Professor Stephen Pyne School of Chemistry, University of Wollongong, New South Wales 2522, Australia  Research within the Pyne group is concerned with a number of projects that involve the organic chemical synthesis of bioactive molecules. This includes:  The total synthesis of bioactive azasugar alkaloids with potential applications as anti-diabetic drugs.  The total synthesis of bioactive Stemona alkaloids with potential applications as acetylcholinesterase inhibitors (useful in Alzheimer's disease).  The discovery of new chemical reactions to prepare novel drug-like scaffolds for new drug discovery (with Eli Lilly)  The development of organoboron reagents in conjunction with metal-catalysed reactions to prepare bioactive heterocycles.  The development of new antibacterials active against pathogenic bacteria and Clostridium difficile infections.  Other projects include natural products chemistry in collaboration with scientists in Thailand and Nigeria. The total synthesis of bioactive azasugar alkaloids with potential applications as anti-diabetic drugs We have and are currently developing novel concise chemical synthesis methods for preparing a number of bioactive azasugar alkaloids that have glycosidase inhibitory activities and thus have potential to be developed as anti-diabetic drugs. We have employed the borono-Mannich reaction to prepare many of these alkaloids as shown below in the Scheme. Organic Chemical Synthesis Projects Acknowledgements This research is supported by the Australian Research Council, the NHMRC and the University of Wollongong. Previous work: correction of the structure of the anti-diabetic alkaloid Uniflorine A Uniflorine A was isolated in 2000 from the leaves of the tree Eugenia uniflora L. The water-soluble extract of these leaves has been used as an antidiabetic agent in Paraguayan traditional medicine. Our synthetic studies resulted in us correcting the structure of uniflorine A from a suggested indolizidine to a pyrrolizidine. Eugenia uniflora L. (Surinam cherry) Ritthiwigrom, Pyne, Org. Lett. 2008, 10, ; J. Org. Chem. 2010, 75, Previous work: the successful synthesis of other alkaloids for structure confirmation and biological testing as glycosidase inhibitors Current work: the synthesis, structure confirmation and glycosidase activity of the hyacinthacine C alkaloids isolated from Other bioactive alkaloid targets for synthesis: Biological Screening Assays (Eli Lilly Open Drug Discovery Program) Synthesis of natural product like scaffolds for new drug discovery Drugs to treat drug resistant bacterial and Clostridium difficile Infections (with Paul Keller) Earlier we discovered a novel series of active binaphthyl, dicationic peptide-based compounds which show antibacterial activity that is generally close to, or better than, that of vancomycin against Staphylococcus aureus and S. epidermidis and superior against vancomycin resistant Enterococcus faecium (VRE). From our large collection of >200 compounds, two of our peptides showed in vitro antibacterial potency against a range of Gram-positive pathogens including strains of S. aureus resistant to vancomycin, methicillin, and linezolid. Examples from our peptide class of antibiotics. These studies gave rise to the commercial development of two examples by Valevia for antimicrobial applications, which make this class of compounds an exciting prospect for further antibacterial drug discovery. We are now aiming to further advance our peptide antibiotics into efficacious therapeutics to treat C. difficile infection.