Anomeric amides

However, workers do not agree as to the shape of the c.d. spectrum for these sugars at shorter wavelengths, as Fig. 15 demonstrates. The correct spectrum still remains an open question, but the intense c.d. band expected at 190 nm for the amide mr c.d. bands are of opposite sign for the two anomers and nearly cancel in the equilibrium mixture. Thus, differences in the anomeric mixtures could explain differences in the c.d. spectra. The amide irir c.d. band is obvious for the anomeric mixture from 2-acetamido-... 

V-Acetylneuraminic acid is a common group in glycoproteins, and it contains both the amide and carboxyl chromophores. As shown in formula 11, this nine-carbon sugar derivative has an equatorial amido group on C-5 and both a hydroxyl group and a carboxyl group on the anomeric carbon atom. 

This review will cover the structural, physical, spectroscopic, chemical and biological properties of the most widely studied class of these anomeric amides, the A-acyloxy-A-alkoxyamides 3. 

These not only exhibit all the structural and spectroscopic characteristics of anomeric amides 2, their reactivity patterns embrace a range of reactions at the amide nitrogen that in many respects parallel those at a saturated carbon.37 46 In addition, they are mutagenic as well as DNA damaging agents that have anticancer capability.37,38,40,46 50 To date nearly a hundred of these have been synthesised in our laboratory while, recently, a range of urea and urethane analogues have also been reported.51 53... 

These results clearly indicate that barriers to all isomerisation processes are at least less than about 8kcalmol 1. In /V-benzyloxy-7V-chlorobenzamide 44 the amide isomerisation was not observable but the anomeric overlap resulted in diastereotopic benzylic hydrogens, which at coalescence afforded a barrier for rotation about the N-OBn bond of around 10.3 kcalmol-1.32 Like its /V-chloro analogue, the amide isomerisation barrier in 43 is too low to be observed by 3H NMR and even though there is definitive X-ray and theoretical evidence for anomeric effects in /V-acyloxy-/Y-alkoxyamidcs, the barrier to isomerisation about the N-OBn bond must be lower than 10.3 kcalmol-1. The n0-CN ci anomeric interaction in 44 is predicted to be stronger than the n0-CN OAc interaction in 43 on purturbation arguments.32... 

Ar-Acyl oxy- A -a 1 k oxyamides have been found to undergo SN2 reactions with a number of organic and inorganic nucleophiles including anilines, thiols, hydroxide and azide anions. Reaction products from all of these processes are themselves reactive anomeric amides and outcomes have uncovered novel chemistry of this unusual class of compounds. 

The Ea for azide reaction on A-formyloxy-A-m< //n7formamide was 22.2 kcal mol-1 higher than reaction with the A-methoxy model. A similar result was obtained to the reactions of ammonia and reinforces the activating influence of /V-alkoxy groups upon SN2 reactions in anomeric A-acyloxy-A-alkoxy amides. 

The need for electrophilicity at the amide nitrogen was demonstrated by comparison of the mutagenic activity of 28a with that of two analogues with similar structure, A-benzoyloxy-A-benzylbenzamide 117, which possesses a leaving group but without anomeric destabilisation and A-benzyl-A-benzyloxybenzamide 118,... 

Y-Acyloxy-Ar-alkoxyamidcs are a class of biologically active amides, which are members of the recently identified class we have termed anomeric amides. These are... 

The physical and spectroscopic properties of /V-acyloxy-A-alkoxyamides confirm pyramidality at nitrogen and the disconnection of the nitrogen lone pair from the amide carbonyl. The presence of an acyloxyl and an alkoxyl group at nitrogen also results in an anomeric interaction between the oxygens, which is facilitated by the sp3-hybridised nitrogen. Experimental observations, including X-ray analysis are fully supported by results from computational chemistry. 

Aminoacridine carboxamide derivatives binding with DNA, 194, 195 Anomeric amides, 37, see also A-acyloxy-A-alkoxyamides... 

While the term anomeric amides may be used to describe all systems bearing two heteroatoms at nitrogen and thus capable of displaying anomeric effects, not all properties exhibited by these amides may be attributed solely to the operation of such effects . 

This chapter will cover the synthesis, structure and chemical reactivity of various N-heteroatom-substituted hydroxamic esters, anomeric amides in which at least one of the heteroatom substituents at nitrogen is an alkoxyl group. Throughout this review, these will either be referred to as A-substituted hydroxamic esters or as A-substituted-A-alkoxy amides. 

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