Direct Aminolysis of Ethoxycarbonylmethyl  1,4-Dihydropyridine-3-carboxylates

Vı̄gante, Brigita; Ruciņš, Mārtiņš; Plotniece, Aiva; Pajuste, Kārlis; Luntena, Iveta; Čekavičus, Brigita; Bisenieks, Egīls; Smits, Rufus; Дубурс, Г.; Sobolev, Arkadij

doi:10.3390/molecules201119697

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…TBD also efficiently catalyzes the aminolysis of esters under mild conditions, ,− an important transformation for the synthesis of pharmaceuticals, ,, whereas TMG, DBN, DBU, and MTBD were shown to be catalytically inactive here. ,, The potential of TBD in aminolysis reactions was impressively confirmed by the pilot-scale production of an H-PGDS inhibitor (Scheme ). …”

Section: Applications Of Tbdmentioning

confidence: 76%

Unique Superbase TBD (1,5,7-Triazabicyclo[4.4.0]dec-5-ene): From Catalytic Activity and One-Pot Synthesis to Broader Application in Industrial Chemistry

Fritz‐Langhals

2022

Org. Process Res. Dev.

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TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) is an organic superbase with unique catalytic effects due to its bifunctionality. It is already successfully used as a versatile catalyst, e.g., for transesterification, amidation, Michael addition, and aldol reactions, in technical silicone chemistry and even for enantioselective transformations. Currently, main applications are in innovative polymer chemistry (vitrimers, nonisocyanate polyurethanes, and polyureas). Restrictions of a broader application of TBD in technical processes due to its limited market availability and the complicated handling of its crystalline delivery form are now overcome by a simple one-pot synthesis of TBD, which generates an easy-to-make, ready-to-apply liquid formulation.

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Section: Applications Of Tbdmentioning

confidence: 76%

Unique Superbase TBD (1,5,7-Triazabicyclo[4.4.0]dec-5-ene): From Catalytic Activity and One-Pot Synthesis to Broader Application in Industrial Chemistry

Fritz‐Langhals

2022

Org. Process Res. Dev.

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“…To investigate a range of catalysts that have been described to facilitate the reaction between an activated ester and a primary amine, we screened the nucleophilic catalysts pyridine, 2-hydroxypyridine and NaCN, as well as the following transition metal ions: Ni(II), Cu(I), Cu(II), Zn(II), Fe(II), and Fe(III). − To study the effect of the selected catalysts, we followed the stability of LW+14 in DMSO containing 0.1% TEA as well as the reaction of LW+14 with a 50-fold molar excess of hexylamine. The presence of 0.5% pyridine or 2-hydroxypyridine in the reaction mixture had no effect on the chemical coupling yield and accelerated the undesirable intramolecular rearrangement (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…A number of chemical agents and biocatalysts are known to catalyze reactions between activated esters and primary amines including Lewis bases (e.g., pyridine, 2-hydroxypyridine), , Lewis acids (e.g., sodium cyanide and salts of zinc, nickel, iron, lanthanum, and zirconium), − and enzymes (e.g., Candida antarctica lipase B). − For example, La(III) trifluoromethanesulfonate was developed as catalyst for synthesizing a variety of amides directly from esters and amines under mild conditions . We therefore investigated a range of potential catalysts in view of their ability to reduce side reactions and to obtain efficient coupling with a reduced excess of the often costly labeling reagents.…”

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confidence: 99%

Specific Affinity Enrichment of Electrochemically Cleaved Peptides Based on Cu(II)-Mediated Spirolactone Tagging

et al. 2017

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Specific digestion of proteins is an essential step for mass spectrometry-based proteomics, and the chemical labeling of the resulting peptides is often used for peptide enrichment or the introduction of desirable tags. Electrochemical oxidation yielding specific cleavage C-terminal to tyrosine (Tyr) and tryptophan (Trp) residues provides a potential alternative to enzymatic digestion and a possibility for further chemical labeling by introducing reactive spirolactone moieties. However, spirolactone-containing peptides suffer from low stability due to hydrolysis and intramolecular side reactions. We found that Cu(II) ions stabilize the spirolactone and prevent intramolecular side reactions during chemical labeling, allowing efficient chemical tagging with a reduced excess of labeling reagent without intramolecular side reactions. On the basis of this reaction, we developed an analytical procedure combining electrochemical digestion, Cu(II)-mediated spirolactone biotinylation, and enrichment by avidin affinity chromatography with mass spectrometry. The method was optimized with the tripeptide LWL and subsequently applied to chicken egg white lysozyme, in which one biotinylated electrochemistry (EC)-cleaved peptide was identified after affinity enrichment. This proof-of-principle shows that specific enrichment of electrochemically cleaved spirolactone-containing peptides can be used for protein identification and notably that inclusion of Cu(II) ions is essential for stabilizing spirolactones for subsequent biotinylation.

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Toward Second‐Generation Cardiomyogenic and Anti‐cardiofibrotic 1,4‐Dihydropyridine‐Class TGFβ Inhibitors

et al. 2019

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Innovative therapeutic modalities for pharmacological intervention of transforming growth factor β (TGFβ)‐dependent diseases are of great value. b‐Annelated 1,4‐dihydropyridines (DHPs) might be such a class, as they induce TGFβ receptor type II degradation. However, intrinsic drawbacks are associated with this compound class and were systematically addressed in the presented study. It was possible to install polar functionalities and bioisosteric moieties at distinct sites of the molecules while maintaining TGFβ‐inhibitory activities. The introduction of a 2‐amino group or 7‐N‐alkyl modification proved to be successful strategies. Aqueous solubility was improved by up to seven‐fold at pH 7.4 and 200‐fold at pH 3 relative to the parent ethyl 4‐(biphenyl‐4‐yl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate. The therapeutic potential of the presented DHPs was further underscored in view of a potential dual mode of action: The differentiation of committed human iPSC‐derived cardiac progenitor cells (CPCs) was potently stimulated, and the rescue of cardiac fibrosis phenotypes was observed in engineered heart tissue (EHT) constructs.

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Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates

Cited by 7 publications

References 23 publications

Unique Superbase TBD (1,5,7-Triazabicyclo[4.4.0]dec-5-ene): From Catalytic Activity and One-Pot Synthesis to Broader Application in Industrial Chemistry

Unique Superbase TBD (1,5,7-Triazabicyclo[4.4.0]dec-5-ene): From Catalytic Activity and One-Pot Synthesis to Broader Application in Industrial Chemistry

Specific Affinity Enrichment of Electrochemically Cleaved Peptides Based on Cu(II)-Mediated Spirolactone Tagging

Toward Second‐Generation Cardiomyogenic and Anti‐cardiofibrotic 1,4‐Dihydropyridine‐Class TGFβ Inhibitors

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