Synthesis and Biological Evaluation of Fungal Bioregulators of Sterol Biosynthesis

Abstract

Corey published a leading paper in 196 7 demonstrating that 2, 3-iminosqualene inhibited the cyclization of squalene-oxide to lanosterol in a cell-free system¹. In the interim years between then and this seventh international plant lipid symposium, four groups-one each in the United States², Canada³ another in France⁴ and Italy⁴, have firmly established the mechanistic and biological importance of using this and structurally related molecules, e.g. 25-azasteroids⁵, to interfere with fungal sterol biosynthesis which results in diminished growth response. Industry and biotechnology firms have followed suit in recent years designing analogous inhibitors^{6, 7} which they believe may have potential promise in plant protection. On the premise that specific N-isopentenoids induce alterations in sterol biosynthesis which in turn may create a pathologic state in the structure and function of membranes of pathogenic fungi, we began a chemical synthesis program in 1984 by preparing blockers targeted at fungal lipid biosynthesis.