Carbohydrate chemistry isomerization

R. U. Lemieux, Reamangements and isomerization in carbohydrate chemistry. Molecular Rearrangements, Part II (P. de Mayo, ed.). Wiley-Intersdence, New York, 1963, p. 723. 

Rearrangements and Isomerizations in Carbohydrate Chemistry, R. U. Lemieux, In Molecular Rearrangements, P. de Mayo (Ed.) Interscience Publishers (1964) p. 709. 

In 1913, Emil Fischer and K. Zach1 discovered a new class of sugar derivatives, the glycals, which have become very important in carbohydrate chemistry because of their unusual reactivity and their ease of transformation and isomerization. After the death of Fischer, the subsequent developments in this field were primarily due to M. Bergmann and his associates, particularly H. Schotte. 

The problem of determining the structure of a polysaccharide is similar to that of determining the amino acid sequence of a protein, but it is complicated by the additional structural features unique to carbohydrates branching and linkage isomerism. The elements of carbohydrate chemistry discussed in following paragraphs are those relevant to the problems of determination of carbohydrate composition and the structure of polysaccharides. 

Carbohydrate chemistry provides many examples of reactions that could proceed by alternative pathways, to afford isomeric products that differ in configuration or structure. The effect of the configuration of the reactants on the course of such reactions may depend very largely on whether the reactions are reversible or irreversible. 

Lemieux, R. U. Rearrangements and isomerizations in carbohydrate chemistry. Mol. Rearrangements (Paul de Mayo, editor. Interscience) 1964, 2, 709-769. 

The first example of methoxyl participation reported in carbohydrate chemistry was the migration454 of a methoxyl group from C-l to C-4 during an attempted benzoate displacement reaction with 2,3,5-tri-O-benzyl-4-O-p-tolylsulfonyl-D-ribose dimethyl acetal (185). Instead of the 4-O-benzoyl-L-lyxose derivative expected, the isomeric l-0-benzoyl-2,3,5-tri-0-benzyl-4-0-methyl-L-lyxose methyl hemi-acetal (187) was obtained, presumably by way of the cyclic, oxonium ion 186. Solvolysis of the related aldehydo sugar, namely, 2,3,5-tri-O-benzyl-4-O-p-tolylsulfonyl-D-ribose, readily gives 2,3,5-tri-O-benzyl-L-lyxofuranose, and the reaction probably involves participation by the free aldehyde group.455... 

The y -0-mannopyranoside linkage is traditionally one of the most challenging anomeric linkages to form in carbohydrate chemistry. One popular solution to this problem has been to generate an equatorial radical and allow it to isomerize to its more stable axial position prior to quenching. 

Lemieux RU (1964) Rearrangements and isomerizations in carbohydrate chemistry. In de Mayo P (ed) Molecular rearrangements, Part two. Interscience, New York, pp 709-769... 

Regioselective, partial protection is an important transformation in carbohydrate chemistry as it simplifies preparation of differentially substituted synthetic intermediates. One such procedure is the synthesis of tetraacetyl glucose 2. The method for obtaining 2 was originally presented by Helferich and Zimer and involved a multi-step reaction that eventually led to a mixture of hemiacetal (1-OH derivative) and 2, from which the latter could be isolated in pure form by crystallization in a modest yield of 27%. Chromatographic purification of the material in the mother liquor is impractical due to the propensity of 2 to rapidly isomerize into its more stable hemiacetal counterpart. Since 2 is an important building block, the original protocol is still in frequent use. 

Such a prototropic isomerization has also been applied in an original method for protecting hydroxy groups in carbohydrate chemistry. 

Stereochemistry is the chemistry of molecules in three dimensions. A clear understanding of stereochemistry is crucial for the study of complex molecules that are biologically important, e.g. proteins, carbohydrates and nucleic acids, and also drug molecules, especially in relation to their behaviour and pharmacological actions. Before we go into further detail, let us have a look at different types of isomerism that may exist in organic molecules. 

MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain McKILLOP Advanced Problems in Organic Reaction Mechanisms OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries OSBORN Best Synthetic Methods - Carbohydrates PELLETIER Alkaloids Chemical and Biological Perspectives SESSLER WEGHORN Expanded Contracted and Isomeric Porphyrins WONG WHITESIDES Enzymes in Synthetic Organic Chemistry... 

OSBORN Best Synthetic Methods - Carbohydrates PELLETIER Alkaloids Chemical and Biological Perspectives SESSLER WEGHORN Expanded Contracted and Isomeric Porphyrins WONG WHITESIDES Enzymes in Synthetic Organic Chemistry... 

The hexahydroxycyclohexanes have long been of particular interest to those concerned with the carbohydrates. Originally this interest arose from the fact that they are isomeric with the hexoses and resemble the sugars in water solubility and sweetness it has been sustained by their unique properties, their stereochemical relationships and, finally, by the tantalizing question of their significance in nature. The present review will deal chiefly with the chemistry and configurations of the hexahydroxycyclohexanes or inositols, as they are frequently called, and will touch on certain other closely related polyhydroxycarbocyclic substances. The convenient term cyclitol has come to denote the type of compound that will be considered herein. 

The pr e-Woodwardhn era largely concerned itself with the collection and classification of synthetic tools chemical reactions suited to broad application to the constitutional construction of molecular skeletons (including Kiliani s chain-extension of aldoses, reactions of the aldol type, and cycloadditions of the Diels-Alder type). The pre- Woodwardian era is dominated by two synthetic chemists Emil Fischer and Robert Robinson. Emil Fischer was emphasizing the importance of synthetic chemistry in biology as early as 1907 [30]. He was probably the first to make productive use of the three-dimensional structures of organic molecules, in the interpretation of isomerism phenomena in carbohydrates with the aid of the Van t Hoff and Le Bel tetrahedron model (cf. family tree of aldoses in Scheme 1-6), and in the explanation of the action of an enzyme on a substrate, which assumes that the complementarily fitting surfaces of the mutually dependent partners are noncovalently bound for a little while to one another (shape complementarity) [31],... 

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