Bioactive tetramic acid metabolites

Abstract

Secondary metabolites containing the tetramic acid (2,4-pyrrolidine-2,4- dione) ring system have been known for almost half a century, and well before the parent system was synthesised. Although the first naturally occurring tetramic acids were identified because of their activity as antibiotics and/or mycotoxins, more recently tetramic acid-containing compounds have been found to display a remarkable diversity of biological activities. The often unusual and intricate substituents modifying the tetramic acid structural unit make the synthesis of these metabolites a challenging target. Recent studies has confirmed that these metabolites have a wide distribution and play a significant role in ecological interactions. They have been isolated from marine mollusks, sponges and cyanobacteria, terrestrial and marine microorganisms, particularly endophytic fungi. In an attempt to bring all these strands together, this review will consider the structure, chemistry, biosynthesis, bioactivity, distribution and ecology of this diverse group of metabolites.