{"title":"Selective and Scalable O-Alkylation of Serine and Threonine Enabled by Chelation-Controlled Reductive C–N Cleavage of N,O-Acetals","authors":"Keisuke Nogi, Masao Tsukazaki, Hiroshi Iwamura, Kenji Maeda","doi":"10.1021/acs.oprd.4c00543","DOIUrl":null,"url":null,"abstract":"A selective and scalable <i>O</i>-alkylation method has been developed for the synthesis of a series of <i>O</i>-alkyl serine and threonine derivatives as useful unnatural amino acids. The use of Ti(IV) species capable of bis-ligation enables chelation-controlled reductive C–N cleavage of <i>N</i>,<i>O</i>-acetal intermediates to afford the corresponding <i>O</i>-alkylated product. Moreover, <i>N</i>-alkylated byproducts are selectively decomposed under basic conditions and removed by extraction and crystallization, thus eliminating laborious column chromatography processes in scale-up synthesis.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"71 1","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-03-25","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.4c00543","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
A selective and scalable O-alkylation method has been developed for the synthesis of a series of O-alkyl serine and threonine derivatives as useful unnatural amino acids. The use of Ti(IV) species capable of bis-ligation enables chelation-controlled reductive C–N cleavage of N,O-acetal intermediates to afford the corresponding O-alkylated product. Moreover, N-alkylated byproducts are selectively decomposed under basic conditions and removed by extraction and crystallization, thus eliminating laborious column chromatography processes in scale-up synthesis.
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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