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Solid phase synthesis of complex natural products and libraries thereof.
K C Nicolaou1, J A Pfefferkorn
1Department of Chemistry, and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@scripps.edu
Biopolymers
|January 5, 2002
Summary
Natural products are key to drug discovery. Combinatorial chemistry is now used to create diverse natural product analog libraries for understanding structure-activity relationships.
Area of Science:
- Medicinal Chemistry
- Natural Products Chemistry
- Drug Discovery
Background:
- Natural products have historically been a vital source of medicinal compounds and pharmaceutical leads.
- Recent advancements have focused on applying combinatorial chemistry to natural product research.
- This approach aims to enhance the exploration of their biological activities.
Purpose of the Study:
- To review representative efforts in applying combinatorial chemistry to natural product skeletons.
- To highlight the creation of analog libraries for structure-activity relationship (SAR) studies.
- To discuss key considerations in developing these libraries.
Main Methods:
- Construction or immobilization of natural product scaffolds on solid support.
- Derivatization of immobilized scaffolds to generate analog libraries.
- Examination of target selection, library design, linker development, automation, and characterization.
Main Results:
- Successful generation of diverse natural product analog libraries.
- Demonstration of the utility of these libraries in SAR studies.
- Identification of critical factors for effective library development.
Conclusions:
- Combinatorial chemistry offers a powerful strategy for natural product analog library synthesis.
- These libraries are instrumental in elucidating structure-activity relationships of natural products.
- Further research and development in automation and library characterization are beneficial.