Total Synthesis and Biological Evaluation of the Tetramic Acid Based Natural Product Harzianic Acid and Its Stereoisomers

• Published in: Organic letters Vol. 17; no. 3; pp. 692 - 695
• Main Authors: Healy, Alan R, Vinale, Francesco, Lorito, Matteo, Westwood, Nicholas J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.02.2015; Amer Chemical Soc
• Subjects: acids; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal properties; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; chemical reactions; Chemistry; Chemistry, Organic; Hydroxybutyrates - chemical synthesis; Hydroxybutyrates - chemistry; Hydroxybutyrates - pharmacology; Letter; Molecular Structure; organic compounds; Physical Sciences; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Pyrrolidinones - chemistry; root growth; Science & Technology; Stereoisomerism; stereoisomers; synthesis; INHIBITOR; TRICHODERMA
• ISSN: 1523-7060; 1523-7052; 1523-7052
• DOI: 10.1021/ol503717r

The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey–Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.