Anomeric stereochemistry

A double mutant (acid/base and nucleophile) Abg E71A E358G was developed58 which efficiently catalyzes thioglycoside formation from a glycosyl fluoridine donor (69) with inverted anomeric stereochemistry. This represents a significant improvement, as glycosyl fluoride donors are much more accessible (Fig. 29). 

A parameter that has been useful for defining the anomeric stereochemistry of glycopyranosides is the chemical shift of the anomeric carbon atom, C-l. Similarly, the 13C NMR shifts of C-l in methyl septanosides also diagnostic for their anomeric configuration. In general, the Sc.i values for a-septanosides are slightly upfield (99-104 ppm in completely deprotected septanosides) relative to (S-septanosides (104-111 ppm) (Table I). This distribution of chemical shifts mirrors the trends for pyranosides namely, the C-l chemical shifts for a-pyranosides lie upfield from those of p-pyranosides. This observation suggests that the anomeric effect is operative in... 

A. Kittaka, T. Asakura, T. Kuze, H. Tanaka, N. Yamada, K. T. Nakamura, and T. Miyasaka, Cyclization reactions of nucleoside anomeric radical with olefin tethered on base Factors that induce anomeric stereochemistry,/. Org. Chem., 64 (1999) 7081-7093. 

Intramolecular radical cyclization followed by trapping of the intermediate with an enone has been investigated by Fraser-Reid and co-workers [95JOC3871] as a method for the synthesis of highly functionalized C-glycosyl derivatives. The control of the anomeric stereochemistry as well as the facial selectivity in the addition to the chiral enone is impressive. 

Unlike the other N5 modifications described previously, a 5-azido thioglycoside was found to be less reactive than the simple amide as is clear from the measured relative reactivity values (RRVs) (Fig. 5.4) [59], However, it was subsequently reported by Teruaki Mukaiyama and coworkers that a 5-azido sialyl fluoride was more reactive than both the corresponding acetamide and the V,V-diacctyl derivatives toward activation with the combination of SnCl4 and AgB(C6F5)4, although this may be a consequence of the differing anomeric stereochemistries employed [60],... 

In 1981, Acton et al. [143] performed the reaction shown in Scheme 7.41, to give a 3 1 ratio of anomeric esters. Shortly thereafter, Nicotra et al. [144] ran a similar reaction and studied the chemical shifts of the resulting a and (3 anomers. This study yielded an easy method for the assignment of the anomeric stereochemistry, with the anomeric carbon of the a anomer possessing a chemical shift of approximately 33 ppm and that of the (3 anomer possessing a chemical shift of approximately 37 ppm. 

Preliminary to a second-generation synthesis of the 3-(9-methyl-y-( 1 -4)-mannans, Kishi and co-workers screened a series of mannosyl phosphates for the influence of the 0-2 protecting group and the anomeric stereochemistry of the donor on the outcome of the glycosylation reaction. As may be seen from Scheme 26, the use of benzyl ether protection under these homogeneous solution-phase conditions gave selectivities that were insufficient, whereas the 2-benzoates gave exquisite a-selectivity.34... 

SCHEME 26. Influence of the O-2-protecting group and anomeric stereochemistry on glycosylation. 

The transient anomeric lithiation shown in Scheme 3.2.1 differs from standard halogen-metal exchanges in that a reductive mechanism is involved. The use of reductive methods, illustrated in Figure 3.2.2, is complimentary to the exploitation of metal exchange reactions for the formation of glycosidic nucleophiles in that strategies towards selectivity in the anomeric stereochemistry become available. 

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. 

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. 

Of equal significance is the ability to control the anomeric stereochemistry. Isomerisation can be initiated by protection of the alkyne as the dicobalthex-acarbonyl complex (51) subsequent epimerisation with catalytic amounts of triflic acid affords the P-anomer (52). 

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