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Chemical Reviews Oct 2021In this contribution, we provide a comprehensive overview of acyclic twisted amides, covering the literature since 1993 (the year of the first recognized report on... (Review)
Review
In this contribution, we provide a comprehensive overview of acyclic twisted amides, covering the literature since 1993 (the year of the first recognized report on acyclic twisted amides) through June 2020. The review focuses on classes of acyclic twisted amides and their key structural properties, such as amide bond twist and nitrogen pyramidalization, which are primarily responsible for disrupting to π* conjugation. Through discussing acyclic twisted amides in comparison with the classic bridged lactams and conformationally restricted cyclic fused amides, the reader is provided with an overview of amidic distortion that results in novel conformational features of acyclic amides that can be exploited in various fields of chemistry ranging from organic synthesis and polymers to biochemistry and structural chemistry and the current position of acyclic twisted amides in modern chemistry.
Topics: Amides; Chemistry Techniques, Synthetic; Lactams; Molecular Conformation; Nitrogen
PubMed: 34406005
DOI: 10.1021/acs.chemrev.1c00225 -
Journal of the American Chemical Society Feb 2016DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been...
DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases.
Topics: Amides; Catalysis; DNA; Hydrolysis
PubMed: 26854515
DOI: 10.1021/jacs.5b12647 -
Angewandte Chemie (International Ed. in... Jul 2021Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme... (Review)
Review
Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late-stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme-catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late-stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development.
Topics: Amides; Biocatalysis; Enzymes
PubMed: 33453143
DOI: 10.1002/anie.202014931 -
Journal of the American Chemical Society Jul 2017Quantitative information about amide interactions in water is needed to understand their contributions to protein folding and amide effects on aqueous processes and to...
Quantitative information about amide interactions in water is needed to understand their contributions to protein folding and amide effects on aqueous processes and to compare with computer simulations. Here we quantify interactions of urea, alkylated ureas, and other amides by osmometry and amide-aromatic hydrocarbon interactions by solubility. Analysis of these data yields strengths of interaction of ureas and naphthalene with amide spO, amide spN, aliphatic spC, and amide and aromatic spC unified atoms in water. Interactions of amide spO with urea and naphthalene are favorable, while amide spO-alkylurea interactions are unfavorable, becoming more unfavorable with increasing alkylation. Hence, amide spO-amide spN interactions (proposed n-σ* hydrogen bond) and amide spO-aromatic spC (proposed n-π*) interactions are favorable in water, while amide spO-spC interactions are unfavorable. Interactions of all ureas with spC and amide spN are favorable and increase in strength with increasing alkylation, indicating favorable spC-amide spN and spC-spC interactions. Naphthalene results show that aromatic spC-amide spN interactions in water are unfavorable while spC-spC interactions are favorable. These results allow interactions of amide and hydrocarbon moieties and effects of urea and alkylureas on aqueous processes to be predicted or interpreted in terms of structural information. We predict strengths of favorable urea-benzene and N-methylacetamide interactions from experimental information to compare with simulations and indicate how amounts of hydrocarbon and amide surfaces buried in protein folding and other biopolymer processes and transition states can be determined from analysis of urea and diethylurea effects on equilibrium and rate constants.
Topics: Amides; Hydrocarbons, Aromatic; Molecular Structure; Naphthalenes; Solubility; Urea; Water
PubMed: 28678492
DOI: 10.1021/jacs.7b03261 -
Molecules (Basel, Switzerland) Oct 2018Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide... (Review)
Review
Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide bonds is their ability to form resonating structures, thus, they are highly stable and adopt particular three-dimensional structures, which, in turn, are responsible for their functions. The main focus of this review article is to report the methodologies for the activation of the unactivated amide bonds present in biomolecules, which includes the enzymatic approach, metal complexes, and non-metal based methods. This article also discusses some of the applications of amide bond activation approaches in the sequencing of proteins and the synthesis of peptide acids, esters, amides, and thioesters.
Topics: Acids; Amides; Biological Products; Esters; Molecular Conformation
PubMed: 30322008
DOI: 10.3390/molecules23102615 -
Molecules (Basel, Switzerland) Jan 2019Over the past few decades, transition metal catalysis has witnessed a rapid and extensive development. The discovery and development of cross-coupling reactions is... (Review)
Review
Over the past few decades, transition metal catalysis has witnessed a rapid and extensive development. The discovery and development of cross-coupling reactions is considered to be one of the most important advancements in the field of organic synthesis. The design and synthesis of well-defined and bench-stable transition metal pre-catalysts provide a significant improvement over the current catalytic systems in cross-coupling reactions, avoiding excess use of expensive ligands and harsh conditions for the synthesis of pharmaceuticals, agrochemicals and materials. Among various well-defined pre-catalysts, the use of Pd(II)-NHC, particularly, provided new avenues to expand the scope of cross-coupling reactions incorporating unreactive electrophiles, such as amides and esters. The strong σ-donation and tunable steric bulk of NHC ligands in Pd-NHC complexes facilitate oxidative addition and reductive elimination steps enabling the cross-coupling of broad range of amides and esters using facile conditions contrary to the arduous conditions employed under traditional catalytic conditions. Owing to the favorable catalytic activity of Pd-NHC catalysts, a tremendous progress was made in their utilization for cross-coupling reactions via selective acyl C⁻X (X=N, O) bond cleavage. This review highlights the recent advances made in the utilization of well-defined pre-catalysts for C⁻C and C⁻N bond forming reactions via selective amide and ester bond cleavage.
