Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

Iakovenko, Roman O; Kazakova, Anna N; Muzalevskiy, Vasiliy M; Ivanov, Alexander Yu; Boyarskaya, Irina A; Chicca, Andrea; Petrucci, Vanessa; Gertsch, Jürg; Krasavin, Mikhail; Starova, Galina L; Zolotarev, Andrey A; Avdontceva, Margarita S; Nenajdenko, Valentine G; Vasilyev, Aleksander V (2015). Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands. Organic & biomolecular chemistry, 13(33), pp. 8827-8842. Royal Society of Chemistry 10.1039/c5ob01072a

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4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Chicca, Andrea; Petrucci, Vanessa and Gertsch, Jürg

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1477-0520

Publisher:

Royal Society of Chemistry

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

01 Mar 2016 13:56

Last Modified:

01 Mar 2016 13:56

Publisher DOI:

10.1039/c5ob01072a

PubMed ID:

26186675

BORIS DOI:

10.7892/boris.75961

URI:

https://boris.unibe.ch/id/eprint/75961

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