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

催化方法为合成复杂分子提供了能源高效的途径。不列颠哥伦比亚省温哥华的一家制药公司Neuromed最近的研究表明，一种含有氮环化合物的家族--哌嗪--可以用于治疗慢性疼痛的新方法。慢性疼痛影响着数百万加拿大人的生活，并使该国因生产力下降和医疗费用增加而损失数十亿美元。因此，避免吗啡等药物常见的成瘾和镇静副作用的新口服治疗方法备受追捧。这项建议介绍了一种替代的催化合成方法，用于快速和简便地合成这类哌嗪产品。用于该反应的催化剂建立了碳-氮键，没有副产物，是一种新型的催化剂，利用了金属锆的低成本和低毒性。拟议的合成策略减少了合成步骤的数量，这反过来又减少了废物流，同时获得了可能显示出理想生物活性的广泛的哌嗪。Neuromed制药公司将参与筛选具有良好活性的催化制备的化合物。总体而言，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，同时减少这一重要类别化合物的合成过程中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.