Asymmetric Synthesis of (R)-1-Alkyl-Substituted Tetrahydro-ß-carbolines Catalyzed by Strictosidine Synthases.

ABSTRACT: Stereoselective methods for the synthesis of tetrahydro-ß-carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C-C coupling through a Pictet-Spengler reaction of tryptamine and secologanin to exclusively form the (S)-configured tetrahydro-ß-carboline (S)-strictosidine. Investigating the biocatalytic Pictet-Spengler reaction of tryptamine with small-molecular-weight aliphatic aldehydes revealed that the strictosidine synthases give unexpectedly access to the (R)-configured product. Developing an efficient expression method for the enzyme allowed the preparative transformation of various aldehydes, giving the products with up to >98?% ee. With this tool in hand, a chemoenzymatic two-step synthesis of (R)-harmicine was achieved, giving (R)-harmicine in 67?% overall yield in optically pure form.

SUBMITTER: Pressnitz D 

PROVIDER: S-EPMC6146909 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other