Application of Pictet–Spengler Reaction to Indole-Based Alkaloids Containing Tetrahydro-β-carboline Scaffold in Combinatorial Chemistry

• Published in: ACS combinatorial science Vol. 19; no. 4; pp. 199 - 228
• Main Authors: Rao, R. Nishanth, Maiti, Barnali, Chanda, Kaushik
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.04.2017
• Subjects: Carbolines - chemical synthesis; Combinatorial Chemistry Techniques; Cyclization; Green Chemistry Technology; Indole Alkaloids - chemical synthesis; Stereoisomerism; Structure-Activity Relationship; indole-based alkaloids; privileged tetrahydro-β-carboline scaffolds; drug discovery; Pictet−Spengler reaction
• ISSN: 2156-8952; 2156-8944; 2156-8944
• DOI: 10.1021/acscombsci.6b00184

Indole-based alkaloids are well-known in the literature for their diverse biological properties. Polysubstituted optically active tetrahydro-β-carboline derivatives functionalized on C-1 position are the common structural motif in most of the indole-based alkaloids, as well as highly marketed drugs. The stereoselective Pictet–Spengler reaction is one of the currently most important synthetic techniques used for the preparation of these privileged tetrahydro-β-carboline scaffolds. To date, there are numerous research reports that have been published on the synthesis of the tetrahydro-β-carboline scaffold both on solid phase, as well as in solution phase. Moreover rapid growth has been observed for the enantioselective synthesis of tetrahydro-β-carboline scaffold using chiral organocatalysts. In this Review, efforts have been taken to shed light on the latest information available on different strategies to synthesize tetrahydro-β-carboline both on solid phase and in solution phase during the last 20 years. Furthermore, we believe that the present synthetic methodologies covered in this Review will help to improve the status of this privileged tetrahydro-β-carboline scaffold in its use for drug discovery.