TY - JOUR
T1 - Total synthesis and structural elucidation of azaspiracid-1. Construction of key building blocks for originally proposed structure
AU - Nicolaou, K. C.
AU - Pihko, Petri M.
AU - Bernal, Federico
AU - Frederick, Michael O.
AU - Qian, Wenyuan
AU - Uesaka, Noriaki
AU - Diedrichs, Nicole
AU - Hinrichs, Jürgen
AU - Koftis, Theocharis V.
AU - Loizidou, Eriketi
AU - Petrovic, Goran
AU - Rodriquez, Manuela
AU - Sarlah, David
AU - Zou, Ning
PY - 2006/2/22
Y1 - 2006/2/22
N2 - 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.
AB - 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.
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U2 - 10.1021/ja0547477
DO - 10.1021/ja0547477
M3 - Article
C2 - 16478178
AN - SCOPUS:33644520879
VL - 128
SP - 2244
EP - 2257
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 7
ER -