Exploiting a novel size exclusion phenomenon for enantioselective acid/base cascade catalysis.

A novel size exclusion phenomenon between PS-BEMP and sterically bulky BPAs, has been discovered and exploited in a one-pot base-catalysed Michael addition/acid-catalysed enantioselective N-acyliminium cyclisation cascade, allowing the preparation of structurally complex β-carbolines with moderate to good enantiocontrol.

Enantioselective Brønsted acid-catalyzed N-acyliminium cyclization cascades.

An enantioselective Brønsted acid-catalyzed N-acyliminium cyclization cascade of tryptamines with enol lactones to form architecturally complex heterocycles in high enantiomeric excess has been developed. The reaction is technically simple to perform as well as atom-efficient and may be coupled to a gold(I)-catalyzed cycloisomerization of alkynoic acids whereby the key enol lactone reaction partner is generated in situ. Employing up to 10 mol % bulky chiral phosphoric acid catalysts in boiling toluene allowed the product materials to be generated in good overall yields (63-99%) and high enantioselectivities (72-99% ee).

Synthesis and biological characterisation of novel N-alkyl-deoxynojirimycin alpha-glucosidase inhibitors.

The N-alkylated deoxynojirimycin compound, N-(6'-(4''-azido-2''-nitrophenylamino)hexyl)-1-deoxynojirimycin (6) was synthesised as a potential photoaffinity probe for endoplasmic reticulum (ER) alpha-glucosidases I and II. Surprisingly this compound was a highly potent inhibitor of alpha-glucosidase I (IC(50), 17 nM) in an in vitro assay and proved equally effective at inhibiting cellular ER glucosidases, as determined by a free oligosaccharide (FOS) analysis. A modest library of compounds was synthesised to obtain structure-activity information by variation of the N-alkyl chain length and modifications to the azido-nitrophenyl group.

Site isolated base and acid catalyzed azaspirocyclization cascades.

A one-pot, site isolated base (PS-BEMP) and acid (Si-TsOH) catalyzed cyclization cascade to azaspirocyclic molecules is reported; the reaction is simple to perform, atom efficient (water is the only byproduct) and broad in its scope to a diverse range of azaspirocyclic products.

Highly stereoselective oxy-michael additions to beta,gamma-unsaturated alpha-keto esters: rapid enantioselective synthesis of 3-hydroxybutenolides.

The highly diastereoselective oxy-Michael addition of the "naked" anion of (6S)-methyl delta-lactol to gamma-substituted beta,gamma-unsaturated alpha-keto esters leading to the direct formation of THP*-protected gamma-hydroxy alpha-keto ester derivatives is described. Subsequent acid-mediated deprotection affords the 3-hydroxybutenolides in high yields.