Web Release Date: February 2,
Total Synthesis and Structural Elucidation of Azaspiracid-1. Final Assignment and Total Synthesis of the Correct Structure of Azaspiracid-1
Contribution from the Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, and Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093
Received August 15, 2005
Abstract:
The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C21-C27 fragment) reacting with a pentafluorophenol ester (C1-C20 fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C1-C27 fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C1-C20 epimer (2) and of several truncated analogues for biological investigations are described.
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