Trifluoroacetate Derivatives Research Articles

Synthesis of scaberol C amino acid ester derivatives with anti-cancer activity

A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC50), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.

Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases.

The Aurora Kinase family (AKI) is composed of serine-threonine protein kinases involved in the modulation of the cell cycle and mitosis. These kinases are required for regulating the adherence of hereditary-related data. Members of this family can be categorized into aurora kinase A (Ark-A), aurora kinase B (Ark-B), and aurora kinase C (Ark-C), consisting of highly conserved threonine protein kinases. These kinases can modulate cell processes such as spindle assembly, checkpoint pathway, and cytokinesis during cell division. The main aim of this review is to explore recent updates on the oncogenic signaling of aurora kinases in chemosensitive/chemoresistant cancers and to explore the various medicinal chemistry approaches to target these kinases. We searched Pubmed, Scopus, NLM, Pubchem, and Relemed to obtain information pertinent to the updated signaling role of aurora kinases and medicinal chemistry approaches and discussed the recently updated roles of each aurora kinases and their downstream signaling cascades in the progression of several chemosensitive/chemoresistant cancers; subsequently, we discussed the natural products (scoulerine, Corynoline, Hesperidin Jadomycin-B, fisetin), and synthetic, medicinal chemistry molecules as aurora kinase inhibitors (AKIs). Several natural products' efficacy was explained as AKIs in chemosensitization and chemoresistant cancers. For instance, novel triazole molecules have been used against gastric cancer, whereas cyanopyridines are used against colorectal cancer and trifluoroacetate derivatives could be used for esophageal cancer. Furthermore, quinolone hydrazine derivatives can be used to target breast cancer and cervical cancer. In contrast, the indole derivatives can be preferred to target oral cancer whereas thiosemicarbazone-indole could be used against prostate cancer, as reported in an earlier investigation against cancerous cells. Moreover, these chemical derivatives can be examined as AKIs through preclinical studies. In addition, the synthesis of novel AKIs through these medicinal chemistry substrates in the laboratory using in silico and synthetic routes could be beneficial to develop prospective novel AKIs to target chemoresistant cancers. This study is beneficial to oncologists, chemists, and medicinal chemists to explore novel chemical moiety synthesis to target specifically the peptide sequences of aurora kinases in several chemoresistant cancer cell types.

Use of Trifluoro-Acetate Derivatives for GC-MS and GC-MS/MS Quantification of Trace Amounts of Stera-3β,5α,6β-Triols (Tracers of Δ5-Sterol Autoxidation) in Environmental Samples.

Stera-3β,5α,6β-triols make useful tracers of the autoxidation of Δ5-sterols. These compounds are generally analyzed using gas chromatography-mass spectrometry (GC-MS) after silylation. Unfortunately, the 5α hydroxyl groups of these compounds, which are not derivatized by conventional silylation reagents, substantially alter the chromatographic properties of these derivatives, thus ruling out firm quantification of trace amounts. In this work, we developed a derivatization method (trifluoroacetylation) that enables derivatization of the three hydroxyl groups of 3β,5α,6β-steratriols. The derivatives thus formed present several advantages over silyl ethers: (i) better stability, (ii) shorter retention times, (iii) better chromatographic properties and (iv) mass spectra featuring specific ions or transitions that enable very low limits of detection in selected ion monitoring (SIM) and multiple reaction monitoring (MRM) modes. This method, validated with cholesta-3β,5α,6β-triol, was applied to several environmental samples (desert dusts, marine sediments and particulate matter) and was able to quantify trace amounts of 3β,5α,6β-steratriols corresponding to several sterols: not only classical monounsaturated sterols (e.g., cholesterol, campesterol and sitosterol) but also, and for the first time, di-unsaturated sterols (e.g., stigmasterol, dehydrocholesterol and brassicasterol).

Microwave and Computational Study of Pivalic Sulfuric Anhydride and the Pivalic Acid Monomer: Mechanistic Insights into the RCOOH + SO3 Reaction.

