Total Synthesis, Structure Reassignment, and Biological Evaluation of the Anti-Inflammatory Macrolactone 13-Hydroxy-14-deoxyoxacyclododecindione
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Kevin Seipp
- Claudia Kammler
- Nils Ole Rossdam
- Paul Eckhardt
- Anna Maria Kiefer
- Gerhard Erkel
- Till Opatz
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001195065900001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1021/acs.jnatprod.4c00082
- eISSN
- 1520-6025
- Externe Identifier
- Clarivate Analytics Document Solution ID: MQ3X5
- PubMed Identifier: 38555526
- ISSN
- 0163-3864
- Zeitschrift
- JOURNAL OF NATURAL PRODUCTS
- Datum der Veröffentlichung
- 2024
- Status
- Published
- Titel
- Total Synthesis, Structure Reassignment, and Biological Evaluation of the Anti-Inflammatory Macrolactone 13-Hydroxy-14-deoxyoxacyclododecindione
- Sub types
- Article
- Early Access
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Kevin Seipp
- Claudia Kammler
- Nils Ole Rossdam
- Paul Eckhardt
- Anna Maria Kiefer
- Gerhard Erkel
- Till Opatz
- DOI
- 10.1021/acs.jnatprod.4c00082
- eISSN
- 1520-6025
- ISSN
- 0163-3864
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Journal of Natural Products
- Sprache
- en
- Online publication date
- 2024
- Paginierung
- 1131 - 1149
- Datum der Veröffentlichung
- 2024
- Status
- Published
- Herausgeber
- American Chemical Society (ACS)
- Herausgeber URL
- http://dx.doi.org/10.1021/acs.jnatprod.4c00082
- Datum der Datenerfassung
- 2024
- Titel
- Total Synthesis, Structure Reassignment, and Biological Evaluation of the Anti-Inflammatory Macrolactone 13-Hydroxy-14-deoxyoxacyclododecindione
- Ausgabe der Zeitschrift
- 87
Datenquelle: Crossref
- Abstract
- Herein, the first total synthesis of natural 13-hydroxy-14-deoxyoxacyclododecindione along with the revision of the proposed configuration is reported. This natural product, initially discovered in 2018, belongs to the oxacyclododecindione family, renowned for their remarkable anti-inflammatory and antifibrotic activities. The synthetic route involves an esterification/Friedel-Crafts-acylation approach and uses various triol fragments. It allows the preparation of different stereoisomers, including the (revised) natural product, two <i>threo</i>-derivatives, and two <i>Z</i>-isomers of the endocyclic C═C double bond. Furthermore, a late-stage inversion of the C-13 stereocenter could transform the originally proposed structure into the revised natural product. With this comprehensive set of compounds and the previously prepared (13<i>R</i>,14<i>S</i>,15<i>R</i>)-isomer, deeper insights into their structural properties and biological activities were obtained. A detailed analysis of the final macrolactones using spectroscopy (NMR, IR, UV-vis) and X-ray crystallography gave new insights such as the significance of the optical rotation for the elucidation of their configuration and the light-induced <i>E</i>/<i>Z</i> double-bond photoisomerization. The pharmacological potential of the compounds was underlined by remarkably low IC<sub>50</sub> values in biological assays addressing the inhibition of cellular inflammatory responses.
- Addresses
- Department of Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
- Autoren
- Kevin Seipp
- Claudia Kammler
- Nils Ole Rossdam
- Paul Eckhardt
- Anna Maria Kiefer
- Gerhard Erkel
- Till Opatz
- DOI
- 10.1021/acs.jnatprod.4c00082
- eISSN
- 1520-6025
- Externe Identifier
- PubMed Identifier: 38555526
- Funding acknowledgements
- Johannes Gutenberg-Universit?t Mainz:
- Rhineland-Palatinate Ministry of Science and Health:
- Open access
- false
- ISSN
- 0163-3864
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Journal of natural products
- Schlüsselwörter
- Humans
- Lactones
- Macrolides
- Anti-Inflammatory Agents
- Biological Products
- Molecular Structure
- Stereoisomerism
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2024
- Paginierung
- 1131 - 1149
- Datum der Veröffentlichung
- 2024
- Status
- Published
- Datum der Datenerfassung
- 2024
- Titel
- Total Synthesis, Structure Reassignment, and Biological Evaluation of the Anti-Inflammatory Macrolactone 13-Hydroxy-14-deoxyoxacyclododecindione.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 87
Datenquelle: Europe PubMed Central
- Abstract
- Herein, the first total synthesis of natural 13-hydroxy-14-deoxyoxacyclododecindione along with the revision of the proposed configuration is reported. This natural product, initially discovered in 2018, belongs to the oxacyclododecindione family, renowned for their remarkable anti-inflammatory and antifibrotic activities. The synthetic route involves an esterification/Friedel-Crafts-acylation approach and uses various triol fragments. It allows the preparation of different stereoisomers, including the (revised) natural product, two threo-derivatives, and two Z-isomers of the endocyclic C═C double bond. Furthermore, a late-stage inversion of the C-13 stereocenter could transform the originally proposed structure into the revised natural product. With this comprehensive set of compounds and the previously prepared (13R,14S,15R)-isomer, deeper insights into their structural properties and biological activities were obtained. A detailed analysis of the final macrolactones using spectroscopy (NMR, IR, UV-vis) and X-ray crystallography gave new insights such as the significance of the optical rotation for the elucidation of their configuration and the light-induced E/Z double-bond photoisomerization. The pharmacological potential of the compounds was underlined by remarkably low IC50 values in biological assays addressing the inhibition of cellular inflammatory responses.
- Autoren
- Kevin Seipp
- Claudia Kammler
- Nils Ole Rossdam
- Paul Eckhardt
- Anna Maria Kiefer
- Gerhard Erkel
- Till Opatz
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/38555526
- DOI
- 10.1021/acs.jnatprod.4c00082
- eISSN
- 1520-6025
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- J Nat Prod
- Schlüsselwörter
- Humans
- Anti-Inflammatory Agents
- Biological Products
- Lactones
- Molecular Structure
- Stereoisomerism
- Macrolides
- Sprache
- eng
- Country
- United States
- Paginierung
- 1131 - 1149
- Datum der Veröffentlichung
- 2024
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2024
- Titel
- Total Synthesis, Structure Reassignment, and Biological Evaluation of the Anti-Inflammatory Macrolactone 13-Hydroxy-14-deoxyoxacyclododecindione.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 87
Datenquelle: PubMed
- Beziehungen:
- Eigentum von