Search results for "METHYLATION"
showing 10 items of 607 documents
A three-component Mannich-type condensation leading to phosphinic dipeptides—extended transition state analogue inhibitors of aminopeptidases
2011
Abstract N-Protected α-aminoalkylphosphinic acids bearing a P–H function were found to be novel practical building blocks in three-component condensations with formaldehyde and secondary amines (amino acids). Such Mannich-type N -phosphonomethylation is a common approach for phosphorus acid derived substrates and leads to multifunctional (phosphonic/amino/carboxylic) compounds of diverse relevance. The utility of this reaction was examined for construction, in a single synthetic step, of advanced phosphinic pseudodipeptides designed to act as extended transition state analogue inhibitors of selected aminopeptidases. Phosphinomethylation of primary amino acids was less efficient and yielded …
The conformation cis of N-acetyl-N-methyl-α,β-dehydroalanine N′-methylamide and saturated analogues
2007
A series of three homologous amino acids derivatives: N-acetyl-N-methyl-α,β–dehydroalanine N′-methylamide (1), N-acetyl-N-methyl-L-alanine N′-methylamide (2), and N-acetyl-N-methyl-DL-alanine N′-methylamide have been synthesised. The racemic species undergoes spontaneous separation into L and D-enantiomers. From these two chiral forms, the structure of L-enantiomer (3) was analysed. The molecules of 1 – 3 adopt the cis arrangement of the N-terminal amide bond. The molecular conformations are similar for 1 (φ, ψ = 94.6(1)°, −1.7(1)°) and 3 (φ, ψ = 111.5(1)°, −23.8(1)°), and also 2 (φ, ψ = −114.8(2)°, 29.5(2)°), if inversion through the chiral C2 carbon is considered. They are stabilised by i…
N-Methyldehydroamino acids promote a configuration cis of N-methylamide bond
2008
Abstract Dehydroamino acids with a methylated N-terminal tertiary amide bond occur in natural small cyclic peptide toxins. To investigate their conformational preferences a systematic theoretical analysis was performed on N ′-methylamides of N -acetyl- N -methyldehydroamino acids (Ac-Δ(Me)Xaa-NHMe, where Xaa = ( Z )-Abu, ( E )-Abu, Val, ( Z )-Phe, and ( E )-Phe) considering the configuration trans and cis of the tertiary amide bond. The ϕ , ψ potential energy surfaces were calculated at the B3LYP/6-31+G ∗∗ //HF/3-21G level with inclusion of the solvent (water) effect (SCRF method). The conformers localised were fully optimised at the B3LYP/6-31+G ∗∗ in vacuo. The accessible areas of the pot…
Epigenetics, oxidative states and diabetes
2020
Abstract Although controlling a wide range of physiological cell functions, redox states unbalance during inflammation toward oxidative stress. Specific regions of our genome are extremely sensitive to both oxygen and reactive oxygen species, therefore modulating gene transcription in response to this specific epigenetic effect. Additional epigenetic mechanisms may include the alteration of the methylation states of DNA, protein and lipid nitration or modulation of specific microRNAs. A crucial role in finely tuning redox states is also played by mitochondria, where oxidative phosphorylation is epigenetically controlled. Diabetes, the most considerable “epigenetic” clinical disorder, exacer…
Vergleichende Untersuchung zur Diastereoselektivität derO-Methylierung von sterisch behinderten β-Ketocarbonsäureestern und ihren Enolen
1990
Diastereoselectivity of the O-Methylation of Sterically Hindered β-Ketocarboxylates and Their Enols The enols 1a, b, and 1c, which exists almost completely in the keto form, have been methylated at the oxygen atom with diazomethane. The regioselective reaction can be catalyzed by methanol, but may loose in that case the diastereoselectivity. A comparison with the methylation of the enolates by iodomethane is discussed.
Bridge-Clamp Bis(tetrazine)s with [N] 8 π-Stacking Interactions and Azido- s -Aryl Tetrazines: Two Classes of Doubly Clickable Tetrazines
2020
Click chemistry at a tetrazine core is useful for bioorthogonal labeling and crosslinking. Introduced here are two new classes of doubly clickable s-aryl tetrazines synthesized by Cu-catalyzed cross-coupling. Homocoupling of o-brominated s-aryl tetrazines leads to bis(tetrazine)s structurally characterized by tetrazine cores arranged face-to-face. [N]8 π-stacking interactions are essential to the conformation. Upon inverse electron demand Diels-Alder (iEDDA) cycloaddition, the bis(tetrazine)s produce a unique staple structure. The o-azidation of s-aryl tetrazines introduces a second proximal intermolecular clickable function that leads to double click chemistry opportunities. The stepwise i…
Translational adaptation to heat stress is mediated by 5-methylcytosine RNA modification in Caenorhabditis elegans
2020
ABSTRACTMethylation of carbon-5 of cytosines (m5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, usingCaenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non-essential. We determined the localisation and enzymatic specificity of m5C sites in RNAin vivoand showed that animals devoid of m5C are sensitive to temperature stress. At the molecular level, we showed that loss of m5C specifically impacts decoding of leucine and p…
Studies on the interaction of phosphate anions with N-functionalised polyaza[n]paracyclophanes: the role of N-methylation.
2004
The synthesis and interaction of N,N',N'',N'''-tetramethyl-2,6,9,13-tetraaza[14]paracyclophanes (B323Me(4)) with nucleotides and inorganic phosphates is described. An easy methodology is used to define thermodynamic selectivity. The interaction of B323Me4 and ATP has been monitored by (1)H, (31)P NMR and by molecular mechanics, ruling out the possibility of the participation of pi-stacking interactions. Results show that N-methylation is accompanied by a strong increase in the interaction of the resulting macrocycle with ATP.
Synthesis of pillar[7]arene
2012
Abstract The first synthesis of pillar[7]arene is reported with two methods. Method A: the FeCl 3 -catalyzed condensation reaction of 1,4-dimethoxybenzene ( 1 ) with paraformaldehyde in CHCl 3 gave dimethoxypillar[7]arene ( 3 ). Method B: the p -toluenesulfonic acid catalyzed condensation reaction of 2,5-bis(benzyloxymethyl)-1,4-dimethoxybenzene ( 2 ) in CH 2 Cl 2 gave compound 3 . Demethylation of 3 with BBr 3 gave pillar[7]arene ( 4 ). The pillar[7]arene might be a perspective macrocyclic host in host–guest chemistry.
ChemInform Abstract: Synthesis and Spectroscopic Characterizations of Both 1-Ethyl-4,8- dihydro-10-methoxy-3-methyl-8-R1-6-R2-dipyrazolo(3,4-b:4′,3′-…
2010
The non-selective methylation of compounds 3a-d using ethereal diazomethane, allowed the synthesis of isomers 4 and 5 which were useful intermediates for the preparation, by a simple approach, of the title compounds 7 and 9. A complete assignment of the chemical shifts to the carbon atoms of the compounds 7 and 9 was performed by different nmr experiments, such as DEPT and XHDEPT for onebond CH correlations and COLOC experiments for long-range C-H correlations.