Background: Many polyhydroxylated piperidines are inhibitors of the oligosaccharide processing\ud enzymes, glycosidases and glycosyltransferases. Aza-C-linked disaccharide mimetics are compounds\ud in which saturated polyhydroxylated nitrogen and oxygen heterocycles are linked by an all-carbon\ud tether. The saturated oxygen heterocycle has the potential to mimic the departing sugar in a\ud glycosidase-catalysed reaction and aza-C-linked disaccharide mimetics may, therefore, be more\ud potent inhibitors of these enzymes.\ud \ud \ud Results: The scope, limitations and diastereoselectivity of the dihydroxylation of stereoisomeric\ud 2-butyl-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydro-pyridin-3-ols is discussed. In the absence of a 6-\ud substituent on the piperidine ring, the Upjohn (cat. OsO4, NMO, acetone-water) and Donohoe\ud (OsO4, TMEDA, CH2Cl2) conditions allow complementary diastereoselective functionalisation of\ud the alkene of the (2R*,3R*) diastereoisomer. However, in the presence of a 6-substituent, the\ud reaction is largely controlled by steric effects with both reagents. The most synthetically useful\ud protocols were exploited in the two-directional synthesis of aza-C-linked disaccharide analogues.\ud A two-directional oxidative ring expansion was used to prepare bis-enones such as (2R,6S,2'S)-6-\ud methoxy-2-(6-methoxy-3-oxo-3,6-dihydro-2H-pyran-2-ylmethyl)-1-(toluene-4-sulfonyl)-1,6-\ud dihydro-2H-pyridin-3-one from the corresponding difuran. Selective substitution of its N,O acetal\ud was possible. The stereochemical outcome of a two-directional Luche reduction step was different\ud in the two heterocyclic rings, and depended on the conformation of the ring. Finally, twodirectional\ud diastereoselective dihydroxylation yielded seven different aza-C-linked disaccharide\ud analogues.\ud \ud \ud Conclusion: A two-directional approach may be exploited in the synthesis of aza-C-linked\ud disaccharide mimetics. Unlike previous approaches to similar molecules, neither of the heterocyclic\ud rings is directly derived from a sugar, allowing mimetics with unusual configurations to be prepared.\ud The work demonstrates that highly unsymmetrical molecules may be prepared using a two\ud directional approach. The deprotected compounds may have potential as inhibitors of\ud oligosaccharide-processing enzymes and as tools in chemical genetic investigations
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