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(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 (1)H NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin.
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
K C
KC
Nicolaou
David Y-K
DY
Chen
Yiwei
Y
Li
Noriaki
N
Uesaka
Goran
G
Petrovic
Theocharis V
TV
Koftis
Federico
F
Bernal
Michael O
MO
Frederick
Mugesh
M
Govindasamy
Taotao
T
Ling
Petri M
PM
Pihko
Wenjun
W
Tang
Stepan
S
Vyskocil
D018360:Crystallography, X-Ray; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D000095702:Polyether Toxins
D008387:Marine Toxins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins