Towards the Synthesis of the C22-C34 Fragment of Antascomicin B

by Clay, David; McIntosh, Matt

Antascomicin B is a member of a family of macrolides isolated from a strain of the gram-pos. bacterium, Micromonospora sp. 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 inhib iitory 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 C22-C34 fragment using enzymic desymmetrization to a meso-diol to prep. the requisite precursor to the Ireland-Claisen rearrangement.