Total Synthesis and Structural Elucidation of Azaspiracid-1. Construction of Key Building Blocks for Originally Proposed Structure

Syntheses of the three key building blocks (65, 98, and 100) required for the total synthesis of
the proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formation
for the construction of intermediate 98, and a Nozaki−Hiyama−Kishi coupling to assemble the required
carbon chain of fragment 100. The synthesized fragments, obtained stereoselectively in both their
enantiomeric forms, were expected to allow for the construction of all four stereoisomers proposed as
possible structures of azaspiracid-1 (1a−d), thus allowing the determination of both the relative and absolute
stereochemistry of the natural product.