Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar;7(2):119-136.
doi: 10.1016/j.apsb.2016.06.003. Epub 2016 Nov 25.

The modification of natural products for medical use

Zongru Guo  1
Affiliations
Review

The modification of natural products for medical use

Zongru Guo. Acta Pharm Sin B. 2017 Mar.

Abstract

Drug innovation is characterized by painstaking molecular-level syntheses and modifications as the basic components of research and development. Similarly, natural products are chemically tailored and modified based upon their structural and biological properties. To some extent, the modification of natural products is quite different from de novo structure-based drug discovery. This review describes the general strategies and principles for the modification of natural products to drugs, as illustrated by several successful medicines that originated from natural products.

Keywords: Artemisinin; Indirubin; Multi-dimensional optimization; Natural products; Structure–acitivity reactivity; Synthesis.

PubMed Disclaimer

Figures

fx1
Graphical abstract
Fig. 1
Figure 1
The general features of natural products.
Fig. 2
Figure 2
Modification strategies for natural products.
Fig. 3
Figure 3
Simplifying structures from halichondrin B to eribulin.
Fig. 4
Figure 4
Simplifying structures from myriocin to fingolimod.
Fig. 5
Figure 5
Simplifying structures from schizandrin C to DDB and bicyclol.
Fig. 6
Figure 6
Simplifying structures from lovastatin to “statin” drugs.
Fig. 7
Figure 7
Simplifying structures from trichostatin A to vorinostat.
Fig. 8
Figure 8
Simplifying structures from vancomycin to telavancin and dalbavancin.
Fig. 9
Figure 9
Simplifying structures from enkephalin to eluxadoline.
Fig. 10
Figure 10
The optimization from enkephalin to eluxadoline.
Fig. 11
Figure 11
Simplifying structures from himbacine to vorapaxar.
Fig. 12
Figure 12
Structures of compounds 46 and 47.
Fig. 13
Figure 13
Structures of compounds 49.
Fig. 14
Figure 14
Pyridine-containing analogs.
Fig. 15
Figure 15
Simplifying structures from phlorizin to canagliflozin and other “gliflozins”.
Fig. 16
Figure 16
Simplifying structures from retinoic acid to tamibarotene.
Fig. 17
Figure 17
Simplifying structures from patupilone to ixabepilone.
Fig. 18
Figure 18
Simplifying structures from artemisinin to dihydtoartemisinin, artemether, artesunate, and artether.
Fig. 19
Figure 19
Simplifying structures from indirubin to meisoindigo.
Scheme 1
Scheme 1
The final coupling reactions of eribulin.
Scheme 2
Scheme 2
The concise scheme of total synthesis of himacidine.
Scheme 3
Scheme 3
Synthetic scheme of compound 48.
Scheme 4
Scheme 4
Synthetic route of pyridine-containing analogs.
Scheme 5
Scheme 5
The semisynthetic route of ixabepilone.
Scheme 6
Scheme 6
The total synthesis of ixbepilone.
Scheme 7
Scheme 7
The brief synthetic route of eravacycline.
Scheme 8
Scheme 8
The synthetic route of houttuynium.
See this image and copyright information in PMC

References

    1. Hopkins A.L., Groom C.R., Alex A. Ligand efficiency: a useful metric for lead selection. Drug Discov Today. 2004;9:430–431. - PubMed
    1. Aicher T.D., Buszek K.R., Fang F.G., Forsyth C.J., Jung S.H., Kishi Y. Total synthesis of halichondrin B and norhalichondrin B. J Am Chem Soc. 1992;114:3162–3164.
    1. Towle M.J., Salvato K.A., Budrow J., Wels B.F., Kuznetsov G., Aalfs K.K. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001;61:1013–1021. - PubMed
    1. Yu M.J., Zheng W.J., Seletsky M.B. From micrograms to grams: scale-up synthesis of eribulin mesylate. Nat Prod Rep. 2013;30:1158–1164. - PubMed
    1. Fujita T., Inoue K., Yamamoto S., Ikumoto T., Sasaki S., Toyama R. Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot. 1994;47:208–215. - PubMed