ORGN 504 |
| Maikel Wijtmans, Johan Brinkhorst, Derek A. Pratt, and Ned A. Porter. Department of Chemistry, Vanderbilt University, 1822 Station B, Nashville, TN 37235 |
| Previously, we have shown that certain monocyclic and bicyclic 6-amino-3-pyridinols (1 – 3) show excellent chain-breaking antioxidant activity in solution (5, 28 and 88 times better than α-tocopherol, 5, respectively). In addition, lipophilic derivatives proved very effective in protecting human Low Density Lipoprotein towards oxidative damage. Inspired by this, a project was launched aimed at gaining efficient access to a wide variety of these compounds for more advanced studies. Early synthetic routes used a reliable but moderately yielding 3-bromopyridine-to-3-pyridinol conversion as the key step. Several attempts were pursued to optimize this conversion. Furthermore, substantially improved synthetic sequences to the bicyclic cores of 2 and 3 will be highlighted. Lastly, the synthesis of a racemic pyridinolic isostere of α-tocopherol, i.e. 4, was accomplished. This route included a novel, strongly solvent-dependent addition of n-alkyllithiums to α,α'-disubstituted-[1,8]-naphthyridines. |
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Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster
Division of Organic Chemistry |
