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

Abstract

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 GABA(A) receptor, cytotoxic, and brassinolide activity, which reached in some cases the same range as their nonfluorinated analogues.

Cross-metathesis of allylcarboranes with O-allylcyclodextrins

“…Only catalysis by Hoveyda–Grubbs 2 nd generation catalyst gave the desired product 3 in 14% yield. The suitability of Hoveyda–Grubbs 2 nd generation catalyst for cross-metathesis reactions was consistent with the previously observed results [5–8]. Further tuning of the reaction conditions showed that the best yields were obtained by carrying out the reaction in toluene at 120 °C for 16 h (Scheme 1).…”

“…Recently, we have shown that metathesis of various terminal alkenes with perfluoroalkylpropenes constitutes a simple and efficient approach for the synthesis of wide array of perfluoroalkylated compounds [4]. This methodology was then applied for the synthesis of perfluoroalkylated analogs of brassinosteroids [5], 17α-perfluoroalkylestradiols [6], perfluoroalkylcyclodextrins [7], and perfluoroalkylcarboranes [8]. Successful execution of these reactions prompted us to study also cross-metathesis of allylcarboranes with O -allylcyclodextrins as a route to carborane-cyclodextrin conjugates.…”

Steroid plant hormones: Effects outside plant kingdom

“…4). A norcastasterone hepta-fluorinated derivative 18 was the only analogue of this type which exhibited a slight cytotoxicity (IC 50 = 35.3 lM against CEM cell line) [120]. A distinct cytotoxicity (IC 50 = 7-15.8 lM) against MGC 7901 (human gastric carcinoma), HeLa (human cervical carcinoma) and SMMC 7404 (human liver carcinoma) cells displayed cholestane lactones 19 and 20 [121].…”

Computational study of productive and non-productive cycles in fluoroalkene metathesis

“…In contrast to common alkenes, the metathesis of fluoroalkenes has attracted far less attention [ 23 ]. Fluorinated modifications have mostly concentrated on the side chain of the vinyl group [ 24 – 27 ] or applications of 2-fluoroalkenes [ 28 – 30 ]. As an exception, the reaction of the Grubbs 2 nd generation catalyst with 1,1-difluoroethene gave an isolable difluoromethylene-containing ruthenium complex with very poor catalytic activity [ 31 ] and the analogous reaction of 1-fluoroalkene formed a fluoromethylene-containing complex with low catalytic activity [ 32 – 33 ].…”