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Authors: Lugiņina, Jevgeņija
Linden, Martin
Bazulis, Māris
Kumpiņš, Viktors
Mishnev, Anatoly
Popov, Sergey A.
Golubeva, Tatiana S.
Waldvogel, Siegfried R.
Shults, Elvira E.
Turks, Māris
Title: Electrosynthesis of stable betulin-derived nitrile oxides and their application in synthesis of cytostatic lupane-type triterpenoid-isoxazole conjugates
Online publication date: 15-Nov-2022
Year of first publication: 2021
Language: english
Abstract: 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 15N 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 (GI50) concentrations up to 11 μm, while being harmless to immortalized human fibroblasts hTERT (GI50 >100 μm).
DDC: 540 Chemie
540 Chemistry and allied sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 09 Chemie, Pharmazie u. Geowissensch.
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: European journal of organic chemistry
Pages or article number: 2557
Publisher: Wiley-VCH
Publisher place: Weinheim
Issue date: 2021
ISSN: 1099-0690
Publisher DOI: 10.1002/ejoc.202100293
Appears in collections:JGU-Publikationen

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