Cyclopropane Fatty Acid Derivatives: Biosynthesis, Function and Total Synthesis

INTRODUCTION Cyclopropane-containing natural products are very unique owing to their unusual bonding and inherent ring strain (27.5 kcal/mol). 1 This strained ring has been found in naturally occurring terpenes, steroids, amino acids, fatty acids, alkaloids, and nucleic acids. For example, chrysanthemic acid derivatives, produced in plants via isoprenoid pathway are precursors to potent insecticides. Many cyclopropane-containing non-natural compounds also have important biological activities. An example is Cipro, a powerful anti-anthrax drug. Cyclopropane fatty acids (CFA) comprise an interesting family of primary and secondary metabolites (Figure 1). Most CFA derivatives contain only one threemembered ring, and occur as phospholipids 1 in bacterial membranes. Biosynthetically, they are derived from the corresponding unsaturated fatty acid (UFA) phospholipids. The formation of the cyclopropane ring is catalyzed by CFA synthase. The genetics and physiological role of CFA synthase are currently under active investigation.