TOTAL SYNTHESIS OF BALANOL AND DESIGNED ANALOGS

The total synthesis of balanol, a potent protein kinase C inhibitor is olated From the fungus Verticillium balanoides, is described, The hexa hydroazepine fragment was prepared from D-serine through a sequence of reactions including the diastereoselective allylboration of derived a mino aldehyde and a base-induced 7-exo-tet ring closure as key steps. The benzophenone fragment was secured through the initial coupling of the two functionalised aromatic components through an ester linkage, f ollowed by intramolecular nucleophilic attack of an aryl lithium deriv ative to form the desired ketone bridge, After coupling of the two bal anol domains, the adoption of benzyl-derived protecting groups for the latent functionalities then allowed the liberation of balanol in a si ngle step by catalytic hydrogenolysis. Finally, the newly developed sy nthetic strategy was applied to the synthesis of a variety of designed balanol analogues for biological evaluation.