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

摘要

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_1-C_(20)(7)and C_(21)-C_(27)(8)fragments,followed by a Stille-type coupling which allowed the incorporation of the C_(28)-C_(40)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.