Progress toward the synthesis of Antascomicin B

by Hutchison, John M.; Clay, David R.; Rivero, Juliette; McIntosh, Matthias C.

The antascomicins are a small family of macrolides isolated in China from soil bacteria of the genus Micromonospora that exhibits very strong binding to FKBP12. The most potent of these, antascomicin B, binds with an IC50 of 0.7 nM, equiv. to that of FK-506 and rapamycin. The C21-C34 fragment of the potent FKBP12-binding macrolide antascomicin B was prepd. using Ireland-Claisen and allylic diazene rearrangements to establish the C26/C27 and the C23 stereocenters, resp. The fragment possesses 7 of the 11 relevant stereocenters contained in the natural product.