Synthesis and Biological Studies of Simplified Analogues of Lyngbyatoxin A: Use of an Isoxazoline-Based Indole Synthesis. Quest for Protein Kinase C Modulators

Efficient synthetic routes to optically active analogues of lyngbyatoxin A, a potent activator of protein kinase C, have been devised starting from L-valine methyl ester. Access to the indole nucleus of these molecules is gained through the nitrile oxide based annelation of an aromatic ring to a pyrrole ring. The biological action of several of the intermediates and analogues prepared during the course of these studies on protein kinase C activity is also presented.