The microwave spectrum of pivalic sulfuric anhydride, (CH3)3CCOOSO2OH (PivSA), has been observed by rotational spectroscopy. The compound was formed by the reaction of SO3 with (CH3)3CCOOH (pivalic acid) in a supersonic jet in a manner analogous to that previously observed with other carboxylic acids. Computational analysis indicates that the reaction is best described as a pericyclic process coupled with a 60° rotation of the t-butyl group. Product formation can occur through either a sequential (two-step) or a concerted (one-step) pathway. The former involves an internal rotation of the t-butyl group through a 0.11 kcal/mol barrier followed by the pericyclic reaction that joins the moieties. The latter passes through a second-order saddle point in which the internal rotation and pericyclic reaction occur simultaneously. This path is the most energetically favorable, as the zero-point corrected energy at the saddle point structure is 0.16 kcal/mol below that of a putative (CH3)3CCOOH-SO3 precursor complex. Additional computational work involving a series of carboxylic acids is reported, which explores the effects of gas-phase acidity and basicity of the RCOOH reactant on reaction energetics. These calculations, together with prior experimental and theoretical studies of the acetic and trifluoroacetic derivatives, demonstrate that the basicity of the carbonyl oxygen, not the acidity of the COOH proton, is the important driving factor for the reaction. As a precursor to the experimental work on the title molecule, microwave spectra of the parent and OD forms of the pivalic acid monomer were recorded and are reported here as well. A convenient synthesis of SO3 is also described.

Detection of exogenous sugars in pineapple juice using compound-specific stable hydrogen isotope analysis

An improved procedure for determining 2H/1H isotope ratios, using gas chromatography-isotope ratio mass spectrometry, has been used to detect the addition of exogenous C4-plant-derived sugars to pineapple juice. Isotopic techniques are commonly used to identify the addition of low-cost sugars to fruit juices and are difficult to subvert as it is not economically viable to change the isotopic ratios of the sugars. However, the addition of cane sugar to pineapple juice has presented a significant challenge that is only detected by site-specific 13C analysis of the methyl and methylene positions of ethanol derived from pineapple sugars, measured by nuclear magnetic resonance. This new GC-IRMS-based procedure utilises the trifluoroacetate derivative of sucrose to allow direct measurement of the carbon-bound non-exchangeable hydrogen. This provides advantages over alternative isotopic methods in terms of analysis time and sensitivity. This feasibility study has demonstrated the potential to reliably differentiate between authentic pineapple juices and those adulterated with commercial beet and cane sucrose.

Stable isotope analysis of non-exchangeable hydrogen in carbohydrates derivatised with N-methyl-bis-trifluoroacetamide by gas chromatography – Chromium silver reduction/High temperature Conversion-isotope ratio mass spectrometry (GC-CrAg/HTC-IRMS)

A novel procedure for the rapid isotope analysis of the carbon-bound non-exchangeable (CBNE) hydrogen in mono and disaccharides has been developed to demonstrate the feasibility of detecting undeclared addition of exogenous sugar products in foods and beverages susceptible to economically motivated adulteration. The procedure utilizes a simple one-step reaction, with the derivatising agent N-methyl-bis-trifluoroacetamide, to substitute the exchangeable hydroxyl-hydrogens with trifluoroacetate derivatives that are sufficiently volatile to be separated and measured by a gas chromatograph coupled to an isotope ratio mass spectrometer. The conversion of the derivatised sugars into the measuring gas is achieved using a high temperature chromium-silver reactor that retains carbon, oxygen and fluorine whilst releasing hydrogen gas for stable isotope measurement. The new procedure has advantages over existing methods in terms of ease of use, analysis time and compound-specific information. Sugars from fruit juice and honey have been measured to demonstrate the feasibility of using this technique.

