Synthesis and biological evaluation of conformationally constrained bicyclic and tricyclic balanol analogues as inhibitors of protein kinase C

A series of conformationally constrained bicyclic (20–25 and 28) and tricyclic (26 and 27) balanol analogues was prepared and evaluated as inhibitors of protein kinase C (PKC). Of special interest are bicyclic balanol analogues 20 and 24 and the tricyclic analogue 26, which not only retain the nanomolar activity for most PKC isozymes, but also display good selectivity over c-AMP dependent protein kinase (PKA).