Enantioselective Brønsted Acid Catalysis as a Tool for the Synthesis of Natural Products and Pharmaceuticals

Abstract

Synthesis of biologically active molecules (whether at laboratory or industrial scale) remains a highly appealing area of modern organic chemistry. Nowadays, the need to access original bioactive scaffolds goes together with the desire to improve synthetic efficiency, while reducing the environmental footprint of chemical activities. Long neglected in the field of total synthesis, enantioselective organocatalysis has recently emerged as an environmentally friendly and indispensable tool for the construction of relevant bioactive molecules. Notably, enantioselective Brønsted acid catalysis has offered new opportunities in terms of both retrosynthetic disconnections and controlling stereoselectivity. The present report attempts to provide an overview of enantioselective total or formal syntheses designed around Brønsted acid-catalyzed transformations. To demonstrate the versatility of the reactions promoted and the diversity of the accessible motifs, this Minireview draws a systematic parallel between methods and retrosynthetic analysis. The manuscript is organized according to the main reaction types and the nature of newly-formed bonds.

On the Basicity of Organic Bases in Different Media

“…Acids and bases serve as catalysts in a variety of chemical and biochemical transformations, playing a crucial role in the processes of life. Their significance in chemistry is not limited to the disciplines of physical organic and synthetic chemistry but extends to chemical engineering and industrial applications . Also, the fact that almost 80 % of all drugs contain ionisable groups underlines the indispensability of knowing p K a values in medicinal chemistry and understanding the factors that influence them for effective drug design.…”

Deep Eutectic Mixtures as Reaction Media for the Enantioselective Organocatalyzed α-Amination of 1,3-Dicarbonyl Compounds

“…Due to accessibility, as well as green considerations, enantioselective organocatalysis has proved to be one of the most efficient approach towards the synthesis of drugs and natural products [39][40][41][42][43]. In particular, the organocatalytic functionalization of indolin-3-one has been recently studied since this type of heterocycles are commonly found in an ample range of biologically active natural alkaloids [44][45][46][47][48].…”

Enantioselective Organocatalyzed a-Amination of 1,3-Dicarbonyl Compounds in Deep Eutectic Mixtures

“…This electrophile was used for further studies. Due to accessibility as well as green considerations, enantioselective organocatalysis has proved to be one of the most efficient approach towards the synthesis of drugs and natural products [37][38][39][40][41]. In…”