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Total Synthesis of the Cyclic Depsipeptide Vioprolide D via its ( Z )‐Diastereoisomer
Author(s) -
Grab Hanusch A.,
Kirsch Volker C.,
Sieber Stephan A.,
Bach Thorsten
Publication year - 2020
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.202002328
Subject(s) - diastereomer , chemistry , depsipeptide , stereochemistry , thiazoline , yield (engineering) , total synthesis , cyclic peptide , ring (chemistry) , double bond , stereocenter , peptide , enantioselective synthesis , organic chemistry , catalysis , biochemistry , materials science , metallurgy
The first total synthesis of vioprolide D was accomplished in an overall yield of 2.0 % starting from methyl (2 S )‐3‐benzyloxy‐2‐hydroxypropanoate (16 steps in the longest linear sequence). The cyclic depsipeptide was assembled from two building blocks of similar size and complexity in a modular, highly convergent approach. Peptide bond formation at the C‐terminal dehydrobutyrine amino acid of the northern fragment was possible via its ( Z )‐diastereoisomer. After macrolactamization and formation of the thiazoline ring, the ( Z )‐double bond of the dehydrobutyrine unit was isomerized to the ( E )‐double bond of the natural product. The cytotoxicity of vioprolide D is significantly higher than that of its ( Z )‐diastereoisomer.