ORGN 370 |
| Here we describe the synthesis of a new classes of α-helix mimetics having two substituted piperazine rings in 1, 4 positions of a benzene ring and hydrophobic amino acid side chains, with defined configuration. The substituents mimic groups in i, i+4 and i+7 positions of a peptidic α-helix. Inspired by Hamilton and coworker's terphenyl scaffolds, we sought improved synthetic accessibility, improved solubility in water and introduced chirality to the hydrophobic side-chains of key positions. We used piperazine derivatives because they have desired pharmacological properties. The synthesis of 1, 4-dipiperazino benzene began with 2-bromo-5-iodotoluene and (S)-1-benzyl-3/2-alkylpiperazine. For the first C-N coupling we used Cu(I)/rac-BINOL as catalytic system at room temperature and for the second Pd(0)/ rac-BINAP as catalytic system at 120-128ºC. The spectroscopic data suggested that 1, 4-dipiperazino benzene mimic an α-helix structure. This allows a more facile preparation of α helix mimics.
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Heterocycles and Aromatics, Molecular Recognition and Self Assembly
8:00 PM-10:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Hall A, Poster
Division of Organic Chemistry |
