Epoxyalkyl glycosides

In the classic studies by Sharon et al. [12] and Legler and Bause [13], epoxyalkyl glycosides were used to inhibit the action of various glycan hydrolases. In view of the almost certain presence of an acid residue at the active site and the two mechanisms which have been proposed for the action of glycan hydrolases, namely that involving hydrolysis with retention or inversion of configuration at the anomeric centre (Figs. 1 and 2) [14, 15], we decided to use epoxyalkyl... 

Chitin is an abundant biopolymer, especially in Perth where the thriving Western rock lobster industry produces tonnes of waste, a good proportion of which is exoskeleton and rich in chitin. It has been our aim for some years to put this waste chitin to some good use and so, initially, we have set out to prepare epoxyalkyl glycosides based on W-acetyl-D-glucosamine and its oligomers, for example 60 and 61. It is hoped that molecules such as 60 and 61 will prove to be efficient inhibitors of chitinases, ubiquitous enzymes involved in many biological processes [42]. 

Our initial aim was to prepare the epoxyalkyl glycosides 60 as mixtures of dia-stereoisomers. The literature abounds with methods for such syntheses, ranging from Lewis-acid mediated condensations of the acetate 62 [43,44] to acid-catalyzed additions to the oxazoline 63 [45,46]. All of these transformations seemed rather cumbersome and long-winded to us, especially those involving the separate preparation of the oxazoline ... 

X-ray crystallography and NMR spectroscopy are both powerful tools for the investigation of protein structure and conformation. Vital information may be obtained about the binding sites and catalytic sites of enzymes, particularly if the enzyme can be crystallized with the natural substrate or some smaller, analogue molecule in place at the active site. It occurred to us that our epoxyalkyl glycosides, suitably modified to contain either an iodine (heavy) or fluorine (magnetically active) atom, would be ideal molecules to assist in X-ray crystallographic and NMR analyses, respectively. 

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