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
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8089
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	European journal of organic chemistry 2021 17
Pages or article number:	2557 2577
Publisher:	Wiley-VCH
Publisher place:	Weinheim
Issue date:	2021
ISSN:	1099-0690
Publisher DOI:	10.1002/ejoc.202100293
Appears in collections:	JGU-Publikationen