Tetraene macrolides, synthesis

Migrastatin (192) (Scheme 37) is a novel macrolide natural product that displays an inhibitory effect on the migration of human tumor cells. After an RCM-based synthesis of the 14-membered macrolide core of 192 [94], Danishefsky also achieved the first total synthesis of the natural compound [95], using the fully functionalized tetraene 191 as the metathesis precursor. Under the conditions shown in Scheme 37, the ring-closing step proceeded (E)-selectively with exclusive participation of the two terminal double bonds in 191, delivering only the ( , ,Z)-trienyl arrangement present in 192. 

Thomas et al. [90] prepared two 17-membered macrocyclic tetraenes that are possible precursors of the natural product lankacidin C in this case, a trisubstituted vinyl iodide was involved, and the amount of Pdjdbaj required was relatively high (30%). Toshima et al. [91] reported a highly stereoselective total synthesis of the macrolide antibiotic concanamycin F again, intermolecular and intramolecular vinyl-vinyl couphngs were used. WhUe liCl was used as an additive in the former, it was replaced by DIPEA in the latter. In a recent pubUcation [49], Toshima et al. 

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