Anomerization of glycosides

Esterification and transesterification using TiIV compounds are useful methods for functionalization of ester moieties under mild conditions. In the transformation of carboxylic acids to esters, a catalytic amount of TiCl(OTf)3 is effective (Scheme 30).110 Titanium alkoxides, such as Ti(OEt)4 or Ti(0 Pr)4, easily promote transesterification of alkoxy groups to other ones—even to more hindered groups.111 Anomerization of glycosides to Q-isomers using a Tilv-bascd Lewis acid is an important method for controlling the product structure.112... 

In order to minimize such possible side-reactions as anomerization of glycosides and acetolysis of acetal structures, alternative techniques of acetylation have been studied. Whereas basic catalysis leads to severe complications in certain nitro sugar derivatives (see Section IV,2a and c pp. 124, 129), boron trifluoride etherate has proved to be an excellent agent for satisfactory acetylation of glycosides, O-benzyl-idenated glycosides, and disaccharides that contain a deoxynitro function.148,149... 

The subject of anomerization of glycosides was briefly discussed in Section II. 1. Because of the anomeric effect (Section VII), a-glycosides are generally more stable than the (3-glycosides, and anomerization of a (3-glycoside in the presence of acid tends to produce an equilibrium mixture in which the a anomer predominates. 

The stereochemistry and points of connection of glycosidic bonds are commonly designated by symbols such as a(l 4) for maltose and (3(1 4) for cellobiose a and (3 designate the stereochemistry at the anomeric position the numerals specify the ring car bons involved... 

This reaction has been used m an imaginative way to determine the ring size of glycosides Once all the free hydroxyl groups of a glycoside have been methylated the glycoside is subjected to acid catalyzed hydrolysis Only the anomeric methoxy group IS hydrolyzed under these conditions—another example of the ease of carbocation for matron at the anomeric position... 

Scheme 5. Acid-induced anomerization of the gilvocarcin-type glycosidic linkage.

NMR spectroscopy To identify specific sugars, their sequence, linkages, and the anomeric nature of glycosidic linkages. 

The enzymes are available from a variety of sources and are often specific for certain types of glycosidic linkages and also for their anomeric natures. The sites of action of endoglycosidases F and H are shown in Figure 47-5. F acts on both high-mannose and complex oligosaccharides, whereas FI acts on the former. 

In summary, for O-glycosides, a-anomers (a-D and oc-l) are thermodynamically more stable than the p-anomers (p-D and p-L) due to the anomeric effect. Therefore l,2-c -a-D- or a-L-glycosides are preferentially obtained, in general. On the other hand, the lower stability of glycosides such as p-D-arabinosides and p-D-mannosides requires special methods for their preparation, thus promoting the development of new synthetic methodologies. 

The trichloroacetimidate method for glycoside synthesis extended its versatility right at the outset (51,52a) by exhibiting an especially smooth reaction of 0-(glycosyl)trichloroacetimidates with Bransted acids. Without the addition of any catalyst, simple Bransted acids are able to substitute the trichloroacetimidate group at room temperature in high yields, as shown (17) for la-a in Scheme 6. Because of anomerization of possible / products... 

Reduction of aldonolactones and their derivatives with isotopically modified reducing agents leads to sugars labeled at the anomeric center. Glycosides substituted with deuterium or labeled with tritium are widely employed for kinetic isotope-effect measurements, mechanistic studies, isotope-tracing experiments, and so on. 

Y, then C-OR bond breaking should be even more dependent on, and thus sensitive to, the orientation of the lone pairs on the single donor oxygen of [91], This conclusion is relevant to the reactions of glycosides, and has important implications for the enzyme-catalysed reactions at their anomeric centres. 

---