116650-33-0Relevant articles and documents
Microenvironmental effects on the solvent quenching rate in constrained tryptophan derivatives
Yu, Hong-Tao,Vela, Marco A.,Fronczek, Frank R.,McLaughlin, Mark L.,Barkley, Mary D.
, p. 348 - 357 (1995)
Solvent quenching is one of several environmentally sensitive nonradiative decay pathways available to the indole chromophore. It is characterized by 2-3-fold deuterium isotope effects and strong temperature dependence with frequency factors of 1015-1017 s-1 and activation energies of 11-13 kcal/mol in aqueous solution. The effects of ionization state, proximity of the amino group to the indole ring, and N-methylation of indole nitrogen on the solvent quenching rate were examined in four constrained tryptophan derivatives: 1,2,3,4-tetrahydro-2-carboline, 3-amino-1,2,3,4-tetrahydrocarbazole, 3-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, and 9-methyl-1,2,3,4-tetrahydro-2-carboline-3-carboxylic acid. The constrained derivatives had at most two ground-state conformations, as determined by X-ray crystallography, molecular mechanics calculations, and 1H NMR. Fluorescence lifetimes were assigned to ground-state conformations based on relative populations of conformers and amplitudes of fluorescence decays. Solvent quenching rates were determined from the temperature dependence of the fluorescence lifetime. The solvent quenching rate is decreased by protonation of the amino group in all compounds. It is slower in the carboline derivatives, where the amino group is two bonds away from the indole ring, than in the tetrahydrocarbazole derivatives, where the amino group is three bonds away. In the tetrahydrocarbazoles, the solvent quenching rate is slower in the conformer with the ammonium in the pseudoaxial position closer to the indole ring than in the conformer with the ammonium in the pseudoequatorial position pointing away from the ring. These results suggest that the water quenching rate of tryptophans on protein or peptide surfaces is modulated by proximal ammonium groups.
Fluorescence Studies with Tryptophan Analogues: Excited State Interactions Involving the Side Chain Amino Group
Eftink, Maurice R.,Jia, Yiwei,Hu, Dana,Ghiron, Camillo, A.
, p. 5713 - 5723 (1995)
The fluorescence of a large set of tryptophan analogues, including several that are conformationally constrained, was studied.The constrained analogues include tetrahydrocarboline-3-carboxylic acid and 3-amino-3-carboxytetrahydrocarbazole.Steady state and time-resolved fluorescence measurements were made as a function of pH.The fluorescence quantum yields of the constrained analogues are higher than those for the unconstrained counterparts.The emission intensity of the constrained analogues, as well as 4-methyltryptophan, decreases with deprotonation of the side chain α-ammonium groups; this is in contrast to the increase in fluorescence of tryptophan with deprotonation of this group.These results are consistent with the existence of excited state proton transfer to carbon 4 of the indole ring as a quenching mechanism, which is sterically prohibited in the constrained analogues and 4-methyltryptophan.From quantum yield and lifetime data (most decays are nonexponential), the effective rate constant for nonradiative depopulation of the excited state was calculated.For tryptophan analogues having two side chain functional groups, there is a synergistic effect; the presence of two side chain groups causes more quenching than expected from the sum of the individual contributions.For analogues having an α-ammonium group, this synergism appears to be correlated with an induced change in the pKa of this group.Deprotonation of this α-ammonium group also caused a red shift in the emission of these compounds; this appears to be due to electrostatic repulsion between the α-NH3+ group and the excited indole dipole.
INDOLE AHR INHIBITORS AND USES THEREOF
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, (2018/11/22)
The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
Asymmetric chemoenzymatic synthesis of ramatroban using lipases and oxidoreductases
Busto, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
, p. 4842 - 4848 (2012/07/31)
A chemoenzymatic asymmetric route for the preparation of enantiopure (R)-ramatroban has been developed for the first time. The action of lipases and oxidoreductases has been independently studied, and both were found as excellent biocatalysts for the production of adequate chiral intermediates under very mild reaction conditions. CAL-B efficiently catalyzed the resolution of (±)-2,3,4,9-tetrahydro-1H-carbazol-3-ol that was acylated with high stereocontrol. On the other hand, ADH-A mediated bioreduction of 4,9-dihydro-1H-carbazol-3(2H)-one provided an alternative access to the same enantiopure alcohol previously obtained through lipase-catalyzed resolution, a useful synthetic building block in the synthesis of ramatroban. Inversion of the absolute configuration of (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol has been identified as a key point in the synthetic route, optimizing this process to avoid racemization of the azide intermediate, finally yielding (R)-ramatroban in enantiopure form by the formation of the corresponding amine and the convenient functionalization of both exocyclic and indole nitrogen atoms.
