{"title":"以化学和生物化学方法制备千克级对映体纯度的 3,4-二取代四氢呋喃衍生物：KRED 的力量","authors":"Antony Bigot, Alain Rabion, Jean-Bernard Landier, Geoffrey Laronze, Frédéric Petit, Stéphanie Deprets, Jean-Marc Michot, Changxia Yuan, Fenglai Sun, Han Chen, Longlei Hou, Dalin Tang","doi":"10.1021/acs.oprd.4c00388","DOIUrl":null,"url":null,"abstract":"A scalable synthesis of (<i>3S,4S</i>)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3<i>S</i>,4<i>S</i>)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED\",\"authors\":\"Antony Bigot, Alain Rabion, Jean-Bernard Landier, Geoffrey Laronze, Frédéric Petit, Stéphanie Deprets, Jean-Marc Michot, Changxia Yuan, Fenglai Sun, Han Chen, Longlei Hou, Dalin Tang\",\"doi\":\"10.1021/acs.oprd.4c00388\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"A scalable synthesis of (<i>3S,4S</i>)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3<i>S</i>,4<i>S</i>)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.\",\"PeriodicalId\":55,\"journal\":{\"name\":\"Organic Process Research & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-11-14\",\"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.4c00388\",\"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://doi.org/10.1021/acs.oprd.4c00388","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED
A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3S,4S)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
