, E. J. PERCIVAL, E. G. V., The Structure and Reactivity of the Hydrazone and Osazone Derivatives of the Sugars,... 

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]. 

These important factors constitute the proper strategy for the regioselective protection of the remaining active centers of the molecules as their reactivity varies significantly. Thus, the relative reactivity of the various -OH groups upon stereoselective tosylation of 1,6-anhydro sugars decreases according to the determined order as depicted inO Fig. 1 [27]. 

Whereas these are the only selected examples of unusual chemical reactivity of 1,6-anhy-drosugars, the other anhydrosugars such as 3,6-anhydro [37] are worthy of mention on the basis of their special chemical character of increased reactivity of the epoxide toward reactive nucleophiles. Some of the physico-chemical properties of 1,6-anhydro-sugars are listed in O Table 6. 

These data indicate that the reactions of the (3-anomers proceed through the mechanism in Figure 3.31, in which the react initially to give a 1,2-anhydro sugar (whose protected derivatives are comparatively stable compounds). This has only access to the 7/4, 7/5, and B o conformations, since the epoxide ring ensures the coplanarity of C3, C2, Cl and 05. In the 774 and B o conformations, the ionised 6-OH is ideally placed to open the 1,2-epoxide. The reactive conformations of the glycosides themselves are probably somewhere on the skew-boat pseudorotational itinerary around °5 2. 

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