{"title":"多耐药性药物氯法齐明的连续流合成","authors":"Rajat Pandey, Faith Akwi and Paul Watts*, ","doi":"10.1021/acs.oprd.4c0042010.1021/acs.oprd.4c00420","DOIUrl":null,"url":null,"abstract":"<p >Drug resistance to tuberculosis is still one of the major challenges worldwide. Clofazimine, which belongs to the riminophenazine (antibiotic) class, is still one of the active drugs that are efficient against drug-resistant <i>Mycobacterium tuberculosis</i>. Apart from this, it is also a WHO-approved drug for the treatment of leprosy and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a semicontinuous flow-mediated synthesis of Clofazimine using readily available <i>p</i>-chloroaniline and 1-fluoro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal residence time, improved purity, and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under the optimized reaction conditions.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"28 11","pages":"4163–4172 4163–4172"},"PeriodicalIF":3.1000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.oprd.4c00420","citationCount":"0","resultStr":"{\"title\":\"Continuous Flow Enabled Synthesis of Multiresistant Drug Clofazimine\",\"authors\":\"Rajat Pandey, Faith Akwi and Paul Watts*, \",\"doi\":\"10.1021/acs.oprd.4c0042010.1021/acs.oprd.4c00420\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Drug resistance to tuberculosis is still one of the major challenges worldwide. Clofazimine, which belongs to the riminophenazine (antibiotic) class, is still one of the active drugs that are efficient against drug-resistant <i>Mycobacterium tuberculosis</i>. Apart from this, it is also a WHO-approved drug for the treatment of leprosy and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a semicontinuous flow-mediated synthesis of Clofazimine using readily available <i>p</i>-chloroaniline and 1-fluoro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal residence time, improved purity, and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under the optimized reaction conditions.</p>\",\"PeriodicalId\":55,\"journal\":{\"name\":\"Organic Process Research & Development\",\"volume\":\"28 11\",\"pages\":\"4163–4172 4163–4172\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acs.oprd.4c00420\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Process Research & Development\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00420\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00420","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Continuous Flow Enabled Synthesis of Multiresistant Drug Clofazimine
Drug resistance to tuberculosis is still one of the major challenges worldwide. Clofazimine, which belongs to the riminophenazine (antibiotic) class, is still one of the active drugs that are efficient against drug-resistant Mycobacterium tuberculosis. Apart from this, it is also a WHO-approved drug for the treatment of leprosy and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a semicontinuous flow-mediated synthesis of Clofazimine using readily available p-chloroaniline and 1-fluoro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal residence time, improved purity, and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under the optimized reaction conditions.
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.
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