Cyclization of amino acid prepd. from 4,4-dimethylcyclohex-2-en-1-one by std. chem., yielded the dimeric and tetrameric macrolactams (I) and (II), resp., representing the first examples of "taxoid-like" compds. with heterocyclic B rings. I and II exhibited moderate antiproliferative activity in an in vitro cytotoxicity assay. Consequently, an orthogonally diprotected, dimeric macrolactam (III) (R = Me3CMe2Si) was synthesized and, after selective deprotection of the hydroxy group, was coupled with the docetaxel side chain to give the final compd. III [R = (S,R)-PhCH(NHCO2CMe3)CH(OH)CO] (IV), showing three-dimensional shape similarity to paclitaxel. Contrary to our expectations, IV proved to be as active as the parent compd. I. The structure of I has been confirmed by X-ray crystallog. anal. and is also reported.
Gentile, G., Fattori, D., Botta, M., Corelli, F., Fusar Bassini, D., Lamba, D. (2000). Synthesis of dimeric and tetrameric macrolactams with cytotoxic activity. CANADIAN JOURNAL OF CHEMISTRY, 78(6), 925-934 [10.1139/cjc-78-6-925].
Synthesis of dimeric and tetrameric macrolactams with cytotoxic activity
Botta, Maurizio;Corelli, Federico;
2000-01-01
Abstract
Cyclization of amino acid prepd. from 4,4-dimethylcyclohex-2-en-1-one by std. chem., yielded the dimeric and tetrameric macrolactams (I) and (II), resp., representing the first examples of "taxoid-like" compds. with heterocyclic B rings. I and II exhibited moderate antiproliferative activity in an in vitro cytotoxicity assay. Consequently, an orthogonally diprotected, dimeric macrolactam (III) (R = Me3CMe2Si) was synthesized and, after selective deprotection of the hydroxy group, was coupled with the docetaxel side chain to give the final compd. III [R = (S,R)-PhCH(NHCO2CMe3)CH(OH)CO] (IV), showing three-dimensional shape similarity to paclitaxel. Contrary to our expectations, IV proved to be as active as the parent compd. I. The structure of I has been confirmed by X-ray crystallog. anal. and is also reported.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/29819
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