A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease Full article
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Journal of Fluorine Chemistry
ISSN: 0022-1139 |
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| Output data | Year: 2023, Volume: 271, Article number : 110189, Pages count : 10 DOI: 10.1016/j.jfluchem.2023.110189 | ||||||||
| Tags | Sinomenine, Hydroxycodeinone, Trifluoromethylation, Ruppert–Prakash reagent, Carbonylation-cross-coupling reaction, SARS-CoV-2, Main viral protease 3CLpro | ||||||||
| Authors |
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| Affiliations |
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Funding (1)
| 1 | Российский Научный Фонд | 23-73-00077 |
Abstract:
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.
Cite:
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
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
Dates:
| Submitted: | Aug 14, 2023 |
| Accepted: | Sep 17, 2023 |
| Published online: | Sep 22, 2023 |
Identifiers:
| Web of science | WOS:001082082200001 |
| Elibrary | 63336239 |
| OpenAlex | W4386975163 |