Grant: Collaborative Research and Development Grants

Organic synthesis involves making carbon-based complex molecules from simple ones, just as Lego blocks are*clicked together to form large educational and playful structures. Methods for synthesis have advanced and*multiplied so that today we can make complicated molecules, some of which provide medicines and*agricultural agents for the benefit of humankind. Today, a very active area, especially in industrial laboratories,*is the synthesis of deuterium (D)-containing pharmaceuticals. The replacement of hydrogen (H) of a given drug*with D results in modification/retardation of metabolic fate and alters the therapeutic profile while retaining the*biological potency of the non-D molecules. Thus, the development of D-analogues of currently approved*pharmaceuticals could lead to a positive impact on the safety, efficacy and tolerability of these drugs,*addressing important but unmet medical needs. This proposal aims to address these needs by the synthesis of a*series of D-analogues of currently significant marketed drugs. The proposed research is based on our*considerable experience in the discovery and development of directed ortho metalation (DoM) and related*technologies for the preparation of aromatic and heteroaromatic molecules. These classes of molecules are the*mainstay of pharmaceuticals (80% of modern drugs) and are used by industry (e.g. Monsanto, Pfizer, BMS,*Merck) for the multi-kg synthesis of marketed pharmaceuticals. We also have a strong knowledge base on the*preparation of D-molecules since this is the backbone reaction of our DoM synthetic strategies. Based on this*background and experience, our goals are: a) to incorporate D into commercially available drugs, establishing*synthetic feasibility; b) to develop fundamentally new synthetic steps for introduction of D at early or late*intermediate stages; and c) to develop new routes that truncate known procedures. We anticipate that the*research will provide Sussex Research an advantage over non-Canadian competitors, and thereby will have a*positive impact on the Canadian economy as well as train highly qualified scientists for the Canadian labour*market.