Autoren:	Lugiņina, Jevgeņija Linden, Martin Bazulis, Māris Kumpiņš, Viktors Mishnev, Anatoly Popov, Sergey A. Golubeva, Tatiana S. Waldvogel, Siegfried R. Shults, Elvira E. Turks, Māris
Titel:	Electrosynthesis of stable betulin-derived nitrile oxides and their application in synthesis of cytostatic lupane-type triterpenoid-isoxazole conjugates
Online-Publikationsdatum:	15-Nov-2022
Erscheinungsdatum:	2021
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	540 Chemie 540 Chemistry and allied sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 09 Chemie, Pharmazie u. Geowissensch.
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8089
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	European journal of organic chemistry 2021 17
Seitenzahl oder Artikelnummer:	2557 2577
Verlag:	Wiley-VCH
Verlagsort:	Weinheim
Erscheinungsdatum:	2021
ISSN:	1099-0690
DOI der Originalveröffentlichung:	10.1002/ejoc.202100293
Enthalten in den Sammlungen:	JGU-Publikationen