TOTAL SYNTHESIS OF (-)-BALANOL AND (-BALANOL())

Two total syntheses of the potent protein kinase C inhibitory fungal m etabolite balanol are described. In the first approach, the core amino hydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiom ers of balanol. In the second approach, an efficient silicon-mediated cyclization of(2S,3R)-3-hydroxylysine followed by reduction provided t he azepane subunit in enantiomerically pure form. The sterically conge sted benzophenone subunit was assembled from two highly substituted ar omatic precursors by way of an anionic home-Fries rearrangement.