Development of a Scalable Anodic Oxidation Process for (R)-Troloxamide Quinone (EPI-589) Using a Continuous Flow Approach

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-03-28 DOI:10.1021/acs.oprd.5c00016

Hirotsugu Usutani, Jun Hirabayashi, Kenji Yamamoto, Xinlong Gao, Jianghong Chen, Jianye Jiao, Hsiao Yi, Pan Wang, Kazuki Hashimoto

{"title":"Development of a Scalable Anodic Oxidation Process for (R)-Troloxamide Quinone (EPI-589) Using a Continuous Flow Approach","authors":"Hirotsugu Usutani, Jun Hirabayashi, Kenji Yamamoto, Xinlong Gao, Jianghong Chen, Jianye Jiao, Hsiao Yi, Pan Wang, Kazuki Hashimoto","doi":"10.1021/acs.oprd.5c00016","DOIUrl":null,"url":null,"abstract":"Electrochemical methods in organic synthesis hold significant potential for next-generation chemical processes and are gaining attention not only in the pharmaceutical sector but also across the broader chemical industry. From an electrochemical perspective, electrons can be regarded as a reagent, which can be utilized in various oxidation and reduction reactions. Anodic oxidation is one example, by which it is possible to oxidatively cleave troloxamide to form troloxamide quinone. Thus, an electrochemical process can contribute to the synthesis of the active pharmaceutical ingredient (API) EPI-589, a drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). Process development using electrochemical methods is often regarded as challenging for scale-up and manufacturing, but here we describe the establishment of a manufacturing method by combining the concepts of anodic oxidation (electroorganic chemistry) and continuous processing are described. The results of a scale-up proof-of-concept experiment are shown, in which the API was obtained with excellent quality on a kilogram scale.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"19 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.oprd.5c00016","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}

引用次数: 0

Abstract

Electrochemical methods in organic synthesis hold significant potential for next-generation chemical processes and are gaining attention not only in the pharmaceutical sector but also across the broader chemical industry. From an electrochemical perspective, electrons can be regarded as a reagent, which can be utilized in various oxidation and reduction reactions. Anodic oxidation is one example, by which it is possible to oxidatively cleave troloxamide to form troloxamide quinone. Thus, an electrochemical process can contribute to the synthesis of the active pharmaceutical ingredient (API) EPI-589, a drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). Process development using electrochemical methods is often regarded as challenging for scale-up and manufacturing, but here we describe the establishment of a manufacturing method by combining the concepts of anodic oxidation (electroorganic chemistry) and continuous processing are described. The results of a scale-up proof-of-concept experiment are shown, in which the API was obtained with excellent quality on a kilogram scale.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.