Toward the asymmetric synthesis of the C17-C34 fragment of antascomicin B via an Ireland Claisen (ICR) and allylic diazene (ADR) rearrangement sequence

by Clay, David R.; McIntosh, Matthias C.

Antascomicin B is a member of a family of macrolides isolated from a strain of the gram-pos. bacterium, Micromonospora. It exhibits FKBP 12 binding activity as potent as rapamycin and FK506, but does not inhibit the proliferation of T-cells and, in fact, antagonizes the inhibitory activity of FK506 and rapamycin. We are currently engaged in the total synthesis of antascomicin B. Our approach will employ Ireland-Claisen and allylic diazene rearrangements to establish the C23, C26 and C27 stereocenters. We have recently published a racemic synthesis of an advanced model compd. that demonstrated the feasibility of the approach. This presentation will describe efforts toward asym. synthesis of the C17-C34 fragment. The Ireland Claisen rearrangement precursor will be prepd. using either an enzymic desymmetrization or a RuIIcatalyzed hydrogen transfer.