A Flexible Asymmetric Approach to Methyl 5-Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A
| Autor: | Pei-Qiang Huang, Jian-Liang Ye, Ai-E Wang, Yuan-Ping Ruan, Hong-Qiao Lan |
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| Rok vydání: | 2010 |
| Předmět: |
Biological Products
Natural product Molecular Structure Tetrapeptide Stereochemistry Organic Chemistry Molecular Conformation Enantioselective synthesis Absolute configuration Total synthesis Stereoisomerism General Chemistry Pyrrolidinones Catalysis chemistry.chemical_compound chemistry Yield (chemistry) Marine Toxins Optical rotation Oligopeptides Derivative (chemistry) |
| Zdroj: | Chemistry - A European Journal. 17:958-968 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201002063 |
| Popis: | By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the (13) C NMR spectrum, the (13) C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised. |
| Databáze: | OpenAIRE |
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