Nitrous Acid Deamination of Amino Sugars

Nitrous acid deamination of simple aliphatic primary amines involves, according to Ingold and coworkers, an intermediate diazonium ion  

Whitmore and Langlois have shown that the deamination of butylamine in the presence of chloride ion provides butenes, 1-butanol, and 2-butanol as the major products, and 1-chlorobutane and 2-chlorobutane as minor products. The formation of these compounds was explained on the basis of an intermediate, carbonium ion. 

The above mechanisms provide a basis for rationalizing the nitrous acid deamination of amino sugars, a reaction which yields a variety of products and often proceeds with the formation of a new ring-structure. Many of these reactions are profoundly affected by the nature of the neighboring group and by the configuration and conformation of the molecule. 

Structure Configuration Conformation Group antiparallel to N Expected Product 

Certain aspects of the above reaction, particularly the ingenious and unique method employed by Levene and LaForge for deducing the configuration of 2,5-anhydro-n-mannose, chitose, from the properties 

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The chemistry of the 2,5-anhydrides of aldoses subsequently entered a prolonged lull, and Peat s review21 of 1946 in this Series does not report on any work later than 1925. The experimental basis of the deamination of amino sugars with nitrous acid was, nevertheless, established. The progress afterwards made in the conformational analysis of sugars made it possible for Shafizadeh22 to draw a parallel with the nitrous acid deamination of the aminocyclohexanols, and to rationalize the whole of these results. 

A sensitive fluorimetric assay for 2-amino-2-deoxy-D-hexoses with increased sensitivity over the Elson-Morgan and Dische-Borenfreund indole methods has been reported. The 2,5-anhydrohexoses produced by nitrous acid deamination of heparin, heparan sulphate, and 2-amino-2-deoxy-D-hexoses have been treated with 3,5-diaminobenzoic acid to give stable derivatives. Neither neutral sugars nor acetamido sugars interfere in the reaction. In a modification of an earlier procedure, equivalent colour complexes were formed by the interaction of 3-methyl 2-benzothiazoline and the 2,5-anhydrohexoses produced by deamination of 2-amino-2-deoxy-D-glucose and 2-amino-2-deoxy-D-galactose. ... 

Application of nitrous acid deamination to the naturally occurring chitosamine 45) (2-amino-2-deoxy-D-glucose) provided Fischer and Tie-mann 46) with the first recorded example of a hydrofuran anhydro sugar. The sirupy product, chitose, could be oxidized to give, successively, an... 

More-specific methods are available for identifying and quantitating the typical, amino sugar component of heparin (and some heparan sulfate species), namely, 2-deoxy-2-sulfoamino-D-glucose. Most of these methods are based on conversion of these residues into 2,5-anhydro-D-mannose by deamination with nitrous acid (see Section VIII,2). The 2,5-anhydro-D-mannose residues may be determined either colorimetrically,52-54 or fluorimetrically.55... 

Undoubtedly, the vicinal groups play a fundamental role in the outcome of this reaction, especially with the sugars, where the favored conformation of the molecule at equilibrium is controlled at the outset by groups that determine whether the molecule exists as a cyclic or acyclic structure. The deamination of cyclic and acyclic amino sugar derivatives by nitrous acid will be considered in turn. 

Anhydro-adenosine has been isomerized to 2, 3-anhydro-jS-D-lyxo-furanosyl-adenine in 42% overall yield by the sequence outlined in Scheme 8. Deamination of l-(3-amino-3-deoxy-j3-D-xylofuranosyl)-uracil with nitrous acid did not yield any 2, 3 -anhydro-uridine or products derived from this anhydro-sugar derivative, uracil being the major product. ... 

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