Synthesis of dimeric and tetrameric macrolactams with cytotoxic activity1
| Autor: | Gabriella Gentile, Daniela Fattori, Maurizio Botta, Federico Corelli, Domenico Fusar-Bassini, Doriano Lamba |
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| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Canadian Journal of Chemistry. 78:925-934 |
| ISSN: | 1480-3291 0008-4042 |
| DOI: | 10.1139/v00-080 |
| Popis: | Cyclization of amino acid 14, in turn prepared from 4,4-dimethylcyclohex-2-en-1-one by standard chemistry, yielded the dimeric and tetrameric macrolactams 15 and 16, respectively, representing the first examples of "taxoid-like" compounds with heterocyclic B rings. Compounds 15 and 16 exhibited moderate antiproliferative activity in an in vitro cytotoxicity assay. Consequently, an orthogonally diprotected, dimeric macrolactam 19 was synthesized and, after selective deprotection of the hydroxy group, was coupled with the docetaxel side chain to give the final compound 2, showing three-dimensional shape similarity to paclitaxel. Contrary to our expectations, 2 proved to be as active as the parent compound 15. The structure of 15 has been confirmed by X-ray crystallographic analysis and is also reported.Key words: macrolactams, macrocyclic compounds, taxane analogs, cytotoxic activity. |
| Databáze: | OpenAIRE |
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