Preparation of synthons for the synthesis of protein kinase C inhibitors from rebeccamycin.

Bioorganic & Medicinal Chemistry Letters
1992.0

Abstract

An efficient process to obtain aglycons, useful for the preparation of protein kinase C inhibitors, was developed from Rebeccamycin, an antitumor antibiotic isolated from Sacchurotrix aerocolonigenes. The activation of protein kinase C is one of the earliest events in the cascade of signal transduction pathways leading to a large variety of cellular responses among which are gene expression and prolifemtion and muscle contractioni. Therefore, PKC inhibitors may be useful as drugs in the treatment of cardiac and vascular diseases or cancers. Among the PKC inhibitors which interact with the adenosine triphosphate binding site are microbial metabolites possessing an indoloearba;role unit as staurosporine2, UCN-01 and 023, RK-286C4, K-252 a,bs, TAN-999 and 1030Ae (figure 1) isolated from different strains of Streptomyces or Nocardiopsis species. Their inhibitory activity is shown in table I.

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