Imidazo[1,2-<i>a</i>]pyrazine-3,6-diones Derived from α-Amino Acids:  A Theoretical Mechanistic Study of Their Formation via Pyrolysis and Silica-Catalyzed Process

Contreras‐Torres, Flavio F.; Basiuk, Vladimir A.

doi:10.1021/jp061331m

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…O-N Intramolecular acyl migration has found a wide use in organic chemistry [122][123][124][125][126]. Thus, this rearrangement has been applied in the synthesis of peptidomimetics: including -secretase inhibitors [127,128], prolyl endopeptidase inhibitor eurystatin A [129], HIV-protease inhibitors [130], and many others [131][132][133][134][135][136][137].…”

Section: Other Application Of O-n Intramolecular Acyl Migration Reactionmentioning

confidence: 99%

Application of the O-N Intramolecular Acyl Migration Reaction in Medicinal Chemistry

Skwarczynski¹,

Kiso

2007

CMC

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The O-N intramolecular acyl migration, also named as an acyl shift or acyl transfer reaction, is well-known in organic and peptide chemistry as a simple rearrangement which proceeds under very mild aqueous conditions. Despite a long history with this reaction, its application in medicinal chemistry has only lately been proposed. In the last decade, this reaction has been intensively studied and several applications of this rearrangement in medicinal chemistry have appeared. O-N Intramolecular acyl migration has been employed in "no auxiliary, no byproduct" prodrug strategies (prodrugs of paclitaxel and other taxoids, prodrugs of HIV protease inhibitors), for the synthesis of peptides containing difficult sequences via "O-acyl isopeptide method", including Alzheimer's disease related amyloid beta peptide (Abeta) 1-42, and in the design of pH-, photo- or enzyme-triggered click peptides, as a potential powerful tool for identifying the pathological functions of amyloid beta peptides in Alzheimer's disease. This review summarized recent advances in the application of O-N intramolecular acyl migration with special focus on medicinal chemistry.

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Section: Other Application Of O-n Intramolecular Acyl Migration Reactionmentioning

confidence: 99%

Application of the O-N Intramolecular Acyl Migration Reaction in Medicinal Chemistry

Skwarczynski¹,

Kiso

2007

CMC

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“…The latter fact can be directly associated with the selective detection, thermochemical stability, or simply because cycle-condensation reactions of amino acids are not able to produce enough amounts of imidazo[1,2- a ]pyrazines. Previous quantum chemical calculations suggested that the formation of imidazo[1,2- a ]pyrazines can proceed overcoming a high reaction barrier of about 49 kcal mol –1 and only supported by a silica-catalyzed process. This has opened up an area of great dubiety about the formation and the spectroscopic properties − of imidazo[1,2- a ]pyrazines, which deserves more definitive answers and novel approaches for experimental identification.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, time-dependent DFT (TD-DFT) calculations were carried out to access the orbital contributions to each of the transitions observed in the absorption spectrum, and molecular excitation energies were obtained for both isolated molecule and metallic cluster-organic compounds. Arising from sublimation of α-amino-acids (e.g., glycine), bi and tricyclic imidazo[1,2- a ]pyrazines prepared require the formation of a first intermediate . The current series of molecules studied correspond to glycine (Gly, 1 ), piperazine-2,5-dione (DKP, 2 ), hexahydroimidazo[1,2- a ]pyrazine-3,6-dione (BCA, 3 ), and hexahydroimidazo[1,2- a ]imidazo[1,2- d ]pyrazine-3,8-dione (TCA, 4 ), which all are depicted in Scheme .…”

Section: Introductionmentioning

confidence: 99%

Dispersion-Corrected Density Functional Theory Study of the Noncovalent Complexes Formed with Imidazo[1,2-a]pyrazines Adsorbed onto Silver Clusters

