Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)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.Publisher PDFPeer reviewe

Terretonins E and F, Inhibitors of the Mitochondrial Respiratory Chain from the Marine-Derived Fungus Aspergillus insuetus

Supporting Information Available: 1D and 2D NMR spectra for terretonins E and F. This material is available free of charge via the Internet at http://pubs.acs.org.[EN] Two new meroterpenoids, terretonins E and F (1, 2), together with three known compounds, aurantiamine (3), linoleic acid, and uridine, were isolated as fermentation products of the marine-derived fungus Aspergillus insuetus, which was associated with the sponge Petrosia ficiformis. Structures of all isolates were elucidated employing spectroscopic methods, mainly by two-dimensional NMR techniques. Compounds 1-3 showed activity as inhibitors of the mammalian mitochondrial respiratory chain.We acknowledge ICB and ITQ NMR Service (D. Melck and E. Mateos) and E. Estornell and V. Romero for biological assay support. We would like to thank the R&D&I Linguistic Assistance Office, Universidad Politecnica de Valencia (Spain), for granting financial support for the linguistic revision of this paper. This work has been supported through European Social Fund (ESF).López Gresa, MP.; Cabedo Escrig, N.; Gonzalez-Mas, MC.; Ciavatta, ML.; Avila, C.; Primo Millo, J. (2009). Terretonins E and F, Inhibitors of the Mitochondrial Respiratory Chain from the Marine-Derived Fungus Aspergillus insuetus. Journal of Natural Products. 72(7):1348-1351. doi:10.1021/np900085nS1348135172