A Highly Convergent Approach to Brevetoxin A.

Through optimized, scaled-up routes to the G and J rings of brevetoxin A, a convergent strategy based upon a Horner-Wadsworth-Emmons coupling reaction completed the GHIJ fragment. Further studies toward an alternative protecting group strategy for the GHIJ fragment elucidated a shortened synthesis. The union of a GHIJ fragment aldehyde with a BCDE fragment phosphine oxide was accomplished using a Horner-Wittig reaction, and the resulting compound was taken on to the decacyclic core through a dithioketal cyclization/reductive etherification sequence. The advanced intermediate thus obtained is expected to be a viable precursor to brevetoxin A.