First Total Synthesis of Staurosporine and ent-Staurosporine

摘要

Staurosporine was first isolated by Omura and colleagues from Streptomyces staurosporeus. Its configuration was recently revealed to be that shown in structure 1. Previously, structure 2, now known to be ent-staurosporine, had been assigned to Staurosporine. (See Chart 1.) Interest in Staurosporine at the biological level springs from its nanomolar inhibition of protein kinase C(PKC). Given the central role of protein phosphorylation in orchestrating the cell cycle, powerful inhibitors of PKC might be useful as antipro-liferative agents. Needless to say, high levels of tissue specificity in the delivery of a PKC inhibitor would be critical for its development as a drug.