Procedimiento para la preparación de merosesquiterpenos mediante cicloadición de Diels Alder de dienos derivados de diterpenos

Número de publicación: ES2563602 B1. Número de solicitud: 201400746.Universidad de GranadaUniversité Abdelmalek Essaâd

First Enantiospecific Syntheses of Marine Merosesquiterpenes Neopetrosiquinones A and B: Evaluation of Biological Activity

The first enantiospecific syntheses of neopetrosiquinones A (<b>6</b>) and B (<b>7</b>), two merosesquiterpenes isolated from the deep-water sponge <i>Neopetrosia</i> cf. <i>proxima</i>, from the labdane diterpene <i>trans</i>-communic acid (<b>10</b>) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen–DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (<b>7</b>) and of the synthetic intermediates <b>8</b> and <b>9</b> against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound <b>9</b> (IC₅₀ = 4.1 μM), which was twice as active as natural compound <b>7</b> (IC₅₀ = 8.3 μM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents