2-amino-2-deoxyaldoses

The nib o-aldol reaction using l,l-diethoxy-2-nib oethane is useful for lengthening of the carbon chain of carbohydrates. The reaction of Eq. 3.86 proceeds in a stereoselective way (ds 75%) to give the syn-niho alcohol in 58% isolated yield.The product is converted into 2-amino-2-deoxyaldoses by reaction with Ha/Raney Ni. 

Keywords Acetylacetates, 2-Amino-2-deoxyaldoses, Barbituric acids, C-Glyco-sides, Dimedone, Furans, Garcia-Gonzalez reaction, Green chemistry, Hexoses, Meldrum s acid, Penta-2,4-dione, Pentoses, Pyrroles, Reactions in water, Tetrahy-drofuranylfurans... 

Another class of pyrrole derivative may be obtained by the interaction of l-amino-l-deoxy-2-ketoses or 2-amino-2-deoxyaldoses with a jQ-dicarbonyl compound. Unlike the previous type (which is N-substituted), these pyrrole derivatives have a tetrahydroxybutyl group in the a- or /8-position with respect to the nitrogen atom of the ring, in addition to other groups arising from the dicarbonyl compound used in the condensation. The formation and reactions of this type of pyrrole derivative have been discussed in detail in two articles in this series48,49 they will, therefore, only be treated briefly. 1-Amino-l-deoxy-D-fructose (53) reacts with 2,4-pentanedione to give50 pyrrole derivative 54a similar pyrroles were obtained with ethyl acetoace-tate,50,51 which yields 54b. 

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

Acyclic carbohydrate derivatives containing unsaturation, with some exceptions, exhibit much of the chemistry already described for cyclic analogues, and their usefulness should not be overlooked. Unsaturated derivatives of alditols can be made, for example, by standard eliminations from alditol v/r-disulfonates or epoxides or by /f-eliminations from O-substituted 1-deoxy-l-nitroalditols and 1-deoxy-l-sulfonylalditols. Additions of hydrogen and ammonia to the unsaturated nitroalditols made in this way offer, respectively, routes to 2-deoxy- and 2-amino-2-deoxyaldoses.255... 

Direct alkaline epimerization of the 2-amino-2-deoxyaldoses may become a useful reaction, since a ketose cannot be formed.38 ... 

Ketoses undergo a similar series of reactions, leading to 2-amino-2-deoxyaldoses (Heyns rearrangement). However, browning reactions of fructose differ from those of glucose, e.g., loss of amino acid or of free amino groups (casein) is much lower.28... 

In 1937, the true structure of the rearranged product was reported by Kuhn and Weygand. Amadori s stable isomers were shown to be unbranched A-substituted l-amino-l-deoxy-2-ketoses. Therefore, in a strict sense, the reaction named by Kuhn and Weygand the Amadori rearrangement is the complete conversion of a Af-substituted aldosylamine to a iV-substituted l-amino-l-deoxy-2-ketose. On this basis, simple enolization of an aldosylamine or ketosylamine to the intermediate 1,2-enolic form common to both should not be construed as the Amadori rearrangement. Also, the recently demonstrated conversion of a ketosylamine to a 2-amino-2-deoxyaldose does not come under the definition in spite of an obvious similarity to the Amadori rearrangement. 

A modification of the Kiliani-Fischer method for amino functionality introduction involves the condensation of free sugars with arylamines to give imines, which are treated directly with hydrogen cyanide to produce aminonitriles. Hydrogenolysis and hydrolysis of the resulting aminonitriles gives 2-amino-2-deoxyaldoses with one carbon extended [103],... 

Products of considerable potential interest for the synthesis of 2-amino-2-deoxyaldose derivatives have been obtained by the addition of nitrosyl chloride to acetylated glycals. Tri-O-acetyl-n-glucal and di-O-acetyl-n-arabinal react smoothly in carbon tetrachloride at 0° to give crystalline products which, on the basis of their chemical reactivities and their nuclear magnetic resonance spectra, have been assigned the structures of tri-0-acetyl-2-deoxy-2-nitroso-Q -D-glucopyranosyl chloride (32) and di-O-acetyl-2-deoxy-2-nitroso-j3-n-arabinopyranosyl chloride (33). It was not estab-... 

The reactions of 2-amino-2-deoxyaldoses and 1-amino-l-deoxyketoses, and their A-alkyl and A -aryl derivatives, with /3-dicarbonyl compounds give pyrrole derivatives whose nature depends somewhat upon the experimental conditions used. Accounts of these reactions, and discussions of the structures and properties of the products, are given in this Section. The mechanisms are dealt with in Section IV. 

On comparing the reactions of 2-amino-2-deoxyaldoses and 1-amino-l-deoxyketoses with 8-dicarbonyl compounds, which yield pyrroles (Scheme A, X = NH, A -alkyl, or A -aryl), with the reactions of the nonnitrogenous aldoses and ketoses with the same compounds, which yield furan derivatives (Scheme A, X = 0), it may be noted that the changes of bonds are the same. It seems reasonable, therefore, to assume that both processes proceed through the same, or at least similar, mechanisms. From the experimental point of view, the main differences between these two reactions concern rates and catalysts. Aldoses and ketoses react very slowly in the absence of such acidic catalysts as zinc chloride and ferric chloride. The reactions of the amino sugars are much faster and are usually performed under neutral or slightly basic conditions. 

Amino-2-deoxyaldohexoses, 1-amino-l-deoxyketohexoses, and their V-alkyl and JV-aryl derivatives react with /3-dicarbonyl compounds, giving substituted (tetrahydroxybutyl)pyrroles. It is, most probably, a general reaction of 2-amino-2-deoxyaldoses and 1-amino-l-deoxyketoses which parallels the formation of (polyhydroxyalkyl)furans from nonnitrogenous monosaccharides. In the reactions with amino sugars in alkaline media, simpler pyrrole compounds lacking the tetrahydroxybutyl chain are also obtained. 

Glycosyl isothiocyanates have also been allowed to react with unprotected 2-amino-2-deoxyaldoses and 1-amino-1-deoxy-2-ketoses.68 This reaction leads to the formation of heterocyclic derivatives resulting from cy-clization involving the carbonyl group of the amino sugar moiety following the mechanistic pathway already discussed for similar condensation reactions with alkyl and aryl isothiocaynates. 

The reaction between 2-amino-2-deoxyaldose (204) and cyclic /8-dicarbonyl compounds such as 205 or acyclic ones yielded polyhydroxyalkylpyrroles 206 and 207, respectively [74AQ1082 80MI1 87AQ(C)271],... 

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