Studies toward the C22-C34 fragment of antascomicin B

by Hutchison, John M.; Williams, David; Wolfenberg, Peter; McIntosh, Matt C.

The antascomicins are a small family of macrolides that possesses sub-nanomolar FKBP12 binding activity, but antagonize the binding of immunosuppressants rapamycin and FK-506. Synthesis of the C22-C34 fragment of antascomicin B will involve a directed hydrogenation to establish the C29 stereocenter and a diastereoselective acyclic 1,3-reductive transposition to establish the remote C23 stereocenter. Installation of the C26,C27 stereocenters is achieved via an Ireland-Claisen rearrangement.