We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained Nα-amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Calculation of the conformational barriers for the cyclization reactions of various ring sizes demonstrated that the formation of amino acid-derived smaller rings by this reaction is thermodynamically unfavorable.
- MeSH
- Alkynes chemistry MeSH
- Amides chemical synthesis MeSH
- Amino Acids chemistry MeSH
- Amines chemistry MeSH
- Cyclization MeSH
- Diynes chemistry MeSH
- Catalysis MeSH
- Molecular Conformation MeSH
- Models, Molecular MeSH
- Solid-Phase Synthesis Techniques methods MeSH
- Thermodynamics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
An efficient and high-yielding solid phase synthesis of a small library of imidazolidin-2-ones and imidazol-2-ones was carried out employing a high chemo- and regioselective gold-catalyzed cycloisomerization as a key step. Polymer-supported amino acids derivatized with several alkyne functionalities combined with tosyl- and phenylureas have been subjected to gold-catalysis exhibiting exclusively C-N bond formation. The present work proves the potential of solid phase synthesis and homogeneous gold catalysis as an efficient and powerful synthetic tool for the generation of drug-like heterocycles.
- MeSH
- Alkynes chemistry MeSH
- Cyclization MeSH
- Imidazolidines chemical synthesis MeSH
- Catalysis MeSH
- Small Molecule Libraries chemical synthesis MeSH
- Molecular Structure MeSH
- Combinatorial Chemistry Techniques MeSH
- Solid-Phase Synthesis Techniques MeSH
- Gold chemistry MeSH
- Publication type
- Journal Article MeSH
A simple, versatile, protein-repulsive, substrate-independent biomimetic surface modification is presented that is based on the creation of a PEO brush on a polydopamine anchoring layer and its capacity for selective follow-up modifications with various ligands using a copper-catalyzed alkyne-azide cycloaddition reaction. The desired surface concentration of peptide biomimetic ligands can be controlled by adjusting the peptide concentration in the reaction mixture, then measuring the activity of (125)I-radiolabeled peptides that are immobilized on the substrates. The performance of the prepared substrates is tested in cell cultures with MEF cells and a human ECC line.
- MeSH
- Biomimetics * MeSH
- Cyclization MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Surface Properties MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
To identify novel estrogen receptor ligands a series of substituted 17alpha-arylestradiols were synthesized using the catalytic [2 + 2 + 2]cyclotrimerization of 17alpha-ethynylestradiol with various 1,7-diynes in the presence of Wilkinson's catalysts [Rh(PPh(3))(3)Cl]. The compounds were subjected to competitive binding assays, cell-based luciferase reporter assays, and proliferation assays. These experiments confirmed their estrogenic character and revealed some interesting properties like mixed partial/full agonism for ERalpha/ERbeta and different selectivity as a result of differing potencies for either ER.
- MeSH
- Transcriptional Activation MeSH
- Estrogen Receptor alpha agonists genetics MeSH
- Alkynes chemistry MeSH
- Estrogen Receptor beta agonists genetics MeSH
- Cell Line MeSH
- Cyclization MeSH
- Estradiol analogs & derivatives chemical synthesis pharmacology MeSH
- Fluorescence Polarization MeSH
- Binding, Competitive MeSH
- Humans MeSH
- Ligands MeSH
- Luciferases genetics MeSH
- Cell Line, Tumor MeSH
- Drug Partial Agonism MeSH
- Cell Proliferation drug effects MeSH
- Genes, Reporter MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
