Chiral cruciferous phytoalexins: Preparation, absolute configuration, and biological activity

Abstract

Synthesized by an efficient one-pot spirocyclization method, two chiral cruciferous phytoalexins, 1-methoxyspirobrassinin ( 2) and 1-methoxyspirobrassinol methyl ether ( 4a), were prepared through optical resolution using the chiral HPLC method of corresponding racemates. The absolute configuration of natural (+)- 2 was elucidated as R by using the direct comparison of ECD and VCD spectra with those of known ( S)-(−)-spirobrassinin ( 1). Another chiral phytoalexin, (−)- 4a, had its absolute configuration 2 R,3 R elucidated through the comparison of observed and calculated VCD. Interestingly, the absolute configurations of natural ( S)-(−)-spirobrassinin ( 1) and ( R)-(+)-1-methoxyspirobrassinin ( 2) were opposite of each other, even though their structures are almost similar, with the exception of an N-methoxy group. A significant difference in the antiproliferative activity between (2 R,3 R)-(−) and (2 S,3 S)-(+)- 4a was observed.