{"title":"酮还原酶介导的 1,1-二取代环丁烷-3-醇立体异构合成","authors":"Hardwin O’Dowd*, and , Olivia M. Morales, ","doi":"10.1021/acs.oprd.4c00126","DOIUrl":null,"url":null,"abstract":"<p >Selective access to both <i>cis</i>- and <i>trans</i>-isomers of α-substituted 3-hydroxycyclobutane-1-carboxylic esters has been demonstrated using ketoreductase (KRED) enzymes. Two stereocomplementary KREDs were identified from a commercial panel that are highly selective for small α-substituents when the ester group was <i>para</i>-methoxybenzyl. Probing the substrate scope of these two enzymes revealed that the selectivity declined rapidly with both when increasing the steric bulk of the α-substituent. For methyl ester substrates with larger α-substituents, a different pair of KREDs was identified with excellent selectivity for both the <i>cis-</i> and <i>trans</i>-isomers for a small range of substrates. The cyclobutanol products serve as precursors to other synthetically useful building blocks such as amino acids.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ketoreductase-Mediated Stereodivergent Synthesis of 1,1-Disubstituted Cyclobutan-3-ols\",\"authors\":\"Hardwin O’Dowd*, and , Olivia M. Morales, \",\"doi\":\"10.1021/acs.oprd.4c00126\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Selective access to both <i>cis</i>- and <i>trans</i>-isomers of α-substituted 3-hydroxycyclobutane-1-carboxylic esters has been demonstrated using ketoreductase (KRED) enzymes. Two stereocomplementary KREDs were identified from a commercial panel that are highly selective for small α-substituents when the ester group was <i>para</i>-methoxybenzyl. Probing the substrate scope of these two enzymes revealed that the selectivity declined rapidly with both when increasing the steric bulk of the α-substituent. For methyl ester substrates with larger α-substituents, a different pair of KREDs was identified with excellent selectivity for both the <i>cis-</i> and <i>trans</i>-isomers for a small range of substrates. The cyclobutanol products serve as precursors to other synthetically useful building blocks such as amino acids.</p>\",\"PeriodicalId\":55,\"journal\":{\"name\":\"Organic Process Research & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-05-21\",\"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.4c00126\",\"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.4c00126","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Ketoreductase-Mediated Stereodivergent Synthesis of 1,1-Disubstituted Cyclobutan-3-ols
Selective access to both cis- and trans-isomers of α-substituted 3-hydroxycyclobutane-1-carboxylic esters has been demonstrated using ketoreductase (KRED) enzymes. Two stereocomplementary KREDs were identified from a commercial panel that are highly selective for small α-substituents when the ester group was para-methoxybenzyl. Probing the substrate scope of these two enzymes revealed that the selectivity declined rapidly with both when increasing the steric bulk of the α-substituent. For methyl ester substrates with larger α-substituents, a different pair of KREDs was identified with excellent selectivity for both the cis- and trans-isomers for a small range of substrates. The cyclobutanol products serve as precursors to other synthetically useful building blocks such as amino acids.
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.