Matinkhoo et al. devised strategies to surmount three synthetic hurdles to give α-amanitin in 2018.[12] First, enantioselective synthesis of solid phase peptide synthesis-compatible (2S,3R,4R)-4,5-dihydroxyisoleucine was afforded in 11 steps from 2-(benzyloxy)acetaldehyde. Two key stereochemistry-defining steps include Brown crotylation at (3R,4R)-positions, and asymmetric Strecker amino acid synthesis at the (2S)-α carbon.[13] Secondly, chemoselective inner ring closure by fluorocyclization between 6-hydroxytrytophan and cysteine was achieved by intra-annular Savige-Fontana reaction.