Application of new catalytic technologies in the synthesis of substituted piperazines. New approaches for the synthesis of calcium channel blockers for pain treatment.

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Catalytic methods afford energy efficient routes for the synthesis of complex molecules. Recent developments from a pharmaceutical company in Vancouver, British Columbia, Neuromed, have shown that a family of nitrogen containing cyclic compounds, piperazines, can be used for a novel approach toward the treatment of chronic pain. Chronic pain affects the lives of millions of Canadians and costs the country billions in reduced productivity and increased medical costs. Consequently, new orally available treatments that avoid addictive and sedative side-effects that are common with drugs such as Morphine, are highly sought after. This proposal addresses an alternative, catalytic synthetic approach for the rapid and facile synthesis of this class of piperazine products. The catalysts to be employed for this reaction build carbon-nitrogen bonds with no by-products and are a new class of catalysts that take advantage of the low cost and low toxicity of zirconium metal. The proposed synthetic strategy reduces the number of synthetic steps, which in turn reduces waste-streams while accessing a broad range of piperazines which may display desirable biological activity. Neuromed pharmaceuticals will be involved in screening catalytically prepared compounds for favourable activity. Overall, the impact of this new synthetic approach will improve manufacturing efficiency and flexbility to enhance productivity while reducing energy consumption and environmental impacts in the synthesis of this important class of compounds.