Trimethylacetic Anhydride Research Articles

Potassium tert-Butoxide Facilitated Amination of Carboxylic Acids with N,N-Dimethylformamide

AbstractHerein a practical and efficient potassium tert-butoxide (KO t Bu)-facilitated amination of carboxylic acids with N,N-dimethylamine is described. In the presence of catalytic amount of KO t Bu, a variety of aliphatic and aromatic carboxylic acids are transformed to N,N-dimethylamides using DMF as the dimethylamine reagent with the assistance of trimethylacetic anhydride. The applicability of this protocol is demonstrated by late-stage dimethylamidation of complex drug molecules. A plausible reaction mechanism involving KO t Bu-facilitated in situ amine generation from formamide decomposition and anhydride-mediated condensation is proposed on the basis of mechanistic investigations.

Trimethylacetic Anhydride–Based Derivatization Facilitates Quantification of Histone Marks at the MS1 Level

Histone post-translational modifications (hPTMs) are epigenetic marks that strongly affect numerous processes, including cell cycling and protein interactions. They have been studied by both antibody- and MS-based methods for years, but the analyses are still challenging, mainly because of the diversity of histones and their modifications arising from high contents of reactive amine groups in their amino acid sequences. Here, we introduce use of trimethylacetic anhydride (TMA) as a new reagent for efficient histone derivatization, which is a requirement for bottom–up proteomic hPTM analysis. TMA can derivatize unmodified amine groups of lysine residues and amine groups generated at peptide N-termini by trypsin digestion. The derivatization is facilitated by microwave irradiation, which also reduces incubation times to minutes. We demonstrate that histone derivatization with TMA reliably provides high yields of fully derivatized peptides and thus is an effective alternative to conventional methods. TMA afforded more than 98% and 99% labeling efficiencies for histones H4 and H3, respectively, thereby enabling accurate quantification of peptide forms. Trimethylacetylation substantially improves chromatographic separation of peptide forms, which is essential for direct quantification based on signals extracted from MS1 data. For this purpose, software widely applied by the proteomics community can be used without additional computational development. Thorough comparison with widely applied propionylation highlights the advantages of TMA-based histone derivatization for monitoring hPTMs in biological samples.

Discrete Neutral Niobium Cluster Units in Compounds of the Type [Nb6Cl14L4] with L = O or N Donor Ligand

Six new hexanuclear niobium cluster compounds of the general formula [Nb6Cl14L4]·x(solvent molecule) [L = neutral O or N donor ligand, x = 0–2.5; pyrimidine (1), 1‐methyl imidazole (2), isobutyronitrile (3), isopropyl alcohol (4), triphenylphosphine oxide (5), dimethyl sulfoxide (6)] were prepared. The syntheses were carried out by dehydration of the precursor [Nb6Cl14(H2O)4]·4H2O with different water scavangers, like acetic anhydride, trimethyl acetic anhydride and diethylcarbonate in the presence of the corresponding neutral ligand. The structures are determined by single‐crystal X‐ray diffraction. The specific bonding situations of the ligands to the [Nb6Cl12]2+ cluster cores are compared and discussed. The phenomenon of the observed M6 distortion is explained and interpreted based on the matrix effect and the terminal ligand effect. In addition, other interactions between the cluster units, such as hydrogen bonding and π–π stacking are discussed.

Dual-drug loaded nanoformulation with a galactosamine homing moiety for liver-targeted anticancer therapy.

Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), Pt(IV) prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The Pt(IV) prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.

Thermodynamic Properties and Ideal-Gas Enthalpies of Formation for trans-Methyl Cinnamate, α-Methyl Cinnamaldehyde, Methyl Methacrylate, 1-Nonyne, Trimethylacetic Acid, Trimethylacetic Anhydride, and Ethyl Trimethyl Acetate

The results of a study aimed at improvement of group-contribution methodology for estimation of thermodynamic properties of organic substances are reported. Specific weaknesses where particular group-contribution terms were unknown, or estimated because of lack of experimental data, are addressed by experimental studies of enthalpies of combustion in the condensed phase, vapor-pressure measurements, and differential scanning calorimetric heat-capacity measurements. Ideal-gas and condensed-phase enthalpies of formation of trans-methyl cinnamate, α-methyl cinnamaldehyde, methyl methacrylate, 1-nonyne, trimethylacetic acid, trimethylacetic anhydride, and ethyl trimethyl acetate are reported. Enthalpies of fusion were determined for trans-methyl cinnamate and trimethylacetic acid. Two-phase (solid + vapor) or (liquid + vapor) heat capacities were determined from 300 K to the critical region or earlier decomposition temperature for all the compounds. For ethyl trimethyl acetate, the values of the critical temp...

Observation and elimination of N-acetylation of oligonucleotides prepared using fast-deprotecting phosphoramidites and ultra-mild deprotection

Commercially available ‘fast-deprotecting’ phosphoramidites are useful for synthesizing oligonucleotides containing alkali-sensitive nucleotides. However, N-acetylated oligonucleotides were observed during solid-phase synthesis using ‘fast-deprotecting’ phosphoramidites in conjunction with K 2CO 3/MeOH (‘ultra-mild’) deprotection. Transamidation was localized at deoxyguanosine, which is protected as its isopropylphenoxyacetyl amide. Substitution of trimethylacetic anhydride for acetic anhydride and appropriate modification of the automated synthesis cycles eliminated this problem.

パラジウム錯体によるカルボン酸無水物の炭素‐酸素結合活性化とその応用

Acyclic and cyclic carboxylic anhydrides oxidatively add to zerovalent palladium complexes having tertiary phosphines with carbon-oxygen bond cleavage to give corresponding acyl (carboxylato) palladium complexes, which subsequently react with atmospheric dihydrogen at room temperature to form aldehydes and carboxylic acids. Application of these results led us to the discovery of novel aldehyde synthesis by hydrogenation of carboxylic anhydrides catalyzed by palladium complexes. Furthermore we have developed atom-efficient and environmentally benign, direct hydrogenation of carboxylic acids to corresponding aldehydes in the presence of trimethylacetic anhydride catalyzed by palladium complexes.

Thermal behaviour of some homogeneously esterified products of high α -cellulose pulps of fast growing plant species

High α -cellulose pulps obtained from fast growing plant species Leucaena leucocephala and Hibiscus cannabinus were esterified with trimellitic anhydride (TMA), phthalic anhydride (PTA) and trimethyl acetic anhydride (TMAA), following a homogeneous reaction procedure. The degree of substitution achieved was found to vary, up to 2.56, depending on the reaction conditions. Thermal decomposition was studied by a differential thermogravimetry at three heating rates 5, 10 and 20°C min −1 in static air. The kinetic parameters were evaluated using the generalized equation of Coats and Redfern. The thermal stabilities of the esters were found to vary in the order TMA > PTA > TMAA. The decomposition process was found to conform to first order weight loss kinetics, and the activation energies of the respective esters at 5°Cmin −1 heating rate were 308.11, 194.98 and 213.00 kJ mol −1 respectively.

The Hydrolysis of Carboxylic Anhydrides. V.1,2 The Acid Hydrolysis of Acetic and Trimethylacetic Anhydride

The Hydrolysis of Carboxylic Anhydrides. V.^1,2 The Acid Hydrolysis of Acetic and Trimethylacetic Anhydride