Total synthesis and structural elucidation of azaspiracid-1. Construction of key building blocks for originally proposed structure.
Syntheses of the three key building blocks (65, 98, and 100) required for the total synthesis of the proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formation for the construction of intermediate 98, and a Nozaki-Hiyama-Kishi coupling to assemble the required carbon chain of fragment 100. The synthesized fragments, obtained stereoselectively in both their enantiomeric forms, were expected to allow for the construction of all four stereoisomers proposed as possible structures of azaspiracid-1 (1a-d), thus allowing the determination of both the relative and absolute stereochemistry of the natural product.
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
Pihko
Petri M
PM
Bernal
Federico
F
Frederick
Michael O
MO
Qian
Wenyuan
W
Uesaka
Noriaki
N
Diedrichs
Nicole
N
Hinrichs
Jürgen
J
Koftis
Theocharis V
TV
Loizidou
Eriketi
E
Petrovic
Goran
G
Rodriquez
Manuela
M
Sarlah
David
D
Zou
Ning
N
D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013454:Sulfoxides / Q000737:chemistry; D000095702:Polyether Toxins
D008387:Marine Toxins; D013141:Spiro Compounds; D013454:Sulfoxides; C406592:azaspiracid; D000095702:Polyether Toxins