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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| Format: | Article |
| Language: | English |
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MDPI AG
2025-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/3/99 |
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| author | Huiru Nan Xiong-En Long Jianfei He Hailiang Xing Min-Jing Cheng Jin-Bao Peng Tao Ye Jia-Lei Yan Junyang Liu |
| author_facet | Huiru Nan Xiong-En Long Jianfei He Hailiang Xing Min-Jing Cheng Jin-Bao Peng Tao Ye Jia-Lei Yan Junyang Liu |
| author_sort | Huiru Nan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5cc5be767f5f4237a4a8b3fb3b15e279 |
| institution | OA Journals |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-5cc5be767f5f4237a4a8b3fb3b15e2792025-08-20T02:11:11ZengMDPI AGMarine Drugs1660-33972025-02-012339910.3390/md23030099Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide DHuiru Nan0Xiong-En Long1Jianfei He2Hailiang Xing3Min-Jing Cheng4Jin-Bao Peng5Tao Ye6Jia-Lei Yan7Junyang Liu8School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaCenter for Bioactive Natural Molecules and Innovative Drugs, and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, ChinaLagunamide 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.https://www.mdpi.com/1660-3397/23/3/99lagunamide Dmarine natural productsdepsipeptidetotal synthesis |
| spellingShingle | Huiru Nan Xiong-En Long Jianfei He Hailiang Xing Min-Jing Cheng Jin-Bao Peng Tao Ye Jia-Lei Yan Junyang Liu Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D Marine Drugs lagunamide D marine natural products depsipeptide total synthesis |
| title | Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D |
| title_full | Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D |
| title_fullStr | Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D |
| title_full_unstemmed | Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D |
| title_short | Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D |
| title_sort | total synthesis of the marine cyclic depsipeptide lagunamide d |
| topic | lagunamide D marine natural products depsipeptide total synthesis |
| url | https://www.mdpi.com/1660-3397/23/3/99 |
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