Eight new sesterterpenoids, alotaketals D (8) and E (9), ansellones D (10), E (11), F (12), and G (13), and anvilones A (14) and B (15), have been isolated from extracts of the marine sponge Phorbas sp. collected in Howe Sound British Columbia, and their structures have been elucidated by analysis of NMR and MS data. Ansellone F (12) contains a rare 1,2-3,4-bis-epoxydecalin substructure. Anvilones A (14) and B (15) have an unprecedented tetracylic anvilane terpenoid carbon skeleton. Using a cell culture model of latent HIV-1 infection, ansellone A (3), alotaketal D (8), and anvilone A (14) were found to induce HIV proviral gene expression similar to the control compound prostratin (1), while the known sesterterpenoid alotaketal C (2), isolated from the same extract, was more potent and gave a stronger response than prostratin (1). Like prostratin (1), all of the Phorbas sesterterpenoids with latency reversal agent properties appear to activate protein kinase C signaling.
Ansellone A (1) has been isolated from the dorid nudibranch Cadlina luteomarginata and the sponge Phorbas sp. It has the new "ansellane" sesterterpenoid carbon skeleton, and it activates the cAMP signaling pathway.
Four new sesterterpenoids, ansellone B (4), phorbadione (5), secoepoxyansellone A (6), and alotaketal C (7), have been isolated from specimens of the sponge Phorbas sp. collected in British Columbia. Ansellone B (4) has an unprecedented heterocyclic skeleton featuring an oxocane ring, and secoepoxyansellone A (6) is the first example of the degraded "secoansellane" sesterterpenoid carbon skeleton. Alotaketal C (7) is an activator of cAMP signaling in HEK cells.
Clionamines A-D (1- 4), new aminosteroids that modulate autophagy, have been isolated from South African specimens of the sponge Cliona celata. Clionamine D (4) has an unprecedented spiro bislactone side chain.
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