Preparation and X-ray Crystal Study of Benziodoxaborole Derivatives: New Hypervalent Iodine Heterocycles

A series of heterocyclic compounds containing trivalent iodine, oxygen, and boron in a five-membered ring were prepared and structurally investigated by X-ray crystallography. 1-Chloro-4-fluoro-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol was synthesized by chlorination of 2-fluoro-6-iodophenylboronic acid followed by treatment of the intermediate iododichloride with water. 1-Acetoxy-4-fluoro-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol, 1-acetoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol, and similar 1-substituted trifluoroacetate derivatives of benziodoxaborole were prepared the hypochlorite oxidation of 2-fluoro-6-iodophenylboronic acid or 2-iodophenylboronic acid in acetic or trifluoroacetic acid, respectively. 1-Acetoxy substituted benziodoxaborole can be further converted to the respective trifluoroacetate by treatment with trifluoroacetic acid or to the 1-hydroxy derivative by basic hydrolysis with aqueous NaHCO(3). X-ray structural studies of 1-chloro- and 1-trifluoroacetoxy substituted benziodoxaboroles 13, 17, and 18 have shown the presence of a planar five-membered heterocyclic ring with unusually short endocyclic I-O bond distance of 2.04-2.09 Å. Slow crystallization of 4-fluoro-1-trifluoroacetoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol from methanol resulted in the formation of a tetrameric macrocyclic structure 21 resulting from self-assembly of the initially formed 4-fluoro-1,3-dimethoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol. Structural parameters of the five-membered iodoxoborol ring, such as the planar geometry and the short B-O and O-I bonds lengths in 13, 17, and 18 compared to those in 21 and known benziodoxoles are indicative of partially aromatic character of this ring. Density functional theory (DFT) predicted NIST (0) and NIST (1) indexes for 1-chloro- and 1-trifluoroacetoxy substituted benziodoxaboroles, however, are indicative of significantly lower aromaticity compared to the classic aromatic systems.

Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenylalkylamine designer drugs, such as 3,4‐methylenedioxymethamphetamine (MDMA), 3,4‐methylenedioxyethylamphetamine (MDEA), N‐methyl‐1‐(3,4‐methylenedioxyphenyl)‐2‐butanamine (MBDB), 3,4‐methylenedioxyamphetamine (MDA), and 3,4‐(methylenedioxyphenyl)‐2‐butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity‐5 fused silica capillary column with a poly (5% diphenyl‐95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to α‐cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxypropane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

ChemInform Abstract: Novel Cations and Molecules from Phosphaalkynes, 1H-Phosphirenes and from Tetraphosphacubane

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Synthesis and Reactivity of (η5-Hydroxyalkylcyclohexadienyl)Mn(CO)3 Complexes

(η5-1-Hydroxyalkylcyclohexadienyl)tricarbonylmanganese complexes 3a and 3b have been prepared, and their rearomatization delivered compounds 5 and 6, the first benzylic alcohol derivatives coordinated to the cationic Mn(CO)3 tripod. The structure of 5 has been determined by X-ray crystallography. 1-Hydroxyalkyl 3a, 7, 8, 2-hydroxyalkyl 19, 20, and 3-hydroxyalkyl 25, 26 (η5-cyclohexadienyl)tricarbonylmanganese complexes have been synthesized and studied toward trifluoroacetylation of the hydroxy group when submitted to the action of NEt3 and (CF3CO)2O. Only the 2-hydroxyalkyl-substituted complexes eclipsed by a Mn−CO bond of the Mn(CO)3 tripod gave the expected trifluoroacetate derivatives 21 and 22. For the 1-hydroxyalkyl-substituted complexes, elimination of the trifluoroacetoxy group took place followed by decoordination of the Mn(CO)3 moiety and trifluoroacetylation, giving rise to trifluoromethyltrienones 10, 11, and 12, whose stuctures were established by X-ray analysis. For 3-hydroxyalkyl-substituted complexes, elimination of the trifluoroacetoxy group also occurred, yielding free arenes 27 and 28 by decoordination of the Mn(CO)3 entity.

Immobilized Chiral ortho-Metalated Dirhodium(II) Compounds as Catalysts in the Asymmetric Cyclopropanation of Styrene with Ethyl Diazoacetate

Immobilization of ortho-metalated dirhodium(II) compounds has been achieved by a carboxylate interchange reaction between (M)-Rh2(l-protos)2[(p-XC6H3)P(p-XC6H4)2]2 diastereoisomers and carboxyethylpolystyrene polymer (PS-C6H4(CH2)2CO2H). The immobilized chiral catalysts have been tested in the standard reaction of asymmetric cyclopropanation of styrene with ethyl diazoacetate, giving higher yields than homogeneous chiral trifluoroacetate derivatives, but their diastereo- and enantioselectivities were lower. Some of the immobilized catalysts have proved to be very robust. The catalytic behavior of (M)-Rh2(O2C(CH2)2C6H5)2[(p-XC6H3)P(p-XC6H5)2]2 compounds has been studied as a model for the immobilized catalysts.

Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition

To study the metabolism of cholestanol in patients with cerebrotendinous xanthomatosis (CTX), we measured the cholestanol absorption, the cholesterol and cholestanol turnover, and the tissue content of sterols in two patients. Cholestanol absorption was approximately 5.0%. The rapid exchangeable pool of cholestanol was 233 mg, and the total exchangeable pool was 752 mg. The production rate of cholestanol in pool A was 39 mg/day. [4-14C]cholestanol was detected in the xanthomas, but neither [4-14C]cholestanol nor [4-14C]cholesterol was detected in peripheral nerves biopsied at 49 and 97 days after [4-14C]cholesterol given intravenously. Of the 18 tissues analyzed at biopsy and autopsy, the cholestanol content varied from 0.09 mg/g in psoas muscle to 76 mg/g in a cerebellar xanthoma. With the assumption that the cholestanol-to-cholesterol ratio is 1.0, the relative cholestanol-to-cholesterol ratio varied from 1.0 in plasma and liver to 30.0 in the cerebellar xanthoma; cholestanol was especially high in nerve tissue. Our data indicate that CTX patients absorb cholestanol from the diet. They have a higher than normal cholestanol production rate. Cholestanol was derived from cholesterol. In CTX patients, the blood-brain barrier was intact to the passage of [4-14C]cholesterol and [4-14C]cholestanol. The deposition of large amounts of cholestanol (up to 30% of total sterols in cerebellum) in nerve tissues must have an important role in the neurological symptoms in CTX patients. In view of the intact blood-brain barrier, several other explanations for the large amounts of cholestanol in the brain were postulated.

Synthesis, characterization and molecular structures of Cu(II) and Ba(II) fluorinated carboxylate complexes

Various synthetic routes to Cu(II) and Ba fluorocarboylate derivatives as possible metal organic deposition (MOD) precursors of high Tc superconductors have been explored. The reactions between [Cu 2(TFA) 4] ∞ or Cu 2(TFA) 4(MeOH) 2 and [Ba(TFA) 2] m (TFA = CF 3CO 2) with various O- and N-donor ligands give adducts such as Cu 2(TFA) 4L 2 (L = THF, OHC 2H 4O i Pr), Cu(TFA) 2(pmdeta) (pmdeta = N, N, N′, N″, N″-pentamethyldiethylenetriamine) and Ba(TFA) 2(mdeaH 2) 3 or Ba(TFA) 2(teaH 3) 2 (mdeaH 2 = N-methyldiethanolamine, teaH 3 = triethanolamine). The TFA ligands on copper(II) are quite labile, giving the tetranuclear [Cu(μ,η 2-TFA)(μ 3,η 2-OC 2H 4NMe 2)] 4 · 0.25THF carboxylatoalkoxide by reacting Cu 2(TFA) 4(MeOH) 2 with dimethylaminoethanol. In contrast to the Cu–TFA derivatives, the perfluorobutyrate Cu 2(PFB) 4(THF) 2 (PFB = O 2CC 3F 7) is volatile and sublimes at 190 °C/2 × 10 −4 Torr. Difluoroacetate derivatives Cu 2(O 2CCHF 2) 4(THF) 2 and [Ba(O 2CCHF 2) 2] m have also been prepared. In addition to elemental analysis, FT-IR, 1H NMR or ESR spectroscopies, some adducts have also been characterized by single crystal X-ray diffraction. Cu 2(μ,η 2-PFB) 4(THF) 2 and Cu 2(μ,η 2-TFA) 4(η 1-OHC 2H 4O i Pr) 2 show the usual paddle-wheel structure of the dinuclear Cu(II) carboxylate adducts. The barium derivative with N-methyldiethanolamine is the first example of an ionic barium trifluoroacetate derivative, all trifluoroacetates acting as counter ion.

