A copper (I)-catalyzed, asymmetric method to directly functionalize pyridines, quinolines, and isoquinolines with terminal alkynes is described. The reaction is readily diversified to incorporate a range of pyridine-based heterocycles and electron-rich or electron-poor alkynes. This provides a straightforward alternative to nucleophilic or cross-coupling approaches to directly derivatize these heterocycles, and yields useful propargylcarbamates.

The identification of potent, highly selective orally bioavailable ghrelin receptor inverse agonists from a spiro-azetidino-piperidine series is described. Examples from this series have promising in vivo pharmacokinetics and increase glucose-stimulated insulin secretion in human whole and dispersed islets. A physicochemistry-based strategy to increase lipophilic efficiency for ghrelin receptor potency and retain low clearance and satisfactory permeability while reducing offtarget pharmacology led to the discovery of 16h. Compound 16h has a superior balance of ghrelin receptor pharmacology and off-target selectivity. On the basis of its promising pharmacological and safety profile, 16h was advanced to human clinical trials.

A new route to form C(sp)-N bonds has been developed via addition of in situ generated lithium acetylides to sterically hindered diazodicarboxylates. The reaction provides straightforward access to a previously unexplored ynehydrazide class of stable N-linked alkynes directly from commercially available precursors. Preliminary results show that alkynyl hydrazides are useful reagents for the selective installation of nitrogen functional groups and as precursors to pharmaceutically relevant heterocycles using metal catalyzed cycloadditions and condensations.

The total syntheses of the highly cytotoxic neo-antimycin macrocyclic depsipeptide natural products kitastatin and respirantin have been accomplished in a convergent manner using MNBA promoted esterifications and an efficient C- and N-terminus bis-deprotection/HATU promoted macrolactamization. The first examples of using a prenyltrifluoroborate reagent in additions to carbonyl groups are disclosed including a diastereoselective multigram scale montmorillonite K10 catalyzed prenylation of N-Boc-l-leucinal to install the structurally unique gem-dimethyl-β-keto-ester fragment.

The syntheses, characterisation and biological activities (IC 50 ; DNA binding) of four mononuclear Pt oxazoline complexes are reported. These materials are the compounds cis-[PtCl) and all four are shown to have slightly lower cytotoxicities in vitro when compared to cisplatin against the A2780 ovarian cancer cell line. These new materials all appear to be bio-active via the formation of DNA adducts. Complexes 1 and 2 have been further characterised in the solid-state by X-ray diffraction methods.