Imino sugars protonation

The bioactivity of imino sugars is due to the fact that they inhibit glycosidases. Once protonated, the imino sugar mime the oxonium ion intermediate of the reaction catalysed by those enzymes (Fig. 32), and therefore binds the active site. 

Fig. 20.6. Possible stabilization of the A C base pair as seen in the crystal structure of d(CGCGAATTAGCG) by protonation of adenine (left) is more probable than the amino-imino tautomerism (right). Atom designation as in Fig. 20.4 R = sugar residue...

A striking feature in the reactions of osazones is the fact that the two hydrazone residues are nonidentical in their reactivity. The hydrazone residue at C-1 is readily alkylated and acylated, but that at C-2 is not. This behavior has been attributed to chelation of the imino proton of the hydrazone at C-2. Furthermore, among the hydroxyl groups of the sugar residue, the one on C-3 seems to be very reactive, readily undergoing dehydration and, in some cases, inversion this is followed in reactivity by the primary hydroxyl group (on C-6 of hexoses), which readily engages in the formation of 3,6-anhydrides. 

The numbering of atoms within the base and sugar moieties is according to the standard lUPAC/IUB rules [84S1]. The resonance positions of the imino protons incorporated in this survey are all based on one and/or two dimensional nuclear Overhauser enhancement spectroscopy. 

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