Anomeric substitution

An extensive AMI semiempirical study on a wide range of anomerically substituted acetamides was published in the first major paper describing this reaction. For rearrangement of 221, enthalpies of activation were clearly lowered in the sequence... 

Amides substituted at nitrogen with both a sulfur and oxygen have only been generated as reactive intermediates. Sulfur is less electronegative than nitrogen and its role in anomeric substitution at nitrogen should be radically different. 

The addition of CF3TMS on a lactone group in position 1 allows introduction of CF3 on the anomeric position. Due to its electron-withdrawing effect, the CF3 group inhibits the possible formation of the oxocarbenium ion intermediate of the anomeric substitution. Consequently, the substiment introduced on the anomeric position (OAc,... 

In the case of 1-halogeno 1-deoxy sugars, the competition of photobromination at C-5 or C-l depends on the halogen and its configuration. The regioselectivity of the reaction at C-l decreases from anomeric chlorides to fluorides, and the a-deri-vatives are less reactive or inert for the anomeric substitution. 

Bohtt, V, Mioskowski, C, Falck, J R, Direct anomeric substitution of pyranyl esters using organocopper reagents. Tetrahedron Lett., 30, 6027-6030, 1989. 

Bromine can be introduced directly into particular ring positions of certain sugar derivatives by free radical processes which can show high selectivity and efficiency. For example, peracety-lated glucose 90 is selectively brominated at the C-5 position by NBS yielding 91 however, in the case of glycosyl halides, such as tetra-O-acetyl- -D-glucopyranosyl chloride 92, anomeric substituted product 93 is mainly formed (O Scheme 47) [79,80]. 

Synthesis of glycosides of the required structure (and configuration) from the appropriate sugars and alcohols or phenols has been discussed in the preceding Sections. In this Section, the transformation of one glycoside into another, whether by anomerization, substitution of one aglycon for another, or alteration of the sugar residue, will mainly be dealt with. 

J. M. Kim and R. Roy, Phase transfer catalyzed anomeric substitutions with o-xylopyranosyl halides, J. Carbohydr. Chem., 16 (1997) 1281-1292. 

An important characterization parameter for ceUulose ethers, in addition to the chemical nature of the substituent, is the extent of substitution. As the Haworth representation of the ceUulose polymer shows, it is a linear, unbranched polysaccharide composed of glucopyranose (anhydroglucose) monosaccharide units linked through thek 1,4 positions by the P anomeric configuration. 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

The magnitude of the anomeric effect depends on the nature of the substituent and decreases with increasing dielectric constant of the medium. The effect of the substituent can be seen by comparing the related 2-chloro- and 2-methoxy-substituted tetrahydropy-rans in entries 2 apd 3. The 2-chloro compound exhibits a significantly greater preference for the axial orientation than the 2-methoxy compound. Entry 3 also provides data relative to the effect of solvent polarity it is observed that the equilibrium constant is larger in carbon tetrachloride (e = 2.2) than in acetonitrile (e = 37.5). 

The stereoselectivity of these reactions has been interpreted in terms of chair-like six-membered ring transition states in which the substituents a to tin adopt an axial position, possibly because of steric and anomeric effects. The cc-substituted (Z)-isomers are less reactive because the axial preference of the a-substituent would lead to severe 1,3-diaxial interactions17. 

The second separation method involves n.O.e. experiments in combination with non-selective relaxation-rate measurements. One example concerns the orientation of the anomeric hydroxyl group of molecule 2 in Me2SO solution. By measuring nonselective spin-lattice relaxation-rat s and n.0.e. values for OH-1, H-1, H-2, H-3, and H-4, and solving the system of Eq. 13, the various py values were calculated. Using these and the correlation time, t, obtained by C relaxation measurements, the various interproton distances were calculated. The distances between the ring protons of 2, as well as the computer-simulated values for the H-l,OH and H-2,OH distances was commensurate with a dihedral angle of 60 30° for the H-l-C-l-OH array, as had also been deduced by the deuterium-substitution method mentioned earlier. 

From simple chemical-shift considerations, it would be expected that one / -D-Gal residue will give rise to an anomeric chemical-shift of 104.2 p.p.m., together with one / -D-Man residue whose substituted signal C-3 occurs at 75-80 p.p.m., and one terminal a-D-Man residue whose C-l signal occurs at 103.66 p.p.m. Although these SRR data do not define a unique structure for this glycopeptide, they do indicate the types of residues that are present. The glycopeptide structure discussed had previously been determined to be that depicted in 11. It may, indeed, be... 

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