{"title":"不含 TosMIC 的高胆固醇血症药物鱼藤酸的合成","authors":"B.V. Subba reddy, Rachel Gundamalla, Rajashaker Bantu","doi":"10.24820/ark.5550190.p012.204","DOIUrl":null,"url":null,"abstract":"A novel concise and convergent approach for the preparation of bempedoic acid, a new group of non-statin LDL-lowering drug has been developed starting from pentane-1,5-diol in 8 steps with an overall yield of 20%. Result: The synthesis of a key precursor i.e. 1,11-dihydroxyundecan-6-one, has been accomplished through the ring opening of - caprolactone with alkyl Grignard reagent. This method doesn’t require the use of p - toluenesulfonylmethylisocyanaide (TosMIC) for the construction of dihyroxyketone, a key intermediate of bempedoic acid. The key steps involved in this approach are the bromination of dihydroxyketone and base-catalyzed alkylation of methyl isobutyrate with 1,11-dibromoundecan-6-ol followed by the hydrolysis of dimethyl ester into bempedoic acid.","PeriodicalId":8432,"journal":{"name":"Arkivoc","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TosMIC-free synthesis of bempedoic acid, a hypercholesterolemia drug\",\"authors\":\"B.V. Subba reddy, Rachel Gundamalla, Rajashaker Bantu\",\"doi\":\"10.24820/ark.5550190.p012.204\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"A novel concise and convergent approach for the preparation of bempedoic acid, a new group of non-statin LDL-lowering drug has been developed starting from pentane-1,5-diol in 8 steps with an overall yield of 20%. Result: The synthesis of a key precursor i.e. 1,11-dihydroxyundecan-6-one, has been accomplished through the ring opening of - caprolactone with alkyl Grignard reagent. This method doesn’t require the use of p - toluenesulfonylmethylisocyanaide (TosMIC) for the construction of dihyroxyketone, a key intermediate of bempedoic acid. The key steps involved in this approach are the bromination of dihydroxyketone and base-catalyzed alkylation of methyl isobutyrate with 1,11-dibromoundecan-6-ol followed by the hydrolysis of dimethyl ester into bempedoic acid.\",\"PeriodicalId\":8432,\"journal\":{\"name\":\"Arkivoc\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2024-07-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arkivoc\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.24820/ark.5550190.p012.204\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arkivoc","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.24820/ark.5550190.p012.204","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
TosMIC-free synthesis of bempedoic acid, a hypercholesterolemia drug
A novel concise and convergent approach for the preparation of bempedoic acid, a new group of non-statin LDL-lowering drug has been developed starting from pentane-1,5-diol in 8 steps with an overall yield of 20%. Result: The synthesis of a key precursor i.e. 1,11-dihydroxyundecan-6-one, has been accomplished through the ring opening of - caprolactone with alkyl Grignard reagent. This method doesn’t require the use of p - toluenesulfonylmethylisocyanaide (TosMIC) for the construction of dihyroxyketone, a key intermediate of bempedoic acid. The key steps involved in this approach are the bromination of dihydroxyketone and base-catalyzed alkylation of methyl isobutyrate with 1,11-dibromoundecan-6-ol followed by the hydrolysis of dimethyl ester into bempedoic acid.
期刊介绍:
Arkivoc publishes full papers (not accounts) describing sound original work that is of interest to organic chemists (in areas of synthetic organic chemistry, bio-organic, organometallic, theoretical, and physical organic chemistry:
General Papers describing sound original work
Reviews and Accounts of selected topics
Honorary Issues - Pay tribute to distinguished organic chemists (invited contributions)
Thematic Issues - Cover important current topics in organic chemistry
Regional Issues - Recognize organic chemistry in various countries.