Anomeric stereocenter

SCHEME 16.26 Distal-selective dipolar cycloaddition with a nitronate bearing a single anomeric stereocenter. 

Patemo-Biichi reaction between 2-methylfuran 31 and an a-hydroxyaldehyde 30 to form the core oxetane. Two of the three stereocenters set in the electrocyclization appear in the final product while the third is selectively reversed with anomeric assistance. 

When a monosaccharide forms a cyclic hemiacetal (or hemiketal), the carbonyl carbon becomes a stereocenter. Thus, cyclization leads to formation of two possible stereoisomers. These isomers are called anomers, and the former carbonyl carbon is called the anomeric carbon. The isomer with the anomeric OH (shown in blue) pointed down is the alpha anomer. The isomer with the anomeric OH (shown in blue) pointed up is the beta anomer. (Figure 12.14)... 

In an effort to address the medicinal chemist s need for new synthetic methods for the preparation of unnatural carbohydrates, new de novo methods for carbohydrate synthesis have been developed. These routes use asymmetric catalysis to set the sugar absolute stereochemistry, a palladium-catalyzed glycosylation reaction to stereoselectively control the anomeric center, and subsequent diastereoselective post-glycosylation to install the remaining sugar stereocenters. The utility of this method has been demonstrated by the syntheses of several classes of mono-, di- and tri-saccharides. 

The control of anomeric stereochemistry continues to fuel the investigation into the synthetic utility of (x-oxygenated radical intermediates. Moreover, it has proven to be a valuable tool in organic synthesis, especially in the stereoselective synthesis of various substituted tetrahydropyrans, y>>n-l,3-dioxanes, and carbohydrate derivatives. The recent discovery of non-equilibrium radical reactions and conformation-induced self-regeneration of stereocenters should provide new opportunities in the ever-expanding field of a-oxygenated radical chemistry. 

Anomers Sugar hemiacetals, diastereomers with [Pg.254]

The stereocenters at C(2) and C(3) of 4 were conveniently established with the correct relative and absolute configurations once again through the utilization of the aldol methodology developed by Evans.l 7,20 Thus, reaction of furaldehyde (46) with the boron enolate 47 followed by methanolysis afforded the P-hydroxy ester 48 in enantiomerically pure form. The sequential reaction of 48 with bromine in methanol and then aqueous acid followed by protection of the intermediate anomeric lactols... 

For a comprehensive explanation of carbcAydrate nomenclature, see A.D. McNaught, Carbohydr. Res. 1997, 297, 1. Therein, designations of a- and P-anomeric stereochemistry are explained for substrates that lack a C-5 stereocenter. 

The new stereocenter resulting from cyclic hemiacetal formation is referred to as an anomeric carbon. The stereoisomers thus formed are called anomers. 

As stated previously, polymer stereochemistry depends critically upon the structures of the monomers and how they are assembled. No new stereocenters are produced when amino acids are combined to make proteins, or nucleotides are combined to make nucleic acids. This is because the linkages created in forming the polymers are not stereogenic. The same is not true for polysaccharides, where the newly formed anomeric center is stereogenic. We will consider these three types of biopolymers separately. 

Hydroformylation with the BIPHEPHOS ligand is a slow process reqiiireing 5 days at 65°C to proceed. The domino hydroformylation allylboration hydroformylation sequence resulted in a mixture of anomeric lactols (48%). In order to facilitate product analysis this mixture was directly oxidized to the corresponding lactones 62 and 63 (63%). The diastereomeric lactones were obtained in a 1 1 ratio, (18) indicating that the asymmetric induction from the resident stereocenter is low. 

False Anomers differ in configuration at only the anomeric carbon (Cl). The configurations at the remaining stereocenters (C2 through C5) are the same in a-glucopyranose as they are in /3-glucopyranose. Anomers are therefore diastereomers—not enantiomers—and should not form in equal amounts. Enantiomers differ from each other in configuration at every stereocenter. 

The keto forms of carbohydrates exist in eqnilibrinm with the corresponding five-membered (furanoses) or six-membered (pyranoses) cyclic hemiacetals. The new stereocenter formed by cyclization is called the anomeric carbon, and the two anomers are designated a and /3. 

Mutarotation— the change in the optical rotation that occurs by epimer-ization (i.e., the change in equilibrium between two epimers) when the corresponding stereocenters interconvert. Cyclic sugars show mutarotation as a and P anomeric forms interconvert, changing between the two forms. 

As mentioned above, the stereochemical course of this process is controlled by factors which are completely different from those of a classical glycosylation reaction. In this case two new stereocenters are introduced, at the anomeric position and at C-2, and the stereochemical outcome of the process depends on the config-... 

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