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Synthesis and Biological Evaluation of (−)-16-Normethyldictyostatin:  A Potent Analogue of (−)-Dictyostatin

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journal contribution
posted on 07.07.2005, 00:00 by Youseung Shin, Jean-Hugues Fournier, Raghavan Balachandran, Charitha Madiraju, Brianne S. Raccor, Guangyu Zhu, Michael C. Edler, Ernest Hamel, Billy W. Day, Dennis P. Curran
(−)-16-Normethyldictyostatin has been made by total synthesis and is a potent antitumor agent in cells expressing wild-type tubulin and in one mutant cell line that is resistant to paclitaxel, but it is much less active than dictyostatin in another paclitaxel-resistant cell line where Val is substituted for Phe270. This provides strong evidence that the C16 methyl group of the dictyostatins is oriented toward Phe270 in the paclitaxel-binding site on β-tubulin.