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

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

Журнал

European Journal of Organic Chemistry
ISSN: 1434-193X , E-ISSN: 1099-0690

Вых. Данные

Год: 2021, Том: 2021, Номер: 17, Страницы: 2557-2577 Страниц : 21 DOI: 10.1002/ejoc.202100293

Ключевые слова

1; 3-Dipolar cycloaddition; Electrochemical oxidation; Isoxazole; Lupeol; Nitrile oxide

Авторы

Luginina Jevgenija ¹ , Linden Martin ² , Bazulis Maris ¹ , Kumpins Viktors ¹ , Mishnev Anatoly ³ , Popov Sergey A. ⁴ , Golubeva Tatiana S. ⁵ , Waldvogel Siegfried R. Siegfried R. ² , Shults Elvira E. ⁴ , Turks Maris ¹

Организации

1	(Данные Web of science) RigaTech Univ, Fac Mat Sci & Appl Chem, P Valdena Str 3, LV-1007 Riga, Latvia
2	(Данные Web of science) Johannes Gutenberg Univ Mainz, Dept Chem, Duesbergweg 10-14, D-55128 Mainz, Germany
3	(Данные Web of science) Latvian Inst Organ Synth, Aizkraukles Str 21, LV-1006 Riga, Latvia
4	(Данные Web of science) Novosibirsk Organ Chem Inst, Academician Lavrentjev Ave 9, Novosibirsk 630090, Russia
5	(Данные Web of science) Inst Cytol & Genet, Fed Res Ctr, Acad Lavrentyev Ave 10, Novosibirsk 630090, Russia

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 3 beta-lupane-3,28-diol. Nitrile oxides were characterized by N-15 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(50)) concentrations up to 11 mu m, while being harmless to immortalized human fibroblasts hTERT (GI(50) >100 mu m).

Luginina J. , Linden M. , Bazulis M. , Kumpins V. , Mishnev A. , Popov S.A. , Golubeva T.S. , Waldvogel Siegfried R. S.R. , Shults E.E. , Turks M.
Electrosynthesis of Stable Betulin-Derived Nitrile Oxides and their Application in Synthesis of Cytostatic Lupane-Type Triterpenoid-Isoxazole Conjugates
European Journal of Organic Chemistry. 2021. V.2021. N17. P.2557-2577. DOI: 10.1002/ejoc.202100293 WOS Scopus РИНЦ

Web of science	WOS:000664259700028
Scopus	2-s2.0-85108268004
РИНЦ	46901182
OpenAlex	W3153368075