Epi-, epoxy-, and C2-modified bengamides: synthesis and biological evaluation
| Autor: | Francisca Martín-Gálvez, Carlos Vivar-García, Francisco Sarabia, Antonio Sánchez-Ruiz, Cristina García-Ruiz |
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| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
Sulfonium Substituent Molecular Conformation Stereoisomerism Antineoplastic Agents HL-60 Cells chemistry.chemical_compound Polyketide Structure-Activity Relationship Aldol reaction Cell Line Tumor Human Umbilical Vein Endothelial Cells Structure–activity relationship Humans Oxazoles Biological evaluation Cell Proliferation Dose-Response Relationship Drug Organic Chemistry Epoxy HCT116 Cells chemistry visual_art visual_art.visual_art_medium MCF-7 Cells Drug Screening Assays Antitumor HT29 Cells |
| Zdroj: | The Journal of organic chemistry. 78(11) |
| ISSN: | 1520-6904 |
| Popis: | With the objective of investigating the influence of structural modifications of the polyketide chain of the bengamides upon their antitumoral activities, we targeted the preparation of bengamide E analogues with modification of the stereochemistry at C-2 and at C-3, the substituent at the C-2 position, and the presence of oxirane rings. For the synthesis of these analogues, a new synthetic method for asymmetric epoxidation, developed in our laboratories, was employed utilizing the chiral sulfonium salts 22 and 23. In order to access 2-epi-bengamide E from these epoxy amides, a synthetic methodology, developed by Miyashita, allowed an oxirane-ring-opening reaction with a double inversion of the configuration. Alternatively, an aldol reaction provided access to the same analogue in a shorter and more efficient manner. Finally, biological evaluation of all of these bengamide E analogues demonstrated that the polyketide chain is essential for the antitumor activity of these natural products, not being amenable to structural or configurational modifications. |
| Databáze: | OpenAIRE |
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