13 research outputs found
Theoretical and NMR Conformational Studies of β-Proline Oligopeptides With Alternating Chirality of Pyrrolidine Units
(1SR,3RS,3aSR,6aRS)-Methyl 5-methyl-4,6-dioxo-3-[2-(trifluoromethyl)phenyl]octahydropyrrolo[3,4-c]pyrrole-1-carboxylate
In the title compound, C16H15F3N2O4, the relative stereochemistry of the four stereogenic C atoms has been determined. The carboxymethyl and 2-(trifluoromethyl)phenyl substituents of the pyrrolidine cycle have a cis mutual arrangement. The five-membered saturated azacycle adopts an envelope conformation with the N atom occupying the flap position. In the crystal, adjacent molecules are combined in centrosymmetric dimers by two weak N—H...O hydrogen bonds
Crystal structure of 4-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl] 2-methyl (2S,4S,5R)-1-[(2S,3R,5R)-5-methoxycarbonyl-2-(2-methylphenyl)pyrrolidine-3-carbonyl]-5-(2-methylphenyl)pyrrolidine-2,4-dicarboxylate
The title compound, C38H50N2O7, represents a chiral β-proline dipeptide. Corresponding stereogenic centres of constituting pyrrolidine units have opposite absolute configurations. The central amide fragment is planar within 0.1 Å and adopts a Z configuration along the N—CO bond. In the crystal, the hydrogen atoms of the methylene groups form several short intermolecular C—H...O contacts with the carbonyl oxygen atoms of an adjacent molecule. The only active amino hydrogen atom is not involved in hydrogen bonding
Theoretical and NMR Conformational Studies of β-Proline Oligopeptides With Alternating Chirality of Pyrrolidine Units
Pyrrolidine/Azepane Ring Expansion via Intramolecular Ullmann-Type Annulation/Rearrangement Cascade: Synthesis of Highly Functionalized 1<i>H</i>‑Benzazepines
5-Arylpyrrolidine-2-carboxylates with an ortho-halogen substituent at 5-aryl and an electron-withdrawing group
at the C4 position of the pyrrolidine ring were transformed
into 1H-benzoÂ[b]Âazepine-2-carboxylates
under CuÂ(I) promotion and microwave activation. Reaction promoter
copperÂ(I) thiophene-2-carboxylate has been generated in situ in the reaction’s environment from Cu2O and thiophene-2-carboxylic
acid. Functionalized 1H-benzoÂ[b]Âazepine-2-carboxylates
were obtained in racemic and optically active forms in 67–89%
yields. Subsequent stereoselective 1,3-dipolar cycloaddition and an
Ullmann-type annulation/rearrangement cascade (UARC) ensure a synthetic
route to oligomeric optically active benzazepine species with a well-defined
3D-structure
Pyrrolidine/Azepane Ring Expansion via Intramolecular Ullmann-Type Annulation/Rearrangement Cascade: Synthesis of Highly Functionalized 1<i>H</i>‑Benzazepines
5-Arylpyrrolidine-2-carboxylates with an ortho-halogen substituent at 5-aryl and an electron-withdrawing group
at the C4 position of the pyrrolidine ring were transformed
into 1H-benzoÂ[b]Âazepine-2-carboxylates
under CuÂ(I) promotion and microwave activation. Reaction promoter
copperÂ(I) thiophene-2-carboxylate has been generated in situ in the reaction’s environment from Cu2O and thiophene-2-carboxylic
acid. Functionalized 1H-benzoÂ[b]Âazepine-2-carboxylates
were obtained in racemic and optically active forms in 67–89%
yields. Subsequent stereoselective 1,3-dipolar cycloaddition and an
Ullmann-type annulation/rearrangement cascade (UARC) ensure a synthetic
route to oligomeric optically active benzazepine species with a well-defined
3D-structure
Theoretical and NMR Conformational Studies of β-Proline Oligopeptides With Alternating Chirality of Pyrrolidine Units
Synthetic β-peptides are potential functional mimetics of native α-proteins. A recently developed, novel, synthetic approach provides an effective route to the broad group of β-proline oligomers with alternating patterns of stereogenic centers. Conformation of the pyrrolidine ring, Z/E isomerism of β-peptide bonds, and hindered rotation of the neighboring monomers determine the spatial structure of this group of β-proline oligopeptides. Preferences in their structural organization and corresponding thermodynamic properties are determined by NMR spectroscopy, restrained molecular dynamics and quantum mechanics. The studied β-proline oligopeptides exist in dimethyl sulfoxide solution in a limited number of conformers, with compatible energy of formation and different spatial organization. In the β-proline tetrapeptide with alternating chirality of composing pyrrolidine units, one of three peptide bonds may exist in an E configuration. For the alternating β-proline pentapeptide, the presence of an E configuration for at least of one β-peptide bond is mandatory. In this case, three peptide bonds synchronously change their configurations. Larger polypeptides may only exist in the presence of several E configurations of β-peptide bonds forming a wave-like extended structure
Asymmetric synthesis and molecular docking study of enantiomerically pure pyrrolidine derivatives with potential antithrombin activity
The (2R,4R,5S)- and (2S,4S,5R)-enantiomers of 4-(tert-butyl) 2-methyl 5-(4-bromophenyl)-pyrrolidine-2,4-dicarboxylate 3 were synthesized efficiently with an ee of >90% on a gram scale using a FAM-catalytic methodology. Subsequent modification afforded enantiopure N-((4-chlorophenyl)thio)acetyl pyrrolidine derivatives 4, which are potential thrombin inhibitors according to comprehensive molecular docking studies
Presentation1.PDF
<p>Synthetic β-peptides are potential functional mimetics of native α-proteins. A recently developed, novel, synthetic approach provides an effective route to the broad group of β-proline oligomers with alternating patterns of stereogenic centers. Conformation of the pyrrolidine ring, Z/E isomerism of β-peptide bonds, and hindered rotation of the neighboring monomers determine the spatial structure of this group of β-proline oligopeptides. Preferences in their structural organization and corresponding thermodynamic properties are determined by NMR spectroscopy, restrained molecular dynamics and quantum mechanics. The studied β-proline oligopeptides exist in dimethyl sulfoxide solution in a limited number of conformers, with compatible energy of formation and different spatial organization. In the β-proline tetrapeptide with alternating chirality of composing pyrrolidine units, one of three peptide bonds may exist in an E configuration. For the alternating β-proline pentapeptide, the presence of an E configuration for at least of one β-peptide bond is mandatory. In this case, three peptide bonds synchronously change their configurations. Larger polypeptides may only exist in the presence of several E configurations of β-peptide bonds forming a wave-like extended structure.</p