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 C<SUB>1</SUB>-C<SUB>20</SUB> (7) and C<SUB>21</SUB>-C<SUB>27</SUB> (8) fragments, followed by a Stille-type coupling which allowed the incorporation of the C<SUB>28</SUB>-C<SUB>40</SUB> fragment (6) into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or <SUP>1</SUP>H NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin