Synthesis of Fluorinated Brassinosteroids Based on Alkene Cross-Metathesis and Preliminary Biological Assessment

• Published in: Journal of medicinal chemistry Vol. 52; no. 18; pp. 5753 - 5757
• Main Authors: Eignerová, Barbara, Slavíková, Barbora, Buděšínský, Miloš, Dračínský, Martin, Klepetářová, Blanka, Št’astná, Eva, Kotora, Martin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.09.2009; Amer Chemical Soc
• Subjects: Alkenes - chemistry; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biological Assay; Brassinosteroids; Cell Line, Tumor; Chemical control; Chemistry, Medicinal; Cholestanols - pharmacology; Drug Discovery; Fundamental and applied biological sciences. Psychology; Gabaergic and benzodiazepinic system; General aspects; Halogenation; Humans; Life Sciences & Biomedicine; Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Parasitic plants. Weeds; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phytopathology. Animal pests. Plant and forest protection; Rats; Rats, Wistar; Receptors, GABA-A - metabolism; Science & Technology; Steroids - chemical synthesis; Steroids - chemistry; Steroids - metabolism; Steroids - pharmacology; Steroids, Heterocyclic - pharmacology; Weeds; MEDICINAL CHEMISTRY; ANTICANCER; ANALOGS; BRASSICA-NAPUS; PART; ALLOPREGNANOLONE; OLEFIN METATHESIS; PERFLUOROALKYL IODIDES; DERIVATIVES; EFFICIENT; Antineoplastic agent; Steroid; Ligand; Saturated compound; Metathesis; Cytotoxicity; Oxygen heterocycle; Structure activity relation; Plant growth substance; Oxidation; Mammary gland; Chemical synthesis; Tumor cell; Human; Haloalkylation; Haloalcohol; Hydroxylation; Lactone; In vitro; Glass transition temperature; Baeyer Villiger reaction; Brassinosteroid; Biological fixation; Cell line; Affinity; Fluorine Organic compounds; Gabaergic receptor A; Ethylenic compound; Glycol
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/jm900495f

Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one-step double dihydroxylation to provide intermediates that after Baeyer−Villiger oxidation afforded the target compounds. Biological activity of the prepared analogues was tested in GABAA receptor, cytotoxic, and brassinolide activity, which reached in some cases the same range as their nonfluorinated analogues.