Solid phase synthesis of complex natural products and libraries thereof.
Natural products have served as an important source of medicinal compounds and pharmaceutical leads over the last century. Within the last 10 years, significant interest has developed in applying combinatorial chemistry techniques to the study of natural products and their biological activities. In this review, we examine several representative efforts wherein natural product skeletons have been constructed or immobilized on solid support and subsequently derivatized, giving rise to analog libraries useful in understanding the structure-activity relationships of the parent natural product. Issues such as target selection, library design, linker development, automation, and library characterization are addressed.
Nicolaou
K C
KC
Department 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
Pfefferkorn
J A
JA
D000470:Alkaloids / Q000138:chemical synthesis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000975:Antioxidants / Q000138:chemical synthesis; D020650:Combinatorial Chemistry Techniques; D003516:Cycloparaffins / Q000138:chemical synthesis; D004224:Diterpenes; D034261:Epothilones; D004968:Estrogens, Non-Steroidal / Q000138:chemical synthesis; D018942:Macrolides / Q000138:chemical synthesis; D008956:Models, Chemical; D010452:Peptide Biosynthesis; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis*; D012643:Selenium / Q000737:chemistry; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000138:chemical synthesis; D015025:Zearalenone / Q000138:chemical synthesis
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D003516:Cycloparaffins; D004224:Diterpenes; D034261:Epothilones; D004968:Estrogens, Non-Steroidal; D018942:Macrolides; D019151:Peptide Library; D010455:Peptides; C109552:sarcodictyin A; C093787:epothilone A; D015025:Zearalenone; D014640:Vancomycin; D012643:Selenium; C031021:muscone