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On the Remarkable Antitumor Properties of Fludelone: How We Got There
Author(s) -
Rivkin Alexey,
Chou TingChao,
Danishefsky Samuel J.
Publication year - 2005
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200461751
Subject(s) - epothilones , drug discovery , context (archaeology) , chemistry , epothilone , function (biology) , combinatorial chemistry , computational biology , total synthesis , drug development , small molecule , nanotechnology , biochemical engineering , drug , stereochemistry , biochemistry , pharmacology , biology , materials science , engineering , microbiology and biotechnology , paleontology
Small‐molecule natural products are presumably often biosynthesized with a view to optimizing their ability to bind to strategic proteins or other biomolecular targets. Although the ultimate setting in which a drug must function may be very different, the use of such natural products as lead compounds can serve as a significant head start in the hunt for new agents of clinical value. Herein we reveal the synergistic relationship between chemical synthesis and drug optimization in the context of our research program around the epothilones: how synthesis led to the discovery of more‐potent epothilone derivatives, and discovery inspired the development of new synthetic routes, thus demonstrating the value of target‐directed total synthesis in the quest for new substances of material clinical benefit.