Use of the kinetically controlled Pictet–Spengler reaction in the asymmetric synthesis of indole alkaloids: formal syntheses of (–)-ajmaline, (–)-koumine, (–)-taberpsychine, (–)-koumidine and (–)-suavoline

Abstract

By employing the kinetically controlled Pictet–Spengler reaction L-tryptophan was used as the chiral starting material for the synthesis of the cis-1,3-disubstituted tetrahydro-β-carboline 14a. Protection of the two nitrogens and subsequent cyclisation/decarboxylation led to generation of the bridged ketone (–)-(7c), which was shown to be optically pure within our detection limits (ee >95%). Simple protecting group modifications gave access to (–)-7a and (–)-7b, and constituted formal synthesis of (–)-ajmaline, (–)-koumine, (–)-taberpsychine, (–)-koumidine and (–)-suavoline. These results demonstrate that such alkaloids with the correct absolute configuration are accessible in a stereocontrolled manner from L-tryptophan.