Peter Hamley

Spirocycle assembly through selective tandem ring closing metathesis reactions

Abstract A range of functionalised spirocyclic systems have been prepared under mild and neutral conditions by tandem selective ring closing olefin metathesis reactions. Additionally, a marked preference for 5-membered ring closure over 7-membered ring closure was observed which appears to be a result of a kinetically favoured cyclisation process.

3,4-Dihydro-1-isoquinolinamines: A novel class of nitric oxide synthase inhibitors with a range of isoform selectivity and potency

3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j.

Employment of a cyclobutene ring-opening metathesis reaction towards a concise synthesis of (±)-sporochnol A

Abstract A concise formal synthesis of (±)-sporochnol A 1 , a naturally occurring feeding deterrent towards herbivorous fish, is described. The target compound was prepared by the employment of a Ru-catalysed cyclobutene ring-opening metathesis reaction with gaseous ethylene followed by a site selective hydroboration reaction as the key steps. The optimisation of the metathesis process regarding the Ru-catalyst and reaction conditions is also delineated.

Thienopyridines : Nitric oxide synthase inhibitors with potent in vivo activity

5-Substituted 7-amino-4,5-tetrahydrothieno[2,3-c]pyridines and 6-substituted 4-amino-6,7-dihydrothieno[3,2-c]pyridines were shown to be exceptionally potent inhibitors of inducible and neuronal nitric oxide synthase. Selectivity and potency could be modulated by variation of the 5- or 6-substituent. Compound 3e showed potent in vivo inhibition of iNOS.

The synthesis of 1-aminodihydroisoquinolines by an imine addition-cyclisation reaction

Abstract A variety of 1-amino-3,4-dihydroisoquinolines substituted at the 3-position and related thienopyridines were prepared by lithiation of ortho-methyl aromatic nitriles, addition to N-trimethylsilylimines and spontaneous cyclisation.

Regio- and stereoselective functionalisation of monocyclic medium ring lactams

Abstract The functionalisation of the potassium enolates of a series of racemic 7-, 8-, and 9-membered unsaturated lactams with trisyl azide and phenylselenenyl chloride afforded the corresponding 3, n -disubstituted lactams with good stereoselectivities.

A study of the regioselectivity of oxygen insertion in the Baeyer–Villiger oxidation of bicyclo[2.2.1]heptan-2-ones

Synthesis and Baeyer–Villiger oxidation of the series of bicyclic ketones 3 and 6 is described. The ratio of methine to methylene carbon migration in the oxidation was found to vary depending on the 5-endo and 7-anti substituents of the ketones. Possible reasons for the observed regioselectivity are discussed.

The Discovery of Novel, Potent and Highly Selective Inhibitors of Inducible Nitric Oxide Synthase (Inos).

By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.

The synthesis of angularly fused tricyclic compoundsvia tandem ring closing metathesis reactions

A novel and highly efficient approach to angularly fused tricycles has been developed through the employment of selective tandem ring closing metathesis reactions.