Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D
Lagunamide D is a structurally distinct 26-membered cytotoxic cyclic depsipeptide, originally isolated from a marine cyanobacterium. It exhibits potent antiproliferative activity in the low nanomolar range against A549 human lung adenocarcinoma cells and HCT116 colon cancer cells. A significant chal...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/3/99 |
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| Summary: | Lagunamide D is a structurally distinct 26-membered cytotoxic cyclic depsipeptide, originally isolated from a marine cyanobacterium. It exhibits potent antiproliferative activity in the low nanomolar range against A549 human lung adenocarcinoma cells and HCT116 colon cancer cells. A significant challenge associated with lagunamide D is its propensity for intramolecular acyl migration, which leads to the formation of a contracted 24-membered analog, lagunamide D′. This structural rearrangement complicates its isolation, characterization, and synthesis. In this study, the total synthesis of lagunamide D was achieved in a 14-step longest linear sequence, starting from the known intermediate <b>17</b>, with an overall yield of 4.6%. The synthetic strategy involved several key transformations, including Ghosh’s TiCl<sub>4</sub>-promoted anti-aldol reaction, Corey–Bakshi–Shibata reduction (CBS reduction), cross-metathesis, Pinnick oxidation, and Yamaguchi esterification. Furthermore, this synthetic effort unambiguously confirmed the stereochemistry of the natural product. |
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| ISSN: | 1660-3397 |