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Peroxide Natural Products from Plakortis zyggompha and the Sponge Association Plakortis halichondrioidesXestospongia deweerdtae: Antifungal Activity against Cryptococcus gattii

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journal contribution
posted on 09.02.2016 by Matthew T. Jamison, Doralyn S. Dalisay, Tadeusz F. Molinski
Cryptococcus gattii is a human pathogen and causative agent of a pernicious, sometimes fatal, disseminated fungal disease. Investigation of antifungal extracts of the marine sponge association Plakortis halichondrioidesXestospongia deweerdtae and the sponge Plakortis zyggompha from the Bahamas led to the discovery and isolation of 6-epi-7,8-dihydroplakortide K (1), plakortide AA (2), and three new plakinic acids, N–P (46; unstable 1,2-dioxolanes bearing benzyl-substituted conjugated dienes), along with known plakinic acids L, K, and M. Chiroptical comparisons and DFT calculations of 13C NMR chemical shifts were used to assign the absolute stereostructure of 4. The stereospecific base-promoted rearrangement–saponification of 1 to 10 was briefly investigated and showed tight kinetic control and stereospecific formation of the new C-2 stereocenter with inversion at C-3. Plakinic acid M and plakortides 9 and 11 exhibited antifungal activity against C. gattii (MIC90 = 2.4 to 36 μM), but plakinic acids N–P were inactive under the same conditions.