Topics: Amides; Catalysis; Chemistry Techniques, Synthetic; Esters; Ligands; Molecular Structure; Oxidation-Reduction; Palladium
PubMed: 30634382
DOI: 10.3390/molecules24020215 -
Molecules (Basel, Switzerland) Aug 2018Highly reactive arynes activate the N⁻C and C=O bonds of amide groups under transition metal-free conditions. This review highlights the insertion of arynes into the... (Review)
Review
Highly reactive arynes activate the N⁻C and C=O bonds of amide groups under transition metal-free conditions. This review highlights the insertion of arynes into the N⁻C and C=O bonds of the amide group. The insertion of arynes into the N⁻C bond gives the unstable four-membered ring intermediates, which are easily converted into -disubstituted arenes. On the other hand, the selective insertion of arynes into the C=O bond is observed when the sterically less-hindered formamides are employed to give a reactive transient intermediate. Therefore, the trapping reactions of transient intermediates with a variety of reactants lead to the formation of oxygen atom-containing heterocycles. As relative functional groups are activated, the reactions of arynes with sulfinamides, phosphoryl amides, cyanamides, sulfonamides, thioureas, and vinylogous amides are also summarized.
Topics: Amides; Chemistry Techniques, Synthetic; Metals
PubMed: 30150534
DOI: 10.3390/molecules23092145 -
Angewandte Chemie (International Ed. in... Dec 2022In contrast to ketones and carboxylic esters, amides are classically seen as comparatively unreactive members of the carbonyl family, owing to their unique structural... (Review)
Review
In contrast to ketones and carboxylic esters, amides are classically seen as comparatively unreactive members of the carbonyl family, owing to their unique structural and electronic features. However, recent decades have seen the emergence of research programmes focused on the selective activation of amides under mild conditions. In the past four years, this area has continued to rapidly develop, with new advances coming in at a fast pace. Several novel activation strategies have been demonstrated as effective tools for selective amide activation, enabling transformations that are at once synthetically useful and mechanistically intriguing. This Minireview comprises recent advances in the field, highlighting new trends and breakthroughs in what could be called a new age of amide activation.
Topics: Amides; Catalysis; Esters; Ketones
PubMed: 36124856
DOI: 10.1002/anie.202212213 -
ChemSusChem Mar 2022Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small-molecule active pharmaceutical... (Review)
Review
Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small-molecule active pharmaceutical ingredients, in linear or cyclic oligo- and polypeptidic actives, including pseudopeptides, has led to the development of dedicated synthetic approaches for the formation of amide bonds starting from, if necessary, suitably protected amino acids. While the use of solid supported reagents is common in traditional peptide synthesis, similar approaches targeting amide bond formation in continuous-flow mode took off more significantly, after a first publication in 2006, only a couple of years ago. Most efforts rely upon the transition of traditional approaches in flow mode, or the combination of solid-phase peptide synthesis principles with flow chemistry, and advantages are mainly seen in improving space-time yields. This Review summarizes and compares the various approaches in terms of basic amide formation, peptide synthesis, and pseudopeptide generation, describing the technological approaches and the advantages that were generated by the specific flow approaches. A final discussion highlights potential future needs and perspectives in terms of greener and more sustainable syntheses.
Topics: Amides; Amino Acids; Chemistry Techniques, Synthetic; Peptides; Solid-Phase Synthesis Techniques
PubMed: 35015338
DOI: 10.1002/cssc.202102708 -
The Journal of Physical Chemistry... Jul 2022The origin of the peculiar amide spectral features of proteins in aqueous solution is investigated, by exploiting a combined theoretical and experimental approach to...
The origin of the peculiar amide spectral features of proteins in aqueous solution is investigated, by exploiting a combined theoretical and experimental approach to study UV Resonance Raman (RR) spectra of peptide molecular models, namely -acetylglycine--methylamide (NAGMA) and -acetylalanine--methylamide (NALMA). UVRR spectra are recorded by tuning Synchrotron Radiation at several excitation wavelengths and modeled by using a recently developed multiscale protocol based on a polarizable QM/MM approach. Thanks to the unparalleled agreement between theory and experiment, we demonstrate that specific hydrogen bond interactions, which dominate hydration dynamics around these solutes, play a crucial role in the selective enhancement of amide signals. These results further argue the capability of vibrational spectroscopy methods as valuable tools for refined structural analysis of peptides and proteins in aqueous solution.
Topics: Amides; Hydrogen Bonding; Peptides; Proteins; Spectrum Analysis, Raman; Water
PubMed: 35770492
DOI: 10.1021/acs.jpclett.2c01277