A method for making epothilones and epothilone analogs is described, as are novel
compounds made by the method. One embodiment of the method was used to synthesize
epothilone B by a convergent approach that entailed Wittig coupling of an ylide
derived from phosphonium bromide with an aldehyde. The former was prepared from
propargyl alcohol by a nine-step pathway which installed both trisubstituted double
bonds with clean Z configuration. Macrolactonization of a resulting seco acid provided
the following intermediate diene epothilone analog. Selective saturation of the
9,10-olefin and subsequent epoxidation provided epothilone B.
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