Bohdan Moroz , Kostiantyn P. Melnykov , Serhii Holovach , Andrey A. Filatov , Oleksii Raievskyi , Maksym Platonov , Oleksandr Liashuk , Dmytro M. Volochnyuk , Oleksandr O. Grygorenko
{"title":"6,6-二氟双环[3.1.0]己烷作为刚性4,4-二氟环己烷的模拟物:多重图合成、物理化学表征和纳入马拉维洛克类似物","authors":"Bohdan Moroz , Kostiantyn P. Melnykov , Serhii Holovach , Andrey A. Filatov , Oleksii Raievskyi , Maksym Platonov , Oleksandr Liashuk , Dmytro M. Volochnyuk , Oleksandr O. Grygorenko","doi":"10.1016/j.jfluchem.2023.110215","DOIUrl":null,"url":null,"abstract":"<div><p>Multigram synthesis of diastereomerically pure <em>cis</em>- and <em>trans</em>-6,6-difluorobicyclo[3.1.0]hexane building blocks starting from commercially available compounds is described. The diastereomeric mixture obtained by reaction of TMSCF<sub>3</sub> – NaI system with non-activated cyclopentene fragment using the slow addition protocol was effectively separated by flash column chromatography. Further simple chemical transformations produced diastereopure amines and carboxylic acids – promising building blocks for drug discovery. Physicochemical properties (i.e., p<em>K</em><sub>a</sub> and Log<em>P</em>) were measured for the title scaffold derivatives and compared with those with monocyclic and non-fluorinated counterparts. Two rigidified analogues of marketed anti-HIV drug Maraviroc were synthesized and evaluated by docking and molecular dynamics studies.</p></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"272 ","pages":"Article 110215"},"PeriodicalIF":1.7000,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022113923001306/pdfft?md5=6b209a7e966e9b87dc7824b606cbc60e&pid=1-s2.0-S0022113923001306-main.pdf","citationCount":"0","resultStr":"{\"title\":\"6,6-Difluorobicyclo[3.1.0]hexane as a Rigidified 4,4-Difluorocyclohexane Mimetic: Multigram Synthesis, Physicochemical Characterization, and Incorporation into Maraviroc Analogs\",\"authors\":\"Bohdan Moroz , Kostiantyn P. Melnykov , Serhii Holovach , Andrey A. Filatov , Oleksii Raievskyi , Maksym Platonov , Oleksandr Liashuk , Dmytro M. Volochnyuk , Oleksandr O. Grygorenko\",\"doi\":\"10.1016/j.jfluchem.2023.110215\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Multigram synthesis of diastereomerically pure <em>cis</em>- and <em>trans</em>-6,6-difluorobicyclo[3.1.0]hexane building blocks starting from commercially available compounds is described. The diastereomeric mixture obtained by reaction of TMSCF<sub>3</sub> – NaI system with non-activated cyclopentene fragment using the slow addition protocol was effectively separated by flash column chromatography. Further simple chemical transformations produced diastereopure amines and carboxylic acids – promising building blocks for drug discovery. Physicochemical properties (i.e., p<em>K</em><sub>a</sub> and Log<em>P</em>) were measured for the title scaffold derivatives and compared with those with monocyclic and non-fluorinated counterparts. Two rigidified analogues of marketed anti-HIV drug Maraviroc were synthesized and evaluated by docking and molecular dynamics studies.</p></div>\",\"PeriodicalId\":357,\"journal\":{\"name\":\"Journal of Fluorine Chemistry\",\"volume\":\"272 \",\"pages\":\"Article 110215\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2023-11-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0022113923001306/pdfft?md5=6b209a7e966e9b87dc7824b606cbc60e&pid=1-s2.0-S0022113923001306-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Fluorine Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022113923001306\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Fluorine Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022113923001306","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
6,6-Difluorobicyclo[3.1.0]hexane as a Rigidified 4,4-Difluorocyclohexane Mimetic: Multigram Synthesis, Physicochemical Characterization, and Incorporation into Maraviroc Analogs
Multigram synthesis of diastereomerically pure cis- and trans-6,6-difluorobicyclo[3.1.0]hexane building blocks starting from commercially available compounds is described. The diastereomeric mixture obtained by reaction of TMSCF3 – NaI system with non-activated cyclopentene fragment using the slow addition protocol was effectively separated by flash column chromatography. Further simple chemical transformations produced diastereopure amines and carboxylic acids – promising building blocks for drug discovery. Physicochemical properties (i.e., pKa and LogP) were measured for the title scaffold derivatives and compared with those with monocyclic and non-fluorinated counterparts. Two rigidified analogues of marketed anti-HIV drug Maraviroc were synthesized and evaluated by docking and molecular dynamics studies.
期刊介绍：
The Journal of Fluorine Chemistry contains reviews, original papers and short communications. The journal covers all aspects of pure and applied research on the chemistry as well as on the applications of fluorine, and of compounds or materials where fluorine exercises significant effects. This can include all chemistry research areas (inorganic, organic, organometallic, macromolecular and physical chemistry) but also includes papers on biological/biochemical related aspects of Fluorine chemistry as well as medicinal, agrochemical and pharmacological research. The Journal of Fluorine Chemistry also publishes environmental and industrial papers dealing with aspects of Fluorine chemistry on energy and material sciences. Preparative and physico-chemical investigations as well as theoretical, structural and mechanistic aspects are covered. The Journal, however, does not accept work of purely routine nature.
For reviews and special issues on particular topics of fluorine chemistry or from selected symposia, please contact the Regional Editors for further details.
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