TY - JOUR
T1 - Total synthesis of (+)-amphidinolide A. Assembly of the fragments
AU - Trost, Barry M.
AU - Wrobleski, Stephen T.
AU - Chisholm, John D.
AU - Harrington, Paul E.
AU - Jung, Michael
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/10/5
Y1 - 2005/10/5
N2 - The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.
AB - The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.
UR - http://www.scopus.com/inward/record.url?scp=25844435856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25844435856&partnerID=8YFLogxK
U2 - 10.1021/ja0533646
DO - 10.1021/ja0533646
M3 - Article
C2 - 16190724
AN - SCOPUS:25844435856
SN - 0002-7863
VL - 127
SP - 13589
EP - 13597
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 39
ER -