A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease

A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease Научная публикация

Журнал

Journal of Fluorine Chemistry
ISSN: 0022-1139

Вых. Данные

Год: 2023, Том: 271, Номер статьи : 110189, Страниц : 10 DOI: 10.1016/j.jfluchem.2023.110189

Ключевые слова

Sinomenine, Hydroxycodeinone, Trifluoromethylation, Ruppert–Prakash reagent, Carbonylation-cross-coupling reaction, SARS-CoV-2, Main viral protease 3CLpro

Авторы

Finke Anastasija O. , Krasnov Vyacheslav I. , Rybalova Tatyana V. , Chirkova Varvara Yu. , Belenkaya Svetlana V. , Volosnikova Ekaterina A. , Shcherbakov Dmitry N. , Shults Elvira E.

Организации

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences
2	Novosibirsk State University
3	Altai State University
4	State Research Center of Virology and Biotechnology VECTOR

Информация о финансировании (1)

Российский Научный Фонд

23-73-00077

A catalytic trifluoromethylation of stereoisomeric 6-ketomorphinans using Ruppert–Prakash reagent and tetrabutylammonium fluoride (TBAF) was studied. 14β-Hydroxycodeinone, 4-O-methylsinomenine and 1-iodo-4-Omethylsinomenine provided good to excellent yields of the corresponding 6-trifluoromethylated compounds. The new morphinan derivative (6-deoxo-1-iodo-6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol) was involved in some catalytic transformations for introduction of additional substituent on C-1 position of the morphinan core. The palladium-catalyzed carbonylation–cross coupling reaction of 1-iodo-derivative with phenylacetylene in the presence of PdCl2-(1-Ad)2PBn catalytic system and Mo(CO)6 as a source of carbon monoxide in MeCN proceeds with high selectivity with the formation of alkynyl ketone as the main product. The cyclocondensation with acetamidine hydrochloride afforded the arylpyrimidine – 6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol hybrid compound. The action of the dehydration system (SOCl2-Py-DMAP) on 6-deoxo-6α-(trifluoromethyl)-4-Omethylsinomenin-6β-ol have led to the formation оf 8β‑chloro-6,7-didehydro-6-(trifluoromethyl)morphinan which showed inhibition the main viral protease (3CLpro) of SARS-CoV-2 at IC50 value of 25 μM.

Finke A.O. , Krasnov V.I. , Rybalova T.V. , Chirkova V.Y. , Belenkaya S.V. , Volosnikova E.A. , Shcherbakov D.N. , Shults E.E.
A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease
Journal of Fluorine Chemistry. 2023. V.271. 110189 :1-10. DOI: 10.1016/j.jfluchem.2023.110189 WOS РИНЦ OpenAlex

Поступила в редакцию:	14 авг. 2023 г.
Принята к публикации:	17 сент. 2023 г.
Опубликована online:	22 сент. 2023 г.

Web of science:	WOS:001082082200001
РИНЦ:	63336239
OpenAlex:	W4386975163

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