Iron(III) Catalyzed Direct Synthesis of <i>cis</i>-2,7-Disubstituted Oxepanes. The Shortest Total Synthesis of (+)-Isolaurepan

Prins cyclization of <i>bis</i>-homoallylic alcohols with aldehydes catalyzed by iron(III) salts shows excellent <i>cis</i> selectivity and yields to form 2,7-disubstituted oxepanes. The iron(III) is able to catalyze this process with unactivated olefins. This cyclization was used as the key step in the shortest total synthesis of (+)-isolaurepan

Comparative toxicological study of the novel protein phosphatase inhibitor 19-epi-okadaic acid in primary cultures of rat cerebellar cells

Okadaic acid (OKA) and analogues are frequent contaminants of coastal waters and seafood. Structure analysis of the isolated OKA analogue 19-epi-OKA showed important conformation differences expected to result in lower protein phosphatase (PP) inhibitory potencies than OKA. However, 19-epi-OKA and OKA inhibitory activities versus PP2A were unexpectedly found to be virtually equipotent. To investigate the toxicological relevance of these findings, we tested the effects of 19-epi-OKA on cultured cerebellar cells and compared them with those of OKA and its isomer dinophysistoxin-2. 19-epi-OKA caused degeneration of neurites and neuronal death with much lower potency than its congeners. The concentration of 19-epi-OKA that reduced after 24h the maximum neuronal survival (EC5024) by 50% was ~300nM compared with ~2nM and ~8nM for OKA and dinophysistoxin-2, respectively. Exposure to 19-epi-OKA resulted also in less toxicity for cultured glial cells (EC5024,19-epi-OKA ~ 600nM; EC5024,OKA ~ 20nM). 19-epi-OKA induced apoptotic condensation and fragmentation of chromatin, activation of caspases, and activation of ERK1/2 MAP kinases, features previously reported for OKA and dinophysistoxin-2. Also, differential sensitivity to 19-epi-OKA was observed between neuronal and glial cells, a specific characteristic shared by OKA and dinophysistoxin-2 but not by other toxins. Our results are consistent with 19-epi-OKA being included among the group of toxins of OKA and derivatives and support the suitability of cellular bioassays for the detection of these compounds.Peer reviewe

Glycoyessotoxin A, a New Yessotoxin Derivative from Cultures of Protoceratium reticulatum

The dinoflagellate Protoceratium reticulatum produces toxins of the yessotoxin group currently included in the diarrhetic shellfish poisoning class. In this paper we report on the isolation and structural elucidation of a 32-arabinoside of yessotoxin, G-YTXA (2), obtained from laboratory cultures of P. reticulatum (strain GG1AM) that possesses a pentose unit, β-arabinofuranose, as a side chain.Versión del edito