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Second‐Generation Total Synthesis of Azaspiracids‐1, ‐2, and ‐3
Author(s) -
Nicolaou K. C.,
Frederick Michael O.,
Loizidou Eriketi Z.,
Petrovic Goran,
Cole Kevin P.,
Koftis Theocharis V.,
Yamada Yoichi M. A.
Publication year - 2006
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200600059
Subject(s) - stille reaction , chemistry , stereochemistry , ring (chemistry) , combinatorial chemistry , trifluoromethanesulfonate , organic chemistry , catalysis
The naturally occurring but scarce marine neurotoxins azaspiracids‐1, ‐2, and ‐3 have been synthesized from five key building blocks by a convergent strategy that involved dithiane and Stille coupling reactions. The ABCD fragments were constructed through a cascade reaction involving deprotection/self‐assembly of the precursors, while the FGHI fragment was forged by a neodymium triflate‐induced cyclization. The final ring closure (ring G) was achieved, after the union of all fragments, through an iodoetherification reaction followed by reductive removal of the facilitating iodine residue. These improved, second‐generation routes confirm the absolute structures and render all three azaspiracids readily available for biological studies.