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

催化方法为复杂分子的合成提供了高效节能的途径。来自不列颠哥伦比亚省温哥华一家制药公司Neuromed的最新进展表明，一种含氮环状化合物哌嗪家族可用于治疗慢性疼痛的新方法。慢性疼痛影响了数百万加拿大人的生活，并使该国在生产力下降和医疗费用增加方面损失了数十亿美元。因此，新的口服治疗方法受到高度追捧，这些方法避免了吗啡等药物常见的成瘾性和镇静副作用。本提案提出了一种替代的催化合成方法，用于快速简便地合成这类哌嗪产品。用于该反应的催化剂是一种新型催化剂，它利用了金属锆的低成本和低毒的优点，建立了无副产物的碳-氮键。所提出的合成策略减少了合成步骤的数量，从而减少了废物流，同时获得了广泛的哌嗪，这些哌嗪可能显示出理想的生物活性。神经医学药物将参与筛选催化制备的具有有利活性的化合物。总的来说，这种新的合成方法的影响将提高制造效率和灵活性，以提高生产率，同时减少这类重要化合物合成的能源消耗和环境影响。

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.