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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