Contreras‐Torres

2019

ACS Omega

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Imidazo[1,2-a]pyrazines are cyclic amidine-type compounds composed of α-amino acid residues. A full structural identification of these molecules constitutes an analytical challenge, especially when imidazo[1,2-a]pyrazines are obtained from physical processes (e.g., sublimation and pyrolysis of amino acids). A valuable source of molecular information can be obtained from absorption spectroscopies and related techniques encompassing the use of metallic substrates. The aim of this study is to provide new knowledge and insights into the noncovalent intermolecular interactions between imidazo[1,2-a]pyrazines and two Ag n (n = 4 and 20) clusters using density functional theory (DFT) methods. Semiempirical DFT dispersion (DFT-D) corrections were addressed using Grimme’s dispersion (GD2) and Austin–Petersson–Frisch (APF) functionals in conjunction with the 6-31+G(d,p) + LANL2DZ mixed basis set. These DFT-D methods describe strong interactions; besides, in all cases, the APF dispersion (APF-D) energies of interaction appear to be consistently overestimated. In comparison with B3LYP calculations, the mean values for the difference in the energies of interaction calculated are 2.25 (GD2) and 6.24 (APF-D) kcal mol–1 for Ag4–molecules, and 2.30 (GD2) and 8.53 (APF-D) kcal mol–1 for Ag20–molecules. The effect of applying GD2 and APF-D corrections to the noncovalent complexes is nuanced in the intermolecular distances calculated, mainly in the Ag···N(amidine) bonding, which appears to play the most important role for the adsorptive process. Selective enhancement and considerable red shifts for Raman vibrations suggest strong interactions, whereas a charge redistribution involving the metallic substrate and the absorbate leads to a significant rearrangement of frontier molecular orbitals mainly in the Ag20–molecule complexes. Finally, time-dependent DFT calculations were carried out to access the orbital contributions to each of the transitions observed in the absorption spectrum. The corresponding UV–vis spectra involve transitions in the visible region at around 400 and 550 nm for the Ag4–molecule and the Ag20–molecule complexes, respectively.

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“…This reaction probably proceeds through the corresponding cyclic dipeptides. [14,17] In the course of our studies on a-amino acids in different binding states, [15,[18][19][20] we have noticedt hat information about the solid thermolysis products that form from neat bulk glycine is scarce. This is surprising not only because glycinei st he simplest amino acid but also because it is considered highly relevant in prebiotic chemistry studies.…”

Section: Introductionmentioning

confidence: 99%

Hypercondensation of an Amino Acid: Synthesis and Characterization of a Black Glycine Polymer

Fox

Dalai

Lambert

et al. 2015

Chemistry A European J

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A granular material was obtained by thermal polymerization of glycine at 200 °C. It has been named "thermomelanoid" because of its strikingly deep-black color. The polymerization process is mainly a dehydration condensation leading to conventional amide bonds, and also CC double bonds that are formed from CO and CH2 groups ("hypercondensation"). Spectroscopic data, in particular from (13) C and (15) N solid-state cross-polarization magic angle spinning (CP-MAS) NMR spectra, suggest that the black color is due to (cross-)conjugated CC, CO, and NH groups. Small glycine peptides, especially triglycine, appear to be key intermediates in the formation of the thermomelanoid. This has been concluded by comparing the thermal behavior of glyn homopeptides (n=2-6) and glycine. The glycine polymerization was accompanied by the formation of small amounts of byproducts. Notably, a few percent of alanine and aspartic acid could be detected in the polymer. By using (13) C-labeled glycine, it was shown that these two amino acids formed through a common pathway, namely CαCα bond formation between glycine molecules. The thermomelanoid is hydrolyzed by strong acids and bases at room temperature, forming brown solutions.

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Imidazo[1,2-a]pyrazine-3,6-diones Derived from α-Amino Acids: A Theoretical Mechanistic Study of Their Formation via Pyrolysis and Silica-Catalyzed Process

Cited by 9 publications

References 54 publications

Application of the O-N Intramolecular Acyl Migration Reaction in Medicinal Chemistry

Application of the O-N Intramolecular Acyl Migration Reaction in Medicinal Chemistry

Dispersion-Corrected Density Functional Theory Study of the Noncovalent Complexes Formed with Imidazo[1,2-a]pyrazines Adsorbed onto Silver Clusters

Hypercondensation of an Amino Acid: Synthesis and Characterization of a Black Glycine Polymer

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