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Antimalarial Isocyano and Isothiocyanato Sesquiterpenes with Tri- and Bicyclic Skeletons from the Nudibranch Phyllidia ocellata

Author:
White, Andrew M., Pierens, Gregory K., Skinner-Adams, Tina, Andrews, Katherine T., Bernhardt, Paul V., Krenske, Elizabeth H., Mollo, Ernesto, Garson, Mary J.
Source:
Journal of natural products 2015 v.78 no.6 pp. 1422-1427
ISSN:
1520-6025
Subject:
Plasmodium falciparum, X-ray diffraction, antimalarials, biochemical pathways, inhibitory concentration 50, isothiocyanates, sesquiterpenoids, spectral analysis
Abstract:
Five new isocyano/isothiocyanato sesquiterpenes (1–5) with tri- or bicyclic carbon skeletons have been characterized from Australian specimens of the nudibranch Phyllidia ocellata. Spectroscopic analyses at 900 MHz were informed by DFT calculations. The 1S, 5S, 8R configuration of 2-isocyanoclovene (1) was determined by X-ray crystallographic analysis of formamide 6. A biosynthetic pathway to clovanes 1 and 2 from epicaryolane precursors is proposed. Isocyanides 1, 2, and 4 showed activity against Plasmodium falciparum (IC₅₀ 0.26–0.30 μM), while isothiocyanate 3 and formamide 6 had IC₅₀ values of >10 μM.
Agid:
5498230