Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortis simplex, showing a submicromolar activity against chloroquine-resistant strains of Plasmodium falciparum. Using plakortin as a novel antimalarial hit, we have prepared a series of semisynthetic derivatives in order to gain insights into the structural requirements of simple 1,2-dioxanes for exhibiting antimalarial activity. Their synthesis, spectroscopic and computational analysis, and in vitro antimalarial activity are herein reported. Results obtained, besides confirming the crucial role of the cycloperoxide functionality, revealed other structural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ring conformation, and the absolute configuration of the stereogenic carbons on the 1,2-dioxane ring, when affecting the bioactive ring conformation.

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Three new (5–7) and two known (4 and 8) polyketide derivatives have been isolated from the Caribbean sponge Plakortis simplex. Their stereostructures have been determined by spectroscopic methods and chemical transformations that include Zn‐mediated reduction and Dess–Martin oxidation, and by application of Mosher’s method. The cycloperoxide derivatives plakortide Q (7) and compound 8 were evaluated for their in vitro antimalarial activity against chloroquine‐sensitive and chloroquine‐resistant strains of Plasmodium falciparum. The lower potency of these molecules relative to plakortin indicates that the change of configuration at C‐3 exerts negative effects on the antimalarial activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Opopanax chironium is a rich source of furano- and dihydrofuranocoumarins, whose accumulation in all plant parts and especially the roots is presumably responsible for the poisonous properties of the species. The presence of two distinct chemotypes was evidenced, with the one from Sicily affording the new dihydrofuranocoumarins 5d and 5e, while extracts from the Sardinian chemotype showed powerful apoptotic activity, which was traced to the prenylated furanocoumarins heraclenin (2a) and imperatorin (2b). Despite a close structural similarity, compounds 2a and 2b induced apoptosis in Jurkat leukemia cells in mechanistically different ways.

Investigation of the most polar fractions obtained from the organic extract of the Caribbean marine sponge Plakortis simplex has led to the isolation of three novel iodine‐containing tryptophan betaines structurally related to the known hypaphorine (5), which have been named plakohypaphorine A (2), B (3) and C (4). Their structures have been determined by spectroscopic methods. Isolation of compounds 2−4 is particularly remarkable since it represents the first finding of iodoindole derivatives in a natural source, either marine or terrestrial. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)