Epothilones ring-closing olefin metathesis strategy

For the cyclization to the 16-membered macrolactone structure of epothilones C and D (= desoxyepothilones A and B, resp. [26]), three different strategies have been used successfully so far (1) Ring-closing olefin metathesis (RCM) between C12 and Cl3. RCM is a comparably new method in total synthesis and underwent enor-... 

The problems hindering the total synthesis of epothilones involve (1) stereoselective construction of C3, C6, C7, and C8 chiral centers, (2) synthesis of the thi-azole unit having a 15S-hydroxyl group, (3) construction of (12Z)-olefin, (4) macrocyclization, and (5) stereoselective epoxidation of (12Z)-olefin. The total syntheses of epothilones have been achieved via three strategies for the macrocyclization (Fig. 9) (1) macroaldolization, (2) ring-closing olefin metathesis, and... 

The RCM strategy was applied to the synthesis of epothilone E (5c) [143i] (Scheme 83). The vinyl iodide 576, which was synthesized through C12-C13 ring-closing olefin metathesis, was subjected to the Stille coupling with 577 to afford 578. The epoxidation of the C12-C13 double bond in 578 completed the total synthesis of epothilone E (5c). 

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