Small molecule natural products in the discovery of therapeutic agents: the synthesis connection.
Natural products have been a rich source of agents of value in medicine. They have also inspired, at various levels, the fashioning of nonnatural agents of pharmaceutical import. Hitherto, these nonnatural derivatives have been primarily synthesized by manipulating the natural product. As a consequence of major innovations in the subscience of synthetic methodology, the capacity of synthesis to deal with molecules of considerable complexity has increased dramatically. In this paper, we show by example some total syntheses which draw from strategy-enabling advances in methodology. Moreover, we show how these capabilities can be used to discover and develop new agents of potential pharmaceutical value without recourse to the natural product itself.
Wilson
Rebecca M
RM
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Danishefsky
Samuel J
SJ
D001685:Biological Factors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D009930:Organic Chemicals / Q000138:chemical synthesis* / Q000627:therapeutic use*
D001685:Biological Factors; D009930:Organic Chemicals