{"title":"Synthesis, Characterization, and Control Strategies for Cabazitaxel-Related Substances at Scale","authors":"Amarendhar Manda, Shravan Kumar Komati, Debjit Basu, Gopal Chandru Senadi, Arthanareeswari Maruthapillai, Rakeshwar Bandichhor","doi":"10.1021/acs.oprd.4c00414","DOIUrl":null,"url":null,"abstract":"Cabazitaxel <b>1</b> is an antineoplastic agent belonging to the taxane class and approved for the treatment of hormone-refractory prostate cancer. During the optimization process of cabazitaxel, six related substances were detected using the gradient high-performance liquid chromatography technique. A thorough study was undertaken to identify, prepare, and control these six related substances. The molecular weights were determined by liquid chromatography–mass spectrometry analysis. Using spectroscopic analysis (high-resolution mass spectrometry (HRMS), infrared (IR), and NMR), the structures were determined as an amino alcohol derivative (CRS-1), 7,10-dimethoxy-10-deacetylbaccatin III (CRS-2), an <i>N</i>-formyl-related substance (CRS-3), 7,10,13-trimethoxy-10-deacetylbaccatin III (CRS-4), a DiBOC-related substance (CRS-5), and a process-related intermediate (CRS-6). The mechanistic aspects of the formation, synthesis, and control strategy of the associated substances were examined in detail.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"1 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2024-12-16","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.4c00414","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
Cabazitaxel 1 is an antineoplastic agent belonging to the taxane class and approved for the treatment of hormone-refractory prostate cancer. During the optimization process of cabazitaxel, six related substances were detected using the gradient high-performance liquid chromatography technique. A thorough study was undertaken to identify, prepare, and control these six related substances. The molecular weights were determined by liquid chromatography–mass spectrometry analysis. Using spectroscopic analysis (high-resolution mass spectrometry (HRMS), infrared (IR), and NMR), the structures were determined as an amino alcohol derivative (CRS-1), 7,10-dimethoxy-10-deacetylbaccatin III (CRS-2), an N-formyl-related substance (CRS-3), 7,10,13-trimethoxy-10-deacetylbaccatin III (CRS-4), a DiBOC-related substance (CRS-5), and a process-related intermediate (CRS-6). The mechanistic aspects of the formation, synthesis, and control strategy of the associated substances were examined in detail.
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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