Certain Sugar Derivatives

Mutarotation of Certain Sugar Derivatives 1. Anomerization by Way of a Cyclic Carbonium Ion 

This process is the main course for the acid-catalyzed anomerization of sugar acetates, methyl glycosides, and related compounds in non-aqueous solvents.104,244,245 260,263 In many instances, formation of the cyclic carbonium ion is assisted by participation of a neighboring acetyl group,104 but this process is not a necessary feature. Anomerization of tetra-O-acetyl-2-deoxy-a-D-arafomo-hexopyranose takes place through a cyclic carbonium ion as depicted.245 b) 

The cyclic and the acyclic mechanisms differ fundamentally. In the cyclic mechanism, the acid catalyst attacks the anomeric oxygen atom, and electrons move from the anomeric carbon atom to the 

Several comprehensive studies have been made of the anomeriza-tion and isomerization reactions of methyl glycosides under a wide variety of conditions, and the reaction rates have been correlated with configurations and conformations. The work is not discussed here, because it has been covered in several excellent reviews.100,264-267 

This type of reaction may be illustrated by the reaction of tetra-O-acetyl-a-D-glucopyranosyl bromide in acetonitrile with silver fluoride, to give tetra-0-acetyI-/3-D-glucopyranosyl fluoride.268,269 Application of a similar process to the anomerization of a free sugar in water would 

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Iodo-desoxy derivatives of methylene, benzylidene and isopropylidene compounds have been transformed into their desoxy analogues with Raney nickel and hydrogen in basic media (e.g. hydroxides, methoxides and diethylamine). 0 47,60,81,82 Under similar conditions, l,3 2,4-diben-zylidene-5,6-sorbitoleen has been hydrogenated 8 and 2,4-benzylidene-6-nitro-6-desoxy-D-sorbitol has been converted into the corresponding amine.84 We are not aware of any report in this field of the removal of a benzylidene group by Raney nickel, as is the case with certain sugar derivatives.88... 

Alumina " is an excellent adsorbent for the chromatography of certain sugar derivatives. It sharply differentiates between anomers, yielding crystalline substances from both sirupy and crystalline mixtures. Frequently, the 13-d anomer moves down the adsorbent column more rapidly than does the a-n form 1,2,4-tri-0-acetyl-6-deoxy-3-0-methyl-d-D-glu-... 

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]. 

An attractive feature in this reaction is the possibility of direct substitution and formation of unblocked sugar derivatives containing one or more chlorodeoxy function in essentially two steps. Another facet is the formation of methyl 4,6-dichloro-4,6-dideoxy-hexosides from certain methyl glycosides in one step. Such compounds could be valuable intermediates in the synthesis of dideoxy and diamino sugars of biological importance. 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

In contrast with the usual complete methylation, a selective methyla-tion of certain hydroxyl groups has been accomplished by direct reaction (as differing from methods requiring blocking groups and their subsequent removal) in a limited number of cases. Monomeric sugar derivatives will be considered first, to be followed by polysaccharides, since with the latter there are factors involved which introduce complications. 

Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. Furthermore, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. For example, the unnatural L-nucleoside 1 inhibits reverse transcriptase and shows potent and selective anti-AIDS activity,1 and the unsaturated neuraminic acid analogue 2 is the sialidase-inhibitory... 

R. E. Arrick, D. C. Baker, and D. Horton, Chromium trioxide-dipyridine complex as an oxidant for partially protected sugar preparation of aldehydo and certain keto sugar derivatives, Carbohydr. Res., 26 (1973) 441 147. 

Besides such utilization, certain studies9(e),(d),17,21,24,29(c) have been dedicated to a systematic examination of the reactivity of sugar derivatives and phosphoranes at qualitative and even semi-quantitative21 levels. 

In comparison to some of the other activation methods however, the dimethyl sulfoxide-acetic anhydride procedure has certain disadvantages. The method often requires the use of long reaction times (1 24 h), which can result in many side reactions, especially with sensitive substrates. Notable in this respect is that it is not uncommon for this procedure to result in the formation of substantial yields of the thiomethyl ethers obtained from the Pummerer rearrangement product as described above. In fact upon attempted oxidation of cholesterol with this system, the major product obtained was the corresponding (methylthio)methyl ether. Acetates may also be formed if the alcohol is unhindered. For example the sugar derivative (9) reacts under these conditions to form an enol acetate (derived from the requir carbonyl compound) in 40% yield contaminated with 30% of the acetate (10 equation S). ... 

All of these experiments strongly indicate that the alkaline hydrolysis of the sugar orthoacetates is a nucleophilic displacement reaction. Any one of the three carbon atoms of the five-membered ring may be attacked. Since the hydroxyl ion must approach the tetrahedron of the attacked carbon atom in the direction of the center of the face opposite the vertex occupied by the group to be displaced, it is evident that the reaction must be accompanied by the inversion of configuration of the attacked carbon atom. It is quite certain that the attack does not take place on carbon atom 2, because in such a case the reaction product would be the epimeric sugar derivative. Therefore, either carbon atom 1 or the central carbon atom of the orthoester group is attacked. In the first case, the reaction is as follows. 

NA hen Harries (2) at the beginning of the present century carried out his fundamental experiments with a view to ozonizing organic compounds, he also studied the effect of ozone on certain sugar alcohols. His initial studies showed that the primary alcoholic hydroxyls of sugar derivatives can be oxidized to form aldehyde groups by utilizing ozone. 

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