Antascomicin B : a synthetic study

The Antascomicin series was discovered in a screening program aimed at discovering new immunosuppressants. The members of this series bear structural similarities to both Rapamycin and FK-506, and all form a complex with the binding protein FKBP12, a prerequisite for immunosuppressive activity for certain keto-amide macrolides. Whilst the antacomicins do not function as immunosuppressants themselves, non-immunosuppressive FKBP12 ligands have been shown to promote nerve growth in vitro and in vivo. Thus a full biological profile is required for a proper evaluation of the potential of this family. (Fig. 3726) Nevertheless, the complex polyketide structure of Antascomicin B, including both lactone and lactam functionalities, an all-equatorially substituted cyclohexane ring, 12 stereogenic centres and a masked 1,2,3-tricarbonyl unit, makes for an enticing synthetic target. The proposed strategy disconnects the molecule into the three fragments shown. Fragment synthesis and connection will be presented, along with the evolution of an elegant protocol developed within the group, to effect macrocyclisation and tricarbonyl formation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo