Strategies towards expansion of chemical space of natural product‑based compounds to enable drug discovery

  • Daniel Gedder Silva University of Sao Paulo. School of Pharmaceutical Sciences of Ribeirao Preto. Department of Pharmaceutical Sciences
  • Flavio da Silva Emery University of Sao Paulo. School of Pharmaceutical Sciences of Ribeirao Preto. Department of Pharmaceutical Sciences
Keywords: Chemical space, Natural products, Ring distortion, Fragment-based drug discovery, Diversityoriented synthesis, Chemical degradation

Abstract

Natural products (NPs) are an excellent source of biologically active molecules that provide many biologically biased features that enable innovative designing of synthetic compounds. NPs are characterized by high content of sp3 -hybridized carbon atoms; oxygen; spiro, bridged, and linked systems; and stereogenic centers, with high structural diversity. To date, several approaches have been implemented for mapping and navigating into the chemical space of NPs to explore the different aspects of chemical space. The approaches providing novel opportunities to synthesize NP-inspired compound libraries involve NP-based fragments and ring distortion strategies. These methodologies allow access to areas of chemical space that are less explored, and consequently help to overcome the limitations in the use of NPs in drug discovery, such as lack of accessibility and synthetic intractability. In this review, we describe how NPs have recently been used as a platform for the development of diverse compounds with high structural and stereochemical complexity. In addition, we show developed strategies aiming to reengineer NPs toward the expansion of NP-based chemical space by fragment-based approaches and chemical degradation to yield novel compounds to enable drug discovery.

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Published
2018-12-28
How to Cite
Silva, D., & Emery, F. (2018). Strategies towards expansion of chemical space of natural product‑based compounds to enable drug discovery. Brazilian Journal of Pharmaceutical Sciences, 54(Especial), e01004. https://doi.org/10.1590/s2175-97902018000001004
Section
Review