Total synthesis studies on macrocyclic pipecolic acid natural products: FK506, the antascomicins and rapamycin.
This chapter derives its inspiration from the challenges presented to total synthesis chemists, by a particular group of macrocyclic pipecolic acid natural products. Although there is considerable emphasis on the completed syntheses of the main characters (FK506 (1), the antascomycins (4 and 5) and rapamycin (7)), the overall complexity of the molecular problem has stimulated a wealth of new knowledge, including the development of novel strategies and the invention of new synthetic methods. The ingenious and innovative approaches to these targets have enabled new generations of analogues, and provided material to further probe the biology of these fascinating molecules. With pharmaceutical application as an immunosuppressant, as well as potential use for the treatment of cancer and neurodegenerative diseases, this family of natural products continues to inspire new and interesting science while providing solutions to healthcare problems of the world.
Maddess
Matthew L
ML
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Tackett
Miles N
MN
Ley
Steven V
SV
D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D001688:Biological Products; D010875:Pipecolic Acids; D020123:Sirolimus; D016559:Tacrolimus