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Total Synthesis of the Antimitotic Marine Macrolide (−)‐Leiodermatolide
Author(s) -
Paterson Ian,
Ng Kenneth K.H.,
Williams Simon,
Millican David C.,
Dalby Stephen M.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201310164
Subject(s) - antimitotic agent , total synthesis , aldol reaction , stereochemistry , tubulin , chemistry , enantiomer , yield (engineering) , combinatorial chemistry , biology , computational biology , biochemistry , microtubule , microbiology and biotechnology , materials science , metallurgy , catalysis
Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin‐targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2 % yield) based on a convergent sequence of palladium‐mediated fragment assembly and macrolactonization. Boron‐mediated aldol reactions were used to configure the three key fragments 2 , 5 , and 6 by employing the appropriate enantiomer of the lactate‐derived ketone 7 .