Structure of FD-895 revealed through total synthesis.
The total synthesis of FD-895 was completed through a strategy that featured the use of a tandem esterification ring-closing metathesis (RCM) process to construct the 12-membered macrolide and a modified Stille coupling to append the side chain. These studies combined with detailed analysis of all four possible C16-C17 stereoisomers were used to confirm the structure of FD-895 and identify an analog with an enhanced subnanomolar bioactivity.
Department of Chemistry and Biochemistry, University of Calfornia, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
Reymundo
R
Villa
Alexander L
AL
Mandel
Brian D
BD
Jones
James J
JJ
La Clair
Michael D
MD
Burkart
D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism
C091810:FD 895; D018942:Macrolides