Organic Synthesis and Catalysis Dr Mal McLeod

Current research activities

Total synthesis of biologically active natural products and analogues

We are developing efficient strategies for the synthesis of natural products with important biological activity. Targets include the microsclerodermin family of antifungal cyclic peptides. These marine natural products hold promise for the treatment of drug resistant pathogenic fungal infections that are a major problem for the growing number of AIDS and organ transplant patients who have compromised immune systems. We are also targeting analogues of the alkaloid methyllycaconitine to elucidate their mode of action as neuronal nicotinic acetylcholine receptor antagonists.

Developing new catalyst for efficient synthesis

Catalysis is a key tenet of modern synthesis. It allows for the efficient, atom economic and scalable conversion of starting materials to products, often with high levels of absolute or relative stereocontrol. We are investigating the development of catalytic asymmetric aminohydroxylation reactions for the synthesis of amino alcohol building blocks with high selectivity; and the development of genetically engineered enzymes for the synthesis of drug metabolites with application to sports drug testing, the detection of residues in agricultural products and pharmaceutical science.

The chemistry of drugs in sport

This project is conducted in close collaboration with the Australian Racing Forensic Laboratories located in Randwick, NSW, and aims to develop new methods for illicit drug detection in thoroughbred, harness and greyhound racing. The project is currently focused on two main areas: the development of high throughput immunoassays for the rapid preliminary screening of race day samples; and the chemical synthesis of phase I and phase II drug metabolites to elucidate metabolic pathways and extend the available methods to detect doping.

Group members

Academic Staff:
Dr Mal McLeod (Leader)

PhD Students:
Belinda Lu   |   Rhiannon Stewart

Honours students:
Dwain Hoskins

Visiting Scholars:
Jill Halliday   |   Shane Wilkinson

Key publications

1. Shuter, E. C.; Duong, H.; Hutton, C. A.; McLeod, M. D. The enantioselective synthesis of APTO and AETD: polyhydroxylated Β-amino acid constituents of the microsclerodermin cyclic peptides. Org. Biomol. Chem., 2007, 5, 3183-3189. DOI: 10.1039/b707891a
2. Halliday, J. I.; Chebib, M.; Turner, P.; McLeod, M. D., Double-Mannich annulation of cyclic ketones using N,N-bis(ethoxymethyl)alkylamine reagents. Org. Lett. 2006, 8, 3399-3401. DOI: 10.1021/ol061242s
3. Hungerford, N. L.; McLeod, M. D., Steroid metabolite synthesis: the selective manipulation of steroid hydroxyl groups using boronate esters. Access to antigenic C-3 linked steroid conjugates and steroid sulfates. Org. Biomol. Chem. 2006, 4, 3951-3959. DOI: 10.1039/b610499a
4. Louis, I.; Hungerford, N. L.; Humphries, E. J.; McLeod, M. D., Enantioselective total synthesis of (-)-dactylolide. Org. Lett. 2006, 8, 1117-1120. DOI: 10.1021/ol053092b
5. Hungerford, N. L.; Sortais, B.; Smart, C. G.; McKinney, A. R.; Ridley, D. D.; Stenhouse, A. M.; Suann, C. J.; Munn, K. J.; Sillence, M. N.; McLeod, M. D., Analysis of anabolic steroids in the horse: development of a generic ELISA for the screening of 17α-alkyl anabolic steroid metabolites. J. Steroid Biochem. Mol. Biol. 2005, 96, 317-334. DOI: 10.1016/j.jsbmb.2005.03.007

Career Profile:
BSc Hons 1992 (Monash University)
PhD 1997 (University of Cambridge)
Postdoctoral Fellow 1997 (ANU)
Lecturer 1998 (The University of Sydney)
Senior Lecturer 2004 (The University of Sydney)

Areas of interest:
Synthetic Organic and Medicinal Chemistry
Synthesis of Biologically Active Natural Products
Enzyme and Metal Mediated Catalysis

Dr Mal McLeod
Senior Lecturer
Research School of Chemistry
Australian National University
Canberra, ACT 0200
Australia

T: +61 2 6125 3504
F: +61 2 6125 8114
E: m.mcleod at rsc.anu.edu.au