||The overall purpose of this project has been to develop an effective inhibitor of Acyl-CoA cholesterol O -acyltransferase (ACAT), based upon the fundamental structure of the phytotoxin, helminthosporol. The research specifically focused on total synthetic studies to furnish desisopropyl-prehelminthosporol and desmethylene-prehelminthosporol, two minimized analogs of the natural product. The proposed synthetic routes were based on a strategy of formation of [3.2.1]-bicyclooctanone core common to the helminthosporols, followed by specific adaptations to afford each target. A principal portion of the research has been invested in a development of an effective route towards a construction of the core, relying essentially upon a sequence of silyl-directed Nazarov cyclization, Darzens condensation and divinylcyclopropane rearrangement. This was followed by studies emphasizing on the development of specific routes aimed to furnish our targets.