Synthesis and Biological Activity of 25-Methoxy-, 25-Fluoro-, and 25-Azabrassinolide and 25-Fluorocastasterone: Surprising Effects of Heteroatom Substituents at C-25.

The CuCN-catalyzed addition of 2-propenylmagnesium bromide to (threo-2R,3S,5alpha,22R,23R,24S)-23,24-epoxy-6,6-(ethylenedioxy)-2,3-(isopropylidenedioxy)-26,27-dinorcholestan-22-ol (11a) afforded the corresponding Delta(25)-22,23-diol 12. This was converted into 25-methoxybrassinolide (7) by protection as the 22,23-acetonide 13, oxymercuration in methanol, Baeyer-Villiger oxidation, and deprotection. Similarly, the addition of pyridinium poly(hydrogen fluoride) to 13 and deprotection afforded 25-fluorocastasterone (8), which was converted into 25-fluorobrassinolide (9) by Baeyer-Villiger oxidation.