- Synthesis of 2,6-bridged piperazine-3-ones by N-acyliminium ion chemistry
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Several 2-substituted and 2,5-disubstituted piperazine-3,6-diones were synthesized starting from readily available α-amino acids. After activation of a lactam carbonyl via introduction of a methoxycarbonyl group onto nitrogen, this carbonyl was selectively reduced. Treatment of the resulting urethane with protic acid generated the corresponding N-acyliminium ion, which was trapped by a nucleophilic C2-side chain to provide 2,6-bridged piperazine-3-ones. Several aromatic, heteroaromatic, and nonaromatic side chains were used as π-nucleophiles. In addition, the effect of the presence of a C5-methyl group on the stereochemical outcome of the cyclization was examined.
- Veerman, Johan J. N.,Bon, Robin S.,Hue, Bui T. B.,Girones, Daniel,Rutjes, Floris P. J. T.,Van Maarseveen, Jan H.,Hiemstra, Henk
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- Predicting and improving the membrane permeability of peptidic small molecules
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We evaluate experimentally and computationally the membrane permeability of matched sets of peptidic small molecules bearing natural or bioisosteric unnatural amino acids. We find that the intentional introduction of hydrogen bond acceptor-donor pairs in
- Rafi, Salma B.,Hearn, Brian R.,Vedantham, Punitha,Jacobson, Matthew P.,Renslo, Adam R.
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experimental part
p. 3163 - 3169
(2012/06/18)
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