Electrosynthesis of Stable Betulin‐Derived Nitrile Oxides and their Application in Synthesis of Cytostatic Lupane‐Type Triterpenoid‐Isoxazole Conjugates

Publication type:
Journal article
Metadata:
Abstract
<jats:title>Abstract</jats:title><jats:p>Novel lupane‐type triterpenoid‐isoxazole conjugates were designed by direct placing of isoxazole linker at C(17) of triterpenoid. The suggested synthetic sequence demonstrates successful combination of electro‐organic synthesis and conventional approaches. TEMPO‐mediated electrooxidation of betulin to betulinal was developed and optimized at boron‐doped diamond anodes with potassium acetate as inexpensive supporting electrolyte. Betulinal‐derived oxime was further selectively electro‐oxidized at a graphite anode to nitrile oxide, which proved to be stable and isolable species. The same reaction sequence was performed with 3β‐lupane‐3,28‐diol. Nitrile oxides were characterized by <jats:sup>15</jats:sup>N NMR and X‐ray crystallography. The isolable nitrile oxides allowed creation of isoxazole library by 1,3‐dipolar cycloaddition reactions with various alkynes. Some of the title conjugates exhibit cytostatic properties against breast cancer cell line MCF7, glioblastoma multiform cell line U‐87 MG and lung carcinoma cell line A549 with growth inhibition (GI<jats:sub>50</jats:sub>) concentrations up to 11 μ<jats:sc>m</jats:sc>, while being harmless to immortalized human fibroblasts hTERT (GI<jats:sub>50</jats:sub> &gt;100 <jats:sc>μm</jats:sc>).</jats:p>
Autoren
  • Jevgeņija Lugiņina
  • Martin Linden
  • Māris Bazulis
  • Viktors Kumpiņš
  • Anatoly Mishnev
  • Sergey A Popov
  • Tatiana S Golubeva
  • Siegfried R Waldvogel
  • Elvira E Shults
  • Māris Turks
DOI
10.1002/ejoc.202100293
eISSN
1099-0690
ISSN
1434-193X
Ausgabe der Veröffentlichung
17
Zeitschrift
European Journal of Organic Chemistry
Sprache
en
Online publication date
2021
Paginierung
2557 - 2577
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/ejoc.202100293
Datum der Datenerfassung
2023
Titel
Electrosynthesis of Stable Betulin‐Derived Nitrile Oxides and their Application in Synthesis of Cytostatic Lupane‐Type Triterpenoid‐Isoxazole Conjugates
Ausgabe der Zeitschrift
2021

Data source: Crossref

Other metadata sources:
Author's licence
CC-BY
Autoren
  • Jevgeņija Lugiņina
  • Martin Linden
  • Māris Bazulis
  • Viktors Kumpiņš
  • Anatoly Mishnev
  • Sergey A Popov
  • Tatiana S Golubeva
  • Siegfried R Waldvogel
  • Elvira E Shults
  • Māris Turks
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • JGU-Publikationen
Resource version
Published version
DOI
10.1002/ejoc.202100293
File(s) embargoed
false
Open access
true
ISSN
1099-0690
Ausgabe der Veröffentlichung
17
Zeitschrift
European journal of organic chemistry
Schlüsselwörter
  • 540 Chemie
  • 540 Chemistry and allied sciences
Sprache
eng
Open access status
Open Access
Paginierung
2557 - 2577
Datum der Veröffentlichung
2021
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/8104
Herausgeber
Wiley-VCH
Datum der Datenerfassung
2022
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Zugang
Public
Titel
Electrosynthesis of stable betulin-derived nitrile oxides and their application in synthesis of cytostatic lupane-type triterpenoid-isoxazole conjugates
Ausgabe der Zeitschrift
2021

Files

electrosynthesis_of_stable_be-20221115115020172.pdf

Data source: OPENSCIENCE.UB

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