Caroline A. Blakemore*, John M. Humphrey, Eddie Yang, Jeffrey T. Kohrt, Peter Daniel Morse, Roger M. Howard, Hatice G. Yayla, Thomas Knauber, Longfei Xie, Teresa Makowski, Jeffrey W. Raggon, Rebecca B. Watson, Christopher W. am Ende, Tim Ryder, Ormacinda White, Martin R. M. Koos, Rajesh Kumar, Feng Shi, Jie Li, Huan Wang, Like Chen and Julai Wang,
{"title":"Synthesis of Enantiopure Fluoropiperidines via Biocatalytic Desymmetrization and Flow Photochemical Decarboxylative Fluorination","authors":"Caroline A. Blakemore*, John M. Humphrey, Eddie Yang, Jeffrey T. Kohrt, Peter Daniel Morse, Roger M. Howard, Hatice G. Yayla, Thomas Knauber, Longfei Xie, Teresa Makowski, Jeffrey W. Raggon, Rebecca B. Watson, Christopher W. am Ende, Tim Ryder, Ormacinda White, Martin R. M. Koos, Rajesh Kumar, Feng Shi, Jie Li, Huan Wang, Like Chen and Julai Wang, ","doi":"10.1021/acs.oprd.4c0013910.1021/acs.oprd.4c00139","DOIUrl":null,"url":null,"abstract":"<p >Low-molecular weight chiral amines are valuable components in medicinal chemistry as they serve as core templates, linking units, and substituent appendages. The piperidine scaffold is particularly useful among privileged small amines, with substituted variants having a great number of potential regio- and diastereoisomers, which allow for high stereochemical definition to enable a variety of productive protein interactions. Herein, we describe the successful enablement, scale-up, and delivery of >400 g of a single isomer, (3<i>S</i>,5<i>S</i>)-1-((benzyloxy)carbonyl)-5-fluoropiperidine-3-carboxylic acid (>98% de and >96% ee), via 450 g-scale biocatalytic desymmetrization and 335 g-scale flow photochemical decarboxylative fluorination.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-09-30","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://pubs.acs.org/doi/10.1021/acs.oprd.4c00139","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
Low-molecular weight chiral amines are valuable components in medicinal chemistry as they serve as core templates, linking units, and substituent appendages. The piperidine scaffold is particularly useful among privileged small amines, with substituted variants having a great number of potential regio- and diastereoisomers, which allow for high stereochemical definition to enable a variety of productive protein interactions. Herein, we describe the successful enablement, scale-up, and delivery of >400 g of a single isomer, (3S,5S)-1-((benzyloxy)carbonyl)-5-fluoropiperidine-3-carboxylic acid (>98% de and >96% ee), via 450 g-scale biocatalytic desymmetrization and 335 g-scale flow photochemical decarboxylative fluorination.
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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