Method for synthesizing epothilones and epothilone analogs
View Patent ↗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.
1. A compound according to the formula:
where R substituents independently are H, lower alkyl, or a protecting group, R 1 is
R 2 and R 3 independently are H or lower aliphatic groups, R 4 substituents independently are selected from the group consisting of lower aliphatic groups, and R 5 and R 6 independently are H or lower aliphatic.
2. The compound according to claim 1 having the formula
3. The compound according to claim 1 having the formula
4. The compound according to claim 1 having the formula