Novel PKC inhibitory analogs of balanol with replacement of the ester functionality

✍ Scribed by G. Erik Jagdmann Jr.; Jean M. Defauw; Yen-Shi Lai; Heidi M. Crane; Steven E. Hall; John A. Buben; Hong Hu; Paul A. Gosnell

• Book ID: 103983060
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 236 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00344-s

✦ Synopsis

Balanol ((-)-!) is a potent protein kinase inhibitory natural product isolated from the fungus Vertici/lium ba/anoides. The presence of an ester functionality in this molecule has prompted concern over the metabolic stability of balanol, and has led to a search for active analogs lacking this moiety. The synthesis and serum stability for some of these is presented herein.

Balanol ((-)-1) is a potent protein kinase C (PKC) inhibitory natural product isolated from the fungus Verticil/ium ba/anoides. 2 PKC is a family of phospholipid-dependent serine/threoninespecific protein kinases involved in cellular growth control, regulation, and differentiation. 3 Activation of PKC is a key step in processes such as cellular proliferation and gene expression, 4 and the enzyme has been implicated in the progress of a number of diseases. 5 The presence of an