Abstract
The first total synthesis of vioprolide D was accomplished in an overall yield of 2.0 % starting from methyl (2S)-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.
Original language | English |
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Pages (from-to) | 12357-12361 |
Number of pages | 5 |
Journal | Angewandte Chemie International Edition in English |
Volume | 59 |
Issue number | 30 |
DOIs | |
State | Published - 20 Jul 2020 |
Keywords
- antitumor agents
- isomerization
- macrocycles
- peptides
- total synthesis