Studies on ring closure heterometathesis and the synthesis of novel glycosidase inhibitors

Compound I was synthesised to study intramolecular ring closing metathesis of an oxime and an olefin. In the event an intermolecular reaction took place to give II. (Fig. 11160A).;A series of bias imines IV were synthesised and also subjected to ring closure metathesis conditions using the Grubbs catalyst. No cyclisation was observed. (Fig. 11160B).;Three diamino sugar derivatives V were prepared by epoxide opening of the corresponding 2,3 manno (up) epoxide. Benzylidene deprotection was not possible. (Fig. 11160C).;A further six examples of deprotected diamino altro derivatives 395b-g were prepared and tested for glycosidase inhibition and the best results were obtained when n = 4 and n = 5 where IC50 values gave 0.15 mM and 0.63 mM respectively for beta-galactosidase from bovine liver. Nine examples of the benzylamino altro derivatives were prepared and tested for glycosidase inhibition. IC50 values obtained gave 70 microM and 90 microM where n = 3, R = H and n = 4, R = H respectively for beta-galactosidase from bovine liver. (Fig. 11160D).;Opening the manno epoxide produced seven examples and the structure of the products were proved with an X-ray structure where R = morpholine. The stereochemistries of the other examples were assigned following 13 C comparison. By contrast opening of the allo epoxide gave attack at C-3 and this fact was determined by an X-ray structure on R = furanyl. 13C comparison indicated that the other examples had followed attack at C-3.