threo-Pentonic acid, 2,5-anhydro-3,4-dideoxy-4-[[[(5S)-3-(3,5-difluorophenyl)-5-ethenyl-4,5-dihydro-5-isoxazolyl]carbonyl]amino]-, methyl ester

Icafolin and its methyl ester derivative, icafolin-methyl, are synthesised through a stereoselective multi-step process that centers on constructing a 4-hydroxy-2-isoxazoline scaffold. The key intermediate is formed via a cyclocondensation reaction between 3,5-difluoronitromethane and alpha-formylbutyrolactone, producing a spirocyclic nitronate structure. This intermediate undergoes further transformations, including Grieco dehydration, which is optimised using continuous flow techniques for scalability and diastereoselectivity. The final steps involve amide bond formation and methyl esterification, yielding icafolin-methyl with a controlled isomeric ratio of (2R,4R) and (2S,4S) stereoisomers.

Inhibition of tubulin.

Herbicide