Brevetoxin, cyclization reactions

In the synthetic studies of the marine natural products brevetoxins A and B, Nicolaou and coworkers [157] developed a highly efficient cyclization reaction of hydroxy dithioketals leading to oxocenes. As shown in Scheme 88, exposure of the hydroxy dithioketal 261 to 1.1 equiv of AT-chlorosuccinimide (NCS) in CH3CN in the presence of 2 equiv of 2,6-lutidine, 1.1 equiv of AgNOj, molecular sieves and silica gel at 25 °C for 5 min led to the oxocene 262 in 95% yield. 

Recent advances in the synthesis of trans-iused polycyclic ethers by hydroxy epoxide cyclization reactions via monocyclic epoxonium ion intermediates and ether ring expansion reactions via bicyclic epoxonium ion intermediates are described in a review by Fujiwara and Murai. Natural trans-iu eA polycyclic ethers (e.g., brevetoxin A and ciguatoxin), produced by marine sources such as dinoflagellates, are hypothesized to be constructed from the corresponding polyepoxide precursors by a cascade of ring-closure reactions, which has prompted much work in the development of new methods for the construction of cyclic ethers from epoxides <2004BCJ2129>. 

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