Total Synthesis of Brevetoxin A:Part 1:First Generation Strategy and Construction of BCD Ring System

摘要

Discussed herein is our first generation strategy for the total synthesis of brevetoxin A. This approach relies upon dissection of the molecule at the nine-membered ring site (ring E). A Wittig coupling of requisite polycyclic fragments 3 and 4 followed by hydroxy dithioketal cyclization was expected to furnish the polycyclic framwork of brevetoxin A (1). Intermediate 8 was anticipated to be a valid synthetic precursor to phosphonium salt 3, and its synthesis was accomplished by a bis (lactonization)/ thionolactone formation/functionalization sequence. In order to test our synthetic strategy, the synthesis of an advanced model system (36) was attempted. Aldehyde 38 and phosphonium salt 37 were successfully synthesized and coupled through a Wittig reactrion. Unfortunately, the planned hydroxy dithiocketal cyclization to form the cructial nonacene (ring E)did not proceed as anticipated and this synthetic approach was discontinued.