New diterpenes from the marine pulmonate Trimusculus peruvianus

The family Trimusculidae produce labdane diterpenes, which differ in the degree and type of esterification with acetoxy and isovaleroyl ester, predominantly. In this article, we describe the isolation from the marine pulmonate Trimusculus peruvianus, collected on intertidal rocks of Chilean coasts, of two new labdane diterpenes closely related to the above mentioned characteristics. Their structures were determined by spectroscopic data and correspond to 6beta-hydroxy-labda-8, 13-dien-15-ol and 3, 19-isovaleroyl-6beta, 9alpha-dihydroxylabda-Delta(8,17), 13-dien-15-oic acid.     

NMR determination of the bioactive conformation of peloruside A bound to microtubules

We report here on the determination of the conformation of Peloruside A bound to biochemically stabilized microtubules, by using TR-NOESY NMR experiments. As a previous step, the conformation of the free molecule in water solution has also been deduced. Despite the large size of the ring, Peloruside A mainly adopts two conformations in water solution. A conformational selection process takes place, and the microtubules-bound conformer is one of those present in the water solution, different than that existing in chloroform medium. A model of the binding mode to tubulin has also been proposed, by docking the bioactive conformation of peloruside, which involves the alpha-tubulin monomer, in contrast with taxol, which binds to the beta-monomer.