Second-generation total synthesis of azaspiracids-1, -2, and -3.
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.
Nicolaou
K C
KC
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@scripps.edu
Frederick
Michael O
MO
Loizidou
Eriketi Z
EZ
Petrovic
Goran
G
Cole
Kevin P
KP
Koftis
Theocharis V
TV
Yamada
Yoichi M A
YM
D001688:Biological Products / Q000737:chemistry; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D000095702:Polyether Toxins
D001688:Biological Products; D008387:Marine Toxins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins