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Review
. 2020 May 27;6(5):622-635.
doi: 10.1021/acscentsci.9b00916. Epub 2020 Apr 22.

Late-Stage Diversification of Natural Products

Benke Hong  1   2   3   4   5 , Tuoping Luo  1   3   5   6 , Xiaoguang Lei  1   2   3   4   5
Affiliations
Review

Late-Stage Diversification of Natural Products

Benke Hong et al. ACS Cent Sci. .

Abstract

Late-stage diversification of natural products is an efficient way to generate natural product derivatives for drug discovery and chemical biology. Benefiting from the development of site-selective synthetic methodologies, late-stage diversification of natural products has achieved notable success. This outlook will outline selected examples of novel methodologies for site-selective transformations of reactive functional groups and inert C-H bonds that enable late-stage diversification of complex natural products. Accordingly, late-stage diversification provides an opportunity to rapidly access various derivatives for modifying lead compounds, identifying cellular targets, probing protein-protein interactions, and elucidating natural product biosynthetic relationships.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Natural products in human medicine.
Scheme 1
Scheme 1. (A) Late-Stage Site-Selective Diversification of Vancomycin. (B) MIC Values (μg/mL) for Vancomycin Derivatives. (C) Selected Natural Products for Late-Stage Diversification via Site-Selective Transformation of Reactive Functional Groups
Scheme 2
Scheme 2. (A) Late-Stage Diversification of (+)-Sclareolide (27) via Selective C–H Functionalization. (B) Chemical Environment of (+)-Sclareolide
Scheme 3
Scheme 3. (A) (+)-Artemisinin Based Antimalaria Drugs. (B) Modification of (+)-Artemisinin (3) via Late-Stage Diversification. (C) Phase I and Phase II Metabolism of Artemisinins. (D) Selected Examples of Artemisinin Analogues with Improved Metabolic Stability
Scheme 4
Scheme 4. (A) Pleuromutilin-Based Antibiotics. (B) Modification of (+)-Pleuromutilin (61) via Late-Stage Diversification
Scheme 5
Scheme 5. (A) Chemical Probe Synthesis of Eupalmerin Acetate (EuPA) (82). (B) Target Identification of Anticancer Natural Product Eupalmerin Acetate (EuPA) (82)
Scheme 6
Scheme 6. (A) Biogenetic Hypothesis of Jungermannenone-Type Diterpenoids. (B) Late-Stage Photoinduced Skeleton Rearrangements of Terpenoids
Scheme 7
Scheme 7. Modulating Protein–Protein Interactions by Late-Stage Derivatization of FK506
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References

    1. Nicolaou K. C.; Montagnon T.. Molecules That Changed the World; Wiley-VCH, 2008.
    1. Corey E. J.; Kürti L.; Czako B.. Molecules and Medicine; Wiley-VCH, 2007.
    1. Newhouse T.; Baran P. S.; Hoffmann R. W. The economies of synthesis. Chem. Soc. Rev. 2009, 38, 3010–3021. 10.1039/b821200g. - DOI - PMC - PubMed
    1. Koehn F. E.; Carter G. T. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discovery 2005, 4, 206–220. 10.1038/nrd1657. - DOI - PubMed
    1. Newman D. J.; Cragg G. M. Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod. 2016, 79, 629–661. 10.1021/acs.jnatprod.5b01055. - DOI - PubMed