Bicycloheptanes as meta-Substituted Arene Bioisosteres

Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates.

Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predict...

Arene substituted cyclopentadienyl complexes of Zr and Hf: preparation and evaluation as catalysts for ethylene trimerisation.

A range of Zr(IV) and Hf(IV) complexes of arene-substituted cyclopentadienyl ligands have been prepared and tested in ethylene oligomerisation. The complexes prepared were designed to be precatalysts to active species which have been predicted, through theoretical studies, to lead to selective ethylene trimerisation. While there is evidence for selective 1-hexene formation in the liquid fractio...

Arene ruthenium complexes as anticancer agents.

Neutral or cationic arene ruthenium complexes providing both hydrophilic as well as hydrophobic properties due to the robustness of the ruthenium-arene unit hold a high potential for the development of metal-based anticancer drugs. Mononuclear arene ruthenium complexes containing P- or N-donor ligands or N,N-, N,O- or O,O-chelating ligands, dinuclear arene ruthenium systems with adjustable orga...

Application of Bioisosteres in Drug Design

Design and synthesis of isoxazole containing bioisosteres of epibatidine as potent nicotinic acetylcholine receptor agonists.

An efficient synthesis of isoxazole containing isosteres of epibatidine is described. The synthesis proceeded from N-tert-butoxycarbonyl (Boc)-exo-2-(methoxycarbonyl)-7-azabicyclo[2.2.1]heptane (9). Compound 9 was reacted with the dilithium salt of an appropriately substituted oxime in tetrahydrofuran (THF). Cyclodehydration of the resultant beta-keto oxime and deprotection of the N-Boc group i...