Total synthesis of the cyclodepsipeptide apratoxin A and its analogues and assessment of their biological activities
Abstract
A novel total synthesis of apratoxin A is described, with key steps including the assembly of its ketide segment through a D ‐proline‐catalyzed direct aldol reaction and Oppolzer's anti aldol reaction and the preparation of its thiazoline unit in a biomimetic synthesis. An oxazoline analogue of apratoxin A has also been elaborated by a similar approach. This compound has a potency against HeLa cell proliferation only slightly lower than that of apratoxin A, whilst a C(40)‐demethylated oxazoline analogue of apratoxin A displays a much lower cytotoxicity and the C(37)‐epimer and C(37) demethylation product of this new analogue are inactive. These results suggest that the two methyl groups at C(37) and C(40) and the stereochemistry at C(37) are essential for the potent cellular activity of the oxazoline analogue of apratoxin A. Further biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase.
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Apratoxin A exerts cytotoxic effects against human HeLa cervical carcinoma cells via cell cycle inhibition.
“Apratoxin A, a cyclic depsipeptide, exerted cytotoxic effects against human HeLa cervical carcinoma cells via cell cycle inhibition [181].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [181]
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- Authors
- Ma, D., Zou, B., Cai, G., Hu, X., & Liu, J. O.
- Affiliations
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Johns Hopkins University (US)
- Venue
- Chemistry – A European Journal
- Publisher
- Wiley
- Published
- 2006-09-28
- Volume
- 12
- Issue
- 29
- Pages
- 7615-7626
- ISSN
- 0947-6539 (ISSN-L)
- 1521-3765
- OpenAlex
- W2029681548
- Cited by
- 99
- References
- 46
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 6
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemistry - A European Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Synthetic Organic Chemistry
- Physical Sciences › Chemistry › Organic Chemistry › Organic Chemistry Synthesis Methods
- Keywords
- total synthesis, cyclodepsipeptides, biomimetic synthesis, cytotoxicity, G1 cell cycle arrest, structure-activity relationship
- MeSH terms
- Antineoplastic Agents, Bacterial Toxins, Cell Cycle, HeLa Cells, Humans, Methylation, Oxazoles, Peptides, Cyclic, Stereoisomerism, Structure-Activity Relationship, G1 Phase, Depsipeptides, Cell Proliferation
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