Occurrence of Enantioselectivity in Nature: The Case of (S)-Norcoclaurine.

This review article is aimed at providing a monographic overview on (S)-norcoclaurine (NC) alkaloid from three diverse points of view, collected all together for the first time: 1) the synthetic one, where the compound is seen as a target chiral molecule to be obtained in the highest optical purity and as a starting point for the development of biocatalytic asymmetric syntheses of tetrahydroisoquinoline alkaloids; 2) the chromatographic one, which addresses the HPLC separation of the two NC enantiomers; and 3) the biochemical one, for which a thorough understanding of the topology and mechanism of action of norcoclaurine synthase (NCS) enzyme is still a matter of debate. Special emphasis on the most recent studies in the field is given by discussing the results published by the main research groups who are working on NC and NCS.

The Pictet-Spengler Reaction Still on Stage.

Today, in spite of being older than a century (born in 1911), the Pictet-Spengler two component reaction (PS-2CR) is still one of the most popular reactions, not only for the synthesis of tetrahydroisoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), or more complex structures containing these two privileged moieties, but also for the construction of novel scaffolds, available for structure-activity relationship (SAR) studies and/or for combinatorial libraries targeted at drug discovery. The prominence of the P-S cyclization is brought about by the inheritance from analogous enzyme-catalyzed reactions of the biogenetic pathways of natural products, mainly indole alkaloids, with a broad range of biological activities. This knowledge has been the starting point for the biomimetic synthesis or the bio-engineering production of pharmacologically important drugs.