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Highly Stereoselective Total Synthesis of (+)‐9‐ epi ‐Dictyostatin and (–)‐12,13‐Bis‐ epi ‐dictyostatin
Author(s) -
Zanato Chiara,
Pignataro Luca,
Ambrosi Andrea,
Hao Zhongyan,
Trigili Chiara,
Díaz José Fernando,
Barasoain Isabel,
Gennari Cesare
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100244
Subject(s) - stereocenter , chemistry , stereoselectivity , total synthesis , stereochemistry , aldehyde , diastereomer , yield (engineering) , enantioselective synthesis , organic chemistry , catalysis , materials science , metallurgy
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 9 R ‐configuration in 28a and for the 9 S ‐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.