Biocatalytic asymmetric formation of tetrahydro-β-carbolines

Abstract

Strictosidine synthase triggers the formation of strictosidine from tryptamine and secologanin, thereby generating a carbon–carbon bond and a new stereogenic center. Strictosidine contains a tetrahydro-β-carboline moiety—an important N-heterocyclic framework found in a range of natural products and synthetic pharmaceuticals. Stereoselective methods to produce tetrahydro-β-carboline enantiomers are greatly valued. We report that strictosidine synthase from Ophiorrhiza pumila utilizes a range of simple achiral aldehydes and substituted tryptamines to form highly enantioenriched (ee >98%) tetrahydro-β-carbolines via a Pictet–Spengler reaction. This is the first example of aldehyde substrate promiscuity in the strictosidine synthase family of enzymes and represents a first step toward developing a general biocatalytic strategy to access chiral tetrahydro-β-carbolines.