New sources of chemical diversity inspired by biosynthesis: rational design of a potent epothilone analogue.
A concise total synthesis of (S)-14-methoxyepothilone D has been accomplished. (S)-14-Methoxyepothilone D represents a conceptually novel example of polyketide analogue design based on an alternative biogenetic pattern of extender units. The significant biological activity observed for this compound provides a foundation to support studies designed to prepare derivatives of this type through fermentation of genetically engineered organisms expressing the epothilone PKS gene cluster.
Frein
Jeffrey D
JD
Department of Chemistry and Biochemistry and the Walther Cancer Research Center University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, Indiana 46556-5670, USA.
Taylor
Richard E
RE
Sackett
Dan L
DL
D045744:Cell Line, Tumor; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C544839:(S)-14-methoxyepothilone; D034261:Epothilones; D018942:Macrolides; C426624:epothilone C; C114026:desoxyepothilone B