Grant: Discovery Grants Program - Individual

The central theme of our program involves a combination of chemical and biological methods to maximize efficiency in the manufacturing of important organic compounds. These range from natural products, their medicinally important unnatural derivatives, chiral building blocks and reagents, and chiral polymers. Emphasis is placed on brevity of design and environmentally benign (""green"") execution. These goals are accomplished by multi-generational pursuit of the targets and continuous improvement in synthetic protocols. In addition, and through collaborations with industry, process improvement research is being conducted for compounds of commercial significance, for example, opiate-derived analgesics. During the next funding period, our well-integrated program expands in a number of new directions and is focused on the following areas: (1) Biotransformations of aromatics and provision of chiral building blocks for target-oriented synthesis. (2) Total synthesis of unnatural derivatives of Amaryllidaceae alkaloids with anti-cancer activities. (3) New generation designs for morphine (pain control) and Aspidosperma alkaloids (anti-cancer). (4) Catalytic and enzymatic methods for improved N-demethylation of opiates (pain control). (5) New [5+2] and [5+2+1] annulation protocols. (6) Synthesis of new derivatives of Tamiflu with anti-viral and anti-cancer activities. (7) Design of an enzyme mimic reagent for dihydroxylation of aromatics. Overall, the proposed research addresses focused investigations in asymmetric synthesis driven by the use of biological methods for a greater ""green"" component. The need for more efficient manufacturing processes is essential in order to save diminishing resources and protect the environment. Our research addresses future solutions to manufacturing of important compounds and materials. Highly qualified personnel at undergraduate, graduate, and postdoctoral levels will be trained in biocatalysis, synthesis, catalyst design, and process-development for the Canadian pharmaceutical sector and/or academic appointments. We expect to prepare marketable medicinal agents for commercialization.