Marine natural meroterpenes from Aplidium conicum: structures, synthesis and pharmacology

Meroterpenes are compounds of mixed biosynthesis, mostly quinones or hydroquinones bonded with a terpenoid portion. In the marine environment, these secondary metabolites are isolated mainly from brown algae, but other sources include microorganisms, soft corals and invertebrates. Among marine ascidians, they have been found almost exclusively in species belonging to the genus Aplidium, which have been the source of a vast array of prenyl-quinone, -hydroquinone, -chromene, and/or -chromane derivatives, either linear or cyclic, originated from intra- and inter-molecular cyclizations and/or rearrangements, thus giving macrocyclic or policyclic skeletons, often linked to amino acids or taurine residues. We have isolated from several collections of A. conicum a large group of unique meroterpenes. One of these compound has been used as model compound for the synthesis of synthetic analogues in which the prenyl chain is replaced by other alkyl chains; both the synthetic analogues and the natural metabolite were subjected to pharmacological screenings and were shown to possess interesting biological effects, depending on the nature and the length of side chain linked to the benzoquinone ring and, mainly, on its position respect to the dioxothiazine ring. Our studies revealed exemplify the potential of a natural product to qualify as lead structure for medicinal chemistry campaigns, affording simplified analogues with better bioactivity and easier to synthesize.