An expedient synthesis of the proposed biosynthetic precursor of the oxepine natural product, janoxepin

An efficient synthetic route to the putative biosynthetic intermediate of the anti-plasmodial natural product janoxepin is described. This novel enamine-containing pyrazino[2,1-b]quinazoline-3,6-dione, and its synthetic precursors, should be of value in studies to elucidate the biosynthetic pathway leading to the oxepine family of natural products. The cornerstones of the synthesis are amide coupling, pyrazino[2,1-b]quinazoline-3,6-dione construction and aldol introduction of the enamine. (C) 2012 Elsevier Ltd. All rights reserved.