Decagram-Scale Synthesis of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-03-26 DOI:10.1021/acs.oprd.5c00033

Jason S. West, Chelsea A. Mann, Mark J. Mitton-Fry

引用次数: 0

Abstract

Medicinal chemistry efforts identified OSUAB-0284 (2) as a preclinical candidate to treat staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (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.

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新型细菌拓扑异构酶抑制剂OSUAB-0284的十克级合成

药物化学方面的努力确定OSUAB-0284(2)是治疗葡萄球菌感染的临床前候选药物，特别是耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染。在这里，我们描述了一种适合目的的路线，使生产20克原料药用于毒理学研究和进一步的临床前表征。工艺改进包括最长序列的产量提高16倍，成本限制试剂的效率提高21倍，并且在18步路线中减少了一个硅胶塞的色谱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.