Planta Med 2013; 79 - PC5
DOI: 10.1055/s-0033-1348561

Semi-Synthesis of a Biologically Inspired Library of Natural Product Mimics, from the Lipophilic Marine Natural Product β-Gorgonene

B Pearce 1, R Kerr 1, 2
  • 1Department of Chemistry, University of Prince Edward Island, Charlottetown, PE, C1A 4P3
  • 2Department of Biomedical Sciences, Atlantic Veterinary College, Charlottetown PE, C1A 4P3

Inspired by ilimaquinone and other biologically active sesquiterpenes, we have transformed a highly lipophilic, non-drug-like, marine natural product (gorgonene), available as a by-product from the purification of pseudopterosins, into a library of more drug-like derivatives. Our strategy utilizes semi-synthesis to attach suitable structures such as substituted aromatics and heteroaromatics to the gorgonene scaffold to increase its drug-likeness and mimic natural product structures in biological systems. Several synthetic techniques are being explored to incorporate these interesting substructures in a minimum number of steps. The first strategy focuses on skeletal rearrangements and 2+3 cycloaddition. The second involves ozonolysis of gorgonene followed by introduction of structures using carbonyl chemistry. Biotransformation is being used as a third strategy to selectively oxidize synthetically inaccessible carbons on the saturated backbone to facilitate further transformations. The PTP1B (potential therapeutic target for treatment of type 2 diabetes) and cytotoxic activity of the synthesized compounds will be discussed as well as some unexpected and interesting reactivity we have observed in the 1,5-diene system present in our starting scaffold, β-gorgonene.