{"title":"米尔霉素肟原料药中三个新的异构体杂质的分离鉴定。","authors":"Xiaohan Ren, Jianwei Lu, Yefei Wu, Shaoyong Zhang, Huan Qi, Hui Zhang, Jidong Wang, Linghui Zheng","doi":"10.1038/s41429-024-00791-7","DOIUrl":null,"url":null,"abstract":"In an effort to identification of the unknown impurities in milbemycin oxime (MO) bulk drug, three impurities 1, 2 and 3 were isolated by two-dimensional (2 D) preparation method (Agilent Zorbax-C3 preparative column and Sepax Amethyst C18-H preparative column). Based on the extensive NMR analysis and ESIMS data, the structures of the three impurities were established as 14-desmethyl-14-ethyl-MO A4 (1), 24-desmethyl-24-ethyl-MO A4 (2) and 12-desmethyl-12-ethyl-MO A4 (3), respectively. They are the new isomer impurities of MO D and most likely originate from the oxidation and oximation of natural milbemycin homologs present in the original fermentation broth.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 2","pages":"106-112"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Isolation and identification of three new isomer impurities in milbemycin oxime drug substance\",\"authors\":\"Xiaohan Ren, Jianwei Lu, Yefei Wu, Shaoyong Zhang, Huan Qi, Hui Zhang, Jidong Wang, Linghui Zheng\",\"doi\":\"10.1038/s41429-024-00791-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In an effort to identification of the unknown impurities in milbemycin oxime (MO) bulk drug, three impurities 1, 2 and 3 were isolated by two-dimensional (2 D) preparation method (Agilent Zorbax-C3 preparative column and Sepax Amethyst C18-H preparative column). Based on the extensive NMR analysis and ESIMS data, the structures of the three impurities were established as 14-desmethyl-14-ethyl-MO A4 (1), 24-desmethyl-24-ethyl-MO A4 (2) and 12-desmethyl-12-ethyl-MO A4 (3), respectively. They are the new isomer impurities of MO D and most likely originate from the oxidation and oximation of natural milbemycin homologs present in the original fermentation broth.\",\"PeriodicalId\":54884,\"journal\":{\"name\":\"Journal of Antibiotics\",\"volume\":\"78 2\",\"pages\":\"106-112\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Antibiotics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41429-024-00791-7\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antibiotics","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41429-024-00791-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
为了鉴定米霉素肟原料药中未知杂质,采用二维(2d)制备法(Agilent Zorbax-C3制备柱和Sepax Amethyst C18-H制备柱)分离杂质1、2和3。基于广泛的NMR分析和ESIMS数据,确定了这三种杂质的结构分别为14-去甲基-14-乙基- mo A4(1)、24-去甲基-24-乙基- mo A4(2)和12-去甲基-12-乙基- mo A4(3)。它们是MO D的新异构体杂质,很可能源于原始发酵液中存在的天然milbemycin同源物的氧化和氧化。
Isolation and identification of three new isomer impurities in milbemycin oxime drug substance
In an effort to identification of the unknown impurities in milbemycin oxime (MO) bulk drug, three impurities 1, 2 and 3 were isolated by two-dimensional (2 D) preparation method (Agilent Zorbax-C3 preparative column and Sepax Amethyst C18-H preparative column). Based on the extensive NMR analysis and ESIMS data, the structures of the three impurities were established as 14-desmethyl-14-ethyl-MO A4 (1), 24-desmethyl-24-ethyl-MO A4 (2) and 12-desmethyl-12-ethyl-MO A4 (3), respectively. They are the new isomer impurities of MO D and most likely originate from the oxidation and oximation of natural milbemycin homologs present in the original fermentation broth.
期刊介绍:
The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below:
Discovery of new antibiotics and related types of biologically active substances
Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances
Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances
Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances
Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.