新型细菌拓扑异构酶抑制剂OSUAB-0284的十克规模合成
Decagram-Scale Synthesis of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284.
作者信息
West Jason S, Mann Chelsea A, Mitton-Fry Mark J
机构信息
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
出版信息
Org Process Res Dev. 2025 Mar 26;29(4):1136-1151. doi: 10.1021/acs.oprd.5c00033. eCollection 2025 Apr 18.
Abstract
Medicinal chemistry efforts identified OSUAB-0284 () as a preclinical candidate to treat staphylococcal infections, especially those caused by methicillin-resistant (MRSA). Herein, we describe a fit-for-purpose route that enabled the production of >20 g of API for toxicology studies and further preclinical characterization. Process improvements include a 16-fold increase in yield over the longest sequence, a 21-fold increase in efficiency for the cost-limiting reagent, and reduction of chromatography to one silica plug across an 18-step route.
摘要
药物化学研究确定了OSUAB-0284（）作为治疗葡萄球菌感染的临床前候选药物，尤其是耐甲氧西林（MRSA）引起的感染。在此，我们描述了一种适用的路线，该路线能够生产超过20克的活性药物成分用于毒理学研究和进一步的临床前表征。工艺改进包括在最长的合成序列中收率提高了16倍，成本限制试剂的效率提高了21倍，并且在一条18步的路线中将色谱步骤减少到一个硅胶柱。
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