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.