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The Journal of Organic Chemistry Aug 2015The SNAr reaction of 2,4-dichloropyrimidines, further substituted with an electron-withdrawing substituent at C-5, has selectivity for substitution at C-4. Here we...
The SNAr reaction of 2,4-dichloropyrimidines, further substituted with an electron-withdrawing substituent at C-5, has selectivity for substitution at C-4. Here we report that tertiary amine nucleophiles show excellent C-2 selectivity. In situ N-dealkylation of an intermediate gives the product that formally corresponds to the reaction of a secondary amine nucleophile at C-2. This reaction is practical (fast under simple reaction conditions, with good generality for tertiary amine structure and moderate to excellent yields) and significantly expands access to pyrimidine structures.
Topics: Amination; Amines; Catalysis; Molecular Structure; Pyrimidines; Stereoisomerism
PubMed: 26154983
DOI: 10.1021/acs.joc.5b01044 -
Chembiochem : a European Journal of... Jan 2020A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild...
A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29-75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.
Topics: Amination; Amines; Laccase; Molecular Structure; Propanols; Stereoisomerism; Transaminases
PubMed: 31513330
DOI: 10.1002/cbic.201900473 -
Angewandte Chemie (International Ed. in... Jan 2023An efficient strategy for preventing the β-hydride elimination of alkylpalladium species by ligation of the palladium with adjacent amino-group was developed, which...
An efficient strategy for preventing the β-hydride elimination of alkylpalladium species by ligation of the palladium with adjacent amino-group was developed, which enabled a novel palladium-catalyzed ring-closing aminoalkylative amination of unactivated aminoenynes. The reaction is amenable to aminals, as well as aliphatic aldehydes with secondary amines, which provides straightforward access to structurally diverse exocyclic allenic amines bearing 5 to 12-membered N-heterocycles. With chiral phosphoramidite-ligated palladium complex as the catalyst, an enantioselective variant was achieved with up to 93 % ee. Simultaneously, synthetic transformations of the chiral products were also conducted to afford structurally unique spirodiamines including one pharmaceutically active molecule via axial-to-central chirality transfer.
Topics: Amination; Palladium; Molecular Structure; Amines; Catalysis; Stereoisomerism
PubMed: 36409522
DOI: 10.1002/anie.202215325 -
Methods in Molecular Biology (Clifton,... 2022On-DNA reductive amination (on-DNA aldehyde with amine building blocks) and alkylation (on-DNA amine with aldehyde building blocks) are robust ways to form C-N bond. The...
On-DNA reductive amination (on-DNA aldehyde with amine building blocks) and alkylation (on-DNA amine with aldehyde building blocks) are robust ways to form C-N bond. The large sets of commercially available aldehyde and amine building blocks make reductive amination and alkylation widely used in DEL synthesis.
Topics: Aldehydes; Alkylation; Amination; Amines; DNA
PubMed: 36083540
DOI: 10.1007/978-1-0716-2545-3_5 -
Organic & Biomolecular Chemistry Aug 2022A two-component reductive amination approach to the synthesis of peptide macrocycles is reported which leverages the inherent reactivity of proteinogenic amine...
A two-component reductive amination approach to the synthesis of peptide macrocycles is reported which leverages the inherent reactivity of proteinogenic amine nucleophiles. Unprotected peptides bearing α-amine and side chain amine motifs undergo two-fold reductive amination reactions with 2,6-pyridinedialdehyde linkers in aqueous media to afford macrocyclic peptide products with backbone embedded pyridine motifs. Dialdehyde staples bearing valuable azide and alkyne handles also enable the post-cyclisation modification of peptides using copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry.
Topics: Alkynes; Amination; Amines; Azides; Catalysis; Copper; Cycloaddition Reaction; Peptides
PubMed: 35621075
DOI: 10.1039/d2ob00782g -
Chemical Communications (Cambridge,... Jul 2022The base-mediated anti-Markovnikov hydroamination of functionally varied styrenes with amino-substituted pyridine, quinoline, pyrimidine, pyrazine, and phenanthridine...
The base-mediated anti-Markovnikov hydroamination of functionally varied styrenes with amino-substituted pyridine, quinoline, pyrimidine, pyrazine, and phenanthridine with excellent regioselectivity has been described. Double hydroamination was observed chemoselectively on the secondary amine, leaving the primary amine intact. Experimental evidence suggests that the proposed reaction involves the nucleophilic addition of the aminopyridyl radical onto vinyl arenes a single electron transfer.
Topics: Amination; Amines; Catalysis; Molecular Structure; Styrenes; Transition Elements
PubMed: 35796310
DOI: 10.1039/d2cc02781j -
ChemMedChem Jun 2008A structure-activity relationship around the amine group of the ambruticin VS series has been developed for antifungal activity. It was shown that the amine can be...
