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Closed Access item Highly Stereoselective Total Synthesis of (+)-9-epi-Dictyostatin and (–)-12,13-bis-epi-Dictyostatin Eur. J

Authors:Zanato, Chiara
Pignataro, Luca
Ambrosi, Andrea
Hao, Zhongyan
Trigili, Chiara
Díaz, José Fernando
Barasoain, Isabel
Gennari, Cesare
Keywords:Medicinal chemistry, Natural products, Total synthesis, Asymmetric synthesis, Antitumor agents, Macrocycles
Issue Date:May-2011
Publisher:American Chemical Society
Citation:Journal of Organic Chemistry(14):2643-2661(2011)
Abstract:The total syntheses of (+)-9-epi-dictyostatin (1a) and (–)-12,13-bis-epi-dictyostatin (1b), diastereomers of the antimitotic marine sponge-derived macrolide (–)-dictyostatin (1), were achieved by creating 11 stereogenic centers and 4stereogenic double bonds with a high level of stereocontrol. The yield for the 29-step longest linear sequence from Roche ester was 1.53 and 1.52 %, respectively. The final key steps to these unnatural products were the addition of vinylzincates C10-C26 to aldehyde C1–C9 (leading surprisingly to complete stereoselectivity for the 9R-configuration in 28a and for the 9S-configuration in 12,13-bis-epimeric 28b), followed by Yamaguchi macrolactonization and global deprotection. (–)-12,13-Bis-epi-dictyostatin (1b) displayed a dramatic decrease of cytotoxicity and of the affinity toward the paclitaxel binding site of microtubules
Description:19 páginas, 9 esquemas, 2 tablas -- PAGS nros. 2643-2661
Publisher version (URL):http:dx.doi.org/10.1002/ejoc.201100244
URI:http://hdl.handle.net/10261/51678
ISSN:0022-3263
E-ISSNmetadata.dc.identifier.doi = DOI:1520-6904
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