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We recently proposed 3-methoxy-4-methoxycarbonyl-1,2-dioxanes 3 as promising scaffolds enabling access to potential antimalarial drugs. We present here an optimized two-step synthesis of 3 characterized by high yields, simple work-up procedures and high diastereoselectivity allowing us to readily prepare 3 on multigram scale. The versatility of the 1,2-dioxane scaffold was demonstrated by our generation of a new family of 1,2-dioxane-4-carboxamides 8a–h and the realization of their in vitro activities against chloroquine-sensitive (D10) and chloroquine-resistant (W2) P. falciparum strains. In particular, one of these amides (8e), displayed antimalarial activity on par with the natural product lead plakortin and was 5-fold more active than its methyl ester analogue 3. Structure–activity relationship (SAR) analysis supported by DFT calculations revealed that, for this family of compounds, alkyl substituents at C6 dictate, in large part, the degree of antimalarial activity. This finding contrasts those previously observed for the ester series.

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)

Three new iodinated tryptophan derivatives, plakohypaphorines D−F (4−6), have been isolated from the Caribbean sponge Plakortis simplex. Their structures have been determined by applying spectroscopic methods and microwave-assisted selective dehalogenation. Compound 5 is the first naturally occurring triiodinated indole, while compound 6 is a unique metabolite because it possesses both chlorine and iodine atoms on the indole nucleus. We have evaluated the antihistamine activity of the whole series of plakohypaphorines A−F, but only the diiodinated analogues proved to be active: they display a specific antagonism of the noncompetitive type. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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)

Plakortethers A−G (4−10) represent a new class of plakortin-related metabolites containing a trisubstituted tetrahydrofuran ring. They have been isolated from the Caribbean sponge Plakortis simplex and their stereostructures fully characterized by a combination of spectroscopic data and chemical evidence, based on a three-step conversion of the cycloperoxide plakortin into plakortether B (5). Plakortethers A (4), B (5), D (7), and E (8) exhibited selective cytotoxicity against the RAW 264-7 cell line (murine macrophage).

The fresh latex of cultivated E. resinifera Berg. is a convenient source of the ultrapotent vanilloid resiniferatoxin, and a transesterification-reesterification procedure that substantially alleviates the hazards associated with the direct isolation of this obnoxious diterpenoid has been developed. Various known phorboid constituents of the diterpenoid fraction were obtained in pure form and have been spectroscopically characterized for the first time, while the non-diterpenoid fraction of the latex gave, besides some common triterpenoids, three new bisnorsesquiterpenes of the dihydroionol type. The structures of these compounds were established through a combination of spectroscopic data and chemical reactions.

Two novel norlanostane triglycosides, ectyoplasides A (1) and B (2), have been isolated from the methanolic extracts of the Caribbean sponge Ectyoplasiaferox (Raspaliidae, Axinellida). Their structures have been established by extensive application of high-resolution FABMS and two-dimensional NMR techniques, supported by chemical and enzymatic degradation methods. Ectyoplasides A and B have been shown to possess identical sugar chains (composed of two β-galactose units and one α-arabinose unit), but to differ in their aglycone moieties, which possess nortriterpene skeletons with an unprecedented substitution pattern on ring A. Ectyoplasides A and B show moderate cytotoxic activity when tested in vitro towards various cell lines

The cover picture shows the formula of cannabimovone, a cannabinoid with a rearranged terpenoid skeleton isolated from an industrial strain of hemp derived from the old Italian variety Carmagnola. The trade of this exceptionally tall plant (up to 5–6 m) from the homonymous Piedmontese town at the foot of the Monviso mountain (see the painting at the right) to Marseille in France was at the origin of the French revolutionary song and dance la Carmagnole. The picture shows the cultivation of Carmagnola hemp at the foot of the Vesuvio, exemplifying the collaboration between the Italian groups from Campania and Piedmont who report the discovery of cannabimovone on p. 2067 ff. The authors acknowledge Mrs. Maria Rosa Gaude for the painting, Assocanapa (Carmagnola) and Dr. Nicola Ghietti for the pictures and their help, and Dr. Alberto Massarotti for the cover page design.