Uncovering the Potent Antiviral Activity of the Sesterterpenoids from the Sponge Ircinia Felix Against Human Adenoviruses: from the Natural Source to the Total Synthesis.

Human Adenovirus (HAdV) infections in immunocompromised patients can result in disseminated diseases with high morbidity and mortality rates due to the absence of available treatments for these infections. The sponge Ircinia felix was selected for the significant anti-HAdV activity displayed by its organic extracts. Its chemical analysis yielded three novel sesterterpene lactams, ircinialactams J-L, along with three known sesterterpene furans which structures were established by a deep spectrometric analysis.

Enigmazole C: A Cytotoxic Macrocyclic Lactone and Its Ring-Opened Derivatives from a New Species of Sponge.

A new macrolide, enigmazole C (), and two additional analogues, enigmazoles E () and D (), were obtained from a new species of the genus as part of an ongoing discovery program at PharmaMar to study cytotoxic substances from marine sources. The structures were fully characterized by cumulative analyses of NMR, IR, and MS spectra, along with density functional theory computational calculations. All three of the new compounds feature an unusual 2,3-dihydro-4-pyran-4-one moiety, but only enigmazoles C () and D () showed cytotoxic activity in the micromolar range against A-549 (lung), HT-29 (colon), MDA-MB-231 (breast), and PSN-1 (pancreas) tumor cells.

Indium(III)-Catalyzed Stereoselective Synthesis of Tricyclic Frameworks by Cascade Cycloisomerization Reactions of Aryl 1,5-Enynes.

The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene ( and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed.

Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide.

The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety.