title: The Pictet-Spengler Reaction Still on Stage.
abstract: 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. The long-lasting life of the P-S reaction depends on the discovery of its multiple facets, the modifications of its parameters and components, as well as the continuous renovation of solutions for the challenging stereochemical outcome of the transformation. This paper deals with an updated visit to the P-S reaction aiming to find the threads of the story without forgetting the numerous facets of the prism. It is organized as a theater piece, with a prologue and the main scene (namely, Act 1) where the readers can follow the parade of the two above-mentioned very recurring motifs (namely, THIQ and THBC) by moving from one step to another (a cyclization, an intramolecular attack, a stereoselective passage) to find the way out of the labyrinth of the P-S reaction.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ingallina
authors.forename: Ilaria
authors.initials: I
authors.lastname: D'Acquarica
authors.forename: Giuliano
authors.initials: G
authors.lastname: Delle Monache
authors.forename: Francesca
authors.initials: F
authors.lastname: Ghirga
authors.forename: Deborah
authors.initials: D
authors.lastname: Quaglio
authors.forename: Patrizio
authors.initials: P
authors.lastname: Ghirga
authors.forename: Simone
authors.initials: S
authors.lastname: Berardozzi
authors.forename: Violeta
authors.initials: V
authors.lastname: Markovic
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le A. Moro 5, 00185 Roma, Italy. bruno.botta@uniroma1.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Botta
mesh_terms: D057005:Bioengineering; D019759:Carbon-Nitrogen Lyases / Q000378:metabolism*; D003500:Cyclization; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D026121:Indole Alkaloids; D019759:Carbon-Nitrogen Lyases; C022684:strictosidine synthetase