Abstract
In the interdisciplinary research field of chemical biology and drug discovery, diversity-oriented synthesis (DOS) has become indispensable in the construction of novel small-molecule libraries rich in skeletal and stereochemical diversity. DOS aims to populate the unexplored chemical space with new potential bioactive molecules via forward synthetic analysis. Since the introduction of this concept by Schreiber, DOS has evolved along with many significant breakthroughs. It is therefore important to understand the key DOS strategies to build molecular diversity with maximized biological relevancy. Due to the length limitations of this mini review, we briefly discuss the recent DOS plans using build/couple/pair (B/C/P) and ring-distortion strategies for the synthesis of major biologically relevant target molecules like natural products and their related compounds, macrocycles, and privileged structures.
Highlights
Small molecules play an indispensable role in the fields of drug discovery and chemical biology due to their unique features compared to biologics, polymers, and nanoparticles (Samanen, 2013)
This can be attributed to advances in chemical biology and drug discovery disclosing novel targets beyond conventional druggable proteins, such as DNA (Hurley, 2002), RNA (Lieberman, 2018; Warner et al, 2018), protein–protein interactions (PPIs) (Scott et al, 2016), and protein– RNA interactions (PRIs) (Hentze et al, 2018), among others
Privileged structures, which are common structural motifs in a vast number of bioactive natural products and therapeutic agents, contain novel structural features that secure a high biological relevancy (Evans et al, 1988). In this mini review, we present recent advancements in the B/C/P and ring-distortion diversity-oriented synthesis (DOS) approaches in the context of natural products, natural product-like compounds, macrocycles, and privileged structures
Summary
Reviewed by: Raphaël Frédérick, Université Catholique de Louvain, Belgium Steven Ballet, Vrije Universiteit Brussel, Belgium Laurent Commeiras, Aix-Marseille Université, France. Strategies in Diversity-Oriented Synthesis: Build/Couple/Pair and Ring-Distortion. In the interdisciplinary research field of chemical biology and drug discovery, diversity-oriented synthesis (DOS) has become indispensable in the construction of novel small-molecule libraries rich in skeletal and stereochemical diversity. DOS aims to populate the unexplored chemical space with new potential bioactive molecules via forward synthetic analysis. It is important to understand the key DOS strategies to build molecular diversity with maximized biological relevancy. Due to the length limitations of this mini review, we briefly discuss the recent DOS plans using build/couple/pair (B/C/P) and ring-distortion strategies for the synthesis of major biologically relevant target molecules like natural products and their related compounds, macrocycles, and privileged structures
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