Total synthesis of brevetoxin A: Part 3: Construction of GHIJ and BCDE ring systems

Successful syntheses of highly complex intermediates 2 (GHIJ ring system) a nd 3 (BCDE ring system) for the total synthesis of brevetoxin A (1) are des cribed. Several of our methodologies were utilized to achieve this goal: i) hydroxy epoxide cyclizations of intermediates 22 and 30 (rings I and H, re spectively); ii) hydroxy dithioketal cyclization of 45 (ring G); and, iii) palladium-catalyzed coupling with bis(cyclic ketene acetal phosphate) 68 (r ings B and D). With the knowledge gained from our previous model studies, 2 and 3 were expected to be pivotal intermediates on the synthetic route to brevetoxin A.