Total Synthesis and Structural Elucidation of Azaspiracid-1. Synthesis-Based Analysis of Originally Proposed Structures and Indication of Their Non-Identity to the Natural Product

The key building blocks (6, 7, and 8) for the intended construction of the originally proposed
structures of azaspiracid-1, a potent marine-derived neurotoxin, were coupled and the products elaborated
to the targeted compounds (1a,b) and their C-20 epimers (2 and 3). The assembly of the three intermediates
was accomplished by a dithiane-based coupling reaction that united the C1−C20 (7) and C21−C27 (8)
fragments, followed by a Stille-type coupling which allowed the incorporation of the C28−C40 fragment (6)
into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or
1H NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this
notorious biotoxin.