A structure-activity relationship around the amine group of the ambruticin VS series has been developed for antifungal activity. It was shown that the amine can be alkylated through reductive amination without loss of potency. However, if it is converted into either an amide, carbamate, or urea, a significant loss of potency is observed. Of the alkyl amines, small nonpolar groups are optimal for both potency and oral bioavailability. As a result of this study, one compound (KOS-2079) was taken into an animal efficacy model with success.
Topics: Alkylation; Amination; Amines; Animals; Antifungal Agents; Biological Availability; Coccidioides; Drug Design; Mice; Microbial Sensitivity Tests; Molecular Conformation; Pyrans; Stereoisomerism; Structure-Activity Relationship
PubMed: 18307190
DOI: 10.1002/cmdc.200800008 -
Analytical Chemistry Nov 2018Surface chemistry is a critical factor for determining the behavior of a nanomaterial after incorporation in composites, devices, and biomedical products, and is also...
Surface chemistry is a critical factor for determining the behavior of a nanomaterial after incorporation in composites, devices, and biomedical products, and is also important for nanotoxicology studies. We have developed an optimized protocol for dissolution of aminated silicas and determination of functional-group contents by quantitative H NMR (qNMR) analysis of the released amines. A number of variables were optimized for the dissolution protocol, including the base concentration, mass of silica, time, temperature, and method of sample agitation, in order to achieve adequate NMR signals for quantification. The protocol was tested using nanoparticles from a single commercial supplier with sizes ranging from 20 to 120 nm that were functionalized with 3-aminopropyl groups. Interestingly the batch-to-batch variability for some sizes of these aminated silicas was as high as 50%. Amine contents measured by a ninhydrin colorimetric assay were typically ∼20% lower than those measured by qNMR, consistent with measurement of only ninhydrin-reagent accessible amines. The dissolution-qNMR protocol was compatible with aminated silicas from other commercial suppliers, and in these cases, an even larger variability in surface coverage was observed. Silica nanoparticles with longer-chain amines and variable amine loadings were synthesized to demonstrate the ability to quantify amines with more complex structures and to assess the limit of quantification for the dissolution-qNMR method. Finally, the stability of the aminated nanoparticles was examined. Loss of 3-aminopropyl groups occurred in water at room temperature and was significantly more rapid at higher temperatures. Amine loss increased with increasing surface coverage and was slower for long-chain amines, consistent with studies of amine stability on planar silica. Overall, this work highlights the importance of developing methods for quantifying surface functionalization, particularly given the variability in surface coverage for commercial samples, and for ensuring that the amine group is stable under its usage conditions.
Topics: Amination; Hydrolysis; Nanoparticles; Particle Size; Propylamines; Proton Magnetic Resonance Spectroscopy; Silicon Dioxide; Temperature
PubMed: 30372033
DOI: 10.1021/acs.analchem.8b02803 -
Biotechnology and Bioengineering Oct 2023Opines and opine-type chemicals are valuable natural products with diverse biochemical roles, and potential synthetic building blocks of bioactive compounds. Their... (Review)
Review
Opines and opine-type chemicals are valuable natural products with diverse biochemical roles, and potential synthetic building blocks of bioactive compounds. Their synthesis involves reductive amination of ketoacids with amino acids. This transformation has high synthetic potential in producing enantiopure secondary amines. Nature has evolved opine dehydrogenases for this chemistry. To date, only one enzyme has been used as biocatalyst, however, analysis of the available sequence space suggests more enzymes to be exploited in synthetic organic chemistry. This review summarizes the current knowledge of this underexplored enzyme class, highlights key molecular, structural, and catalytic features with the aim to provide a comprehensive general description of opine dehydrogenases, thereby supporting future enzyme discovery and protein engineering studies.
Topics: Amines; Amination; Amino Acids; Keto Acids; Oxidoreductases; Biocatalysis; Stereoisomerism
PubMed: 37334502
DOI: 10.1002/bit.28469 -
Topics in Current Chemistry (Cham) Mar 2020Aromatic amines belong to a highly important class of organic compounds which are found in various natural products, functional materials, and pharmaceutical agents.... (Review)
Review
Aromatic amines belong to a highly important class of organic compounds which are found in various natural products, functional materials, and pharmaceutical agents. Their prevalence has sparked continuing interest in the development of highly efficient and environmentally benign synthetic strategies for the construction of these compounds. Cross-dehydrogenative coupling reactions between two unmodified C(X)-H bonds have recently emerged as a versatile and powerful strategy for the fabrication of new C(X)-C(X) bonds. In this context, several procedures have been reported for the synthesis of aromatic amines through the direct amination of aromatic C-H bonds with free amines. This review highlights recent advances and progress in this appealing research arena, with special emphasis on the mechanistic features of the reactions.
Topics: Amination; Amines; Carbon; Humans; Hydrogen; Molecular Structure
PubMed: 32236795
DOI: 10.1007/s41061-020-0300-1