宾夕法尼亚州立大学光化学新法把磺酰胺转为苯胺：无需另加催化剂，葛兰素史克测算逾 90% 市售磺酰胺可用此法改造
宾夕法尼亚州立大学 11 月 11 日报道，该校化学家带领的团队发现一种简单的光化学技术，可把一类难以改造的化合物磺酰胺，转化为另一类有用的化合物苯胺，为失败候选药物的回收再利用开出新路径。论文发表于 Journal of the American Chemical Society 期刊。
报道称，制药公司保有庞大的化合物库供新药筛选，磺酰胺用于抗生素以及治疗 2 型糖尿病、高血压与炎症的药物，这类化合物在库中数以千计，但因难以化学改造，用途被限制在最初目的之内。苯胺则用于包括数种抗癌药在内的其他药物。
团队负责人、宾夕法尼亚州立大学 Eberly 理学院化学助理教授 Eric Nacsa 说，每种上市药物通常都需要制备并评估成千上万个分子，团队希望设计能把已有简单分子以更少步骤快速转化为目标分子的合成方法，缩短找到理想药物结构的时间。
新方法把磺酰胺转为苯胺只需一步操作，包含两个环节：先用磷酸钾去除磺酰胺分子的一个质子，再让其接受可见光照射，引发反应去除分子另一部分，完成转化。
Nacsa 说，无需另加任何化学催化剂就能完成这一转化完全出乎意料，所用的单项过程都是标准化学，难点在于弄清其作用细节。
团队与葛兰素史克及佛罗里达州立大学的合作者在研究中显示，去质子后，光促使氮原子与磺酰胺中的碳原子成键，并把二氧化硫从分子中切除。Nacsa 说，去除硫原子会显著改变化合物的生物学性质，葛兰素史克的计算研究显示，逾 90% 的市售磺酰胺可用这一技术改造。
Penn State Photochemical Method Converts Sulfonamides to Anilines Without Added Catalysts: GSK Calculations Suggest More Than 90 Percent of Commercial Sulfonamides Could Be Modified
New research led by Penn State chemists has uncovered a simple photochemical technique that converts sulfonamides into anilines, the university reported on November 11. The paper describing the research appeared in the Journal of the American Chemical Society.
Drug companies maintain large libraries of chemical compounds that can be screened for new pharmaceuticals. Sulfonamides are used in antibiotics and in drugs to treat type 2 diabetes, hypertension and inflammation. Thousands of these sulfonamides exist in these libraries, but their use beyond their initial purpose is limited because they are difficult to chemically modify. Anilines are used in other pharmaceuticals, including several cancer drugs.
Eric Nacsa, assistant professor of chemistry in the Penn State Eberly College of Science and leader of the research team, said every drug brought to market usually requires a discovery campaign involving the preparation and biological evaluation of thousands of individual molecules, and that the goal is to convert simpler existing molecules into what is wanted in fewer operations and less time.
The new method converts sulfonamides to anilines in a simple operation involving two underlying events, Nacsa explained. First, potassium phosphate removes a proton from the sulfonamide molecule. The sulfonamide is then exposed to visible light, which initiates a chemical reaction to remove another part of the molecule, completing the conversion.
Nacsa said the ability to perform this transformation without adding any further chemical catalysts was a total surprise, adding that the individual processes used are all standard chemistry, while figuring out why it works was a challenge.
Working with collaborators at Penn State, GlaxoSmithKline and Florida State University, the team showed how, after the proton is removed, light causes a nitrogen atom to bond to a carbon atom in the sulfonamide, clipping out sulfur dioxide from the molecule. Nacsa said removing the sulfur atom dramatically changes the biological properties of the compound, and that GSK computational studies suggested more than 90 percent of commercially available sulfonamides could be modified using this technique.
发布：GSM·美国（发布链接）
图片来源：图：苯胺的化学结构式图，苯环连着一个氨基。Emeldir (talk) 供图，公共领域，经 Wikimedia Commons / Photo: Aniline 200. By Emeldir (talk), public domain, via Wikimedia Commons
GSM Global · 本篇英文版 English edition of this story
