Spirocyclisation of phytoalexin 1-methoxybrassinin in the presence of Grignard reagents

The anti-cancer properties of naturally occurring (2 R , 3 R )-(−)-1-methoxyspirobrassinol methyl ether ( I ) and their synthetic amino or piperidyl analogues II inspired us to study the synthesis of new target compounds III with a C—C bond in the 2-position of indole rather than a C—N or C—O bond ( I or II respectively). The goal was achieved via electrophilic-nucleophilic 3,2-difunctionalisation of 1-methoxybrassinin ( IV ) in the presence of bromine and the Grignard reagent leading to the formation of cis - and trans -C—C analogues of I . Finally, the anti-cancer activities of the new compounds were measured and compared with I and II in order to show the importance of a heteroatom in the 2-substituted indole on the anti-cancer activity of spirobrassinols.