Concise, three-step enantioselective total synthesis of (4S,5S)-4-hydroxy-5-octylpyrrolidin-2-one, a colibactin pathway metabolite

We report the first synthesis of (4S,5S)-4-hydroxy-5-octylpyrrolidin-2-one, one of the colibactin pathway metabolites isolated and characterized in 2021. Our synthesis started from (S)-malimide, a chiral building block previously developed from our laboratory. The first five-step approach consists of a highly regioselective Grignard addition at C-2 of (S)-malimide, catalytic dehydration, catalytic cis-selective hydrogenation of enamide, and successive cleavages of N-PMB and O-benzyl groups. By telescoping three reactions into one step, an even concise, three-step enantioselective total synthesis of the title compound has been achieved. Through this first enantioselective total synthesis, full physical and spectral data of this natural product were obtained. [GRAPHICS]