Rhodium (II) compounds with functionalized metalated phosphines as bridging ligands

The reaction of Rh 2(O 2CCH 3) 4 · 2CH 3OH with the phosphine P(4-BrC 6H 4) 2(C 6H 5), 2, results in the formation of the monometalated compound Rh 2(O 2CCH 3) 3[PC] · 2CH 3CO 2H (PC representing a metalated P(4-BrC 6H 4) 2(C 6H 5)). The reaction involves selective metalation of the phosphine at one Br-substituted ring (12:1 isomer ratio). The reaction of Rh 2(O 2CCH 3) 3[(4-BrC 6H 3)P(4-BrC 6H 4)(C 6H 5)] · 2CH 3CO 2H, 4, with one additional mol of triphenylphosphine yields a mixture of two main stereoisomers Rh 2(O 2CCH 3) 2[(4-BrC 6H 3)P(4-BrC 6H 4)(C 6H 5)] [(C 6H 4)P(C 6H 5) 2] · 2CH 3CO 2H, 5a and 5b, that were isolated as pure compounds. These two compounds were resolved in the corresponding M and P enantiomers as trifluoroacetate derivatives that show good enantioselectivities in catalytic transformation of α-diazocarbonyl compounds.

Chiral exo‐Alkylidenecyclopentanes from (1S,4R)‐7,7‐Dimethyl‐1‐vinylbicyclo[2.2.1]heptan‐2‐one.

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Electron ionization mass spectral fragmentation of derivatized 4,5- and 5,6-epoxysterols.

The electron ionization (EI) mass spectral fragmentation of derivatized 4,5- and 5,6-epoxysterols was investigated. Interesting fragmentation processes involving a transannular cleavage of the epoxide ring after transfer of the trimethylsilyl group are significant in the case of 4,5-epoxysterol trimethylsilyl ethers (affording abundant fragment ions at m/z 403 and 404). Different pathways, which have been substantiated by deuterium labelling, are proposed in order to explain the formation of these ions. In contrast, this transfer is not significant in the case of 5,6-epoxysterol trimethylsilyl ethers. The EI mass spectra of these latter compounds appear to be very complex and to differ slightly according to the stereochemistry of the epoxy group. Acetate and trifluoroacetate derivatives of 4,5-epoxysterols display interesting EI mass spectra dominated by a fragment ion at m/z 332 resulting from cleavage of the steroid ring A.

Two-, Three-, and Four-Coordinate Ag(I) Coordination Polymers Formed by the Novel Phosphinite PPh2(3-OCH2C5H4N)

The novel phosphinite PPh(2)(3-OCH(2)C(5)H(4)N) (1) has been synthesized, and its coordination properties to Ag(I) have been studied. When reacted in a 1:1 ratio with Ag(I), coordination polymers with different coordination numbers about the Ag are found depending on the anion. For PPh(2)(3-OCH(2)C(5)H(4)N)AgBF(4) (2), a two-coordinate Ag is observed with a P-Ag-N angle of 167 degrees. Mixed three and four coordination about Ag is observed for PPh(2)(3-OCH(2)C(5)H(4)N)AgOTf (3), and for the trifluoroacetate derivative, PPh(2)(3-OCH(2)C(5)H(4)N)Agtfa (4), only a four-coordinate Ag is produced. X-ray crystal-structure determinations for compounds 2-4 have been carried out. The X-ray structures show a wide range of Ag-Ag distances in the polymers, which are dependent on the conformation of the bridging ligand.

Chiral exo-Alkylidenecyclopentanes from (1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one

(1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one oxime in the system (CF3CO)2O-CF3COOH and (1S,4R)-1-(1,2-dibromoethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one in the system MeONa-MeOH undergo fragmentation to give exo-alkylidenecyclopentane derivatives, (4R)-4-cyanomethyl-5,5-dimethyl-1-[(1E)-trifluoroacetoxyethylidene]cyclopentane and isomeric (4R)-4-carboxymethyl-1-[(1ZE)-2-methoxyethylidene]-5,5-dimethylcyclopentanes, respectively. The trifluoroacetate derivative undergoes unusual rearrangement, yielding an equilibrium mixture of two isomers with endo- and exocyclic double bond.

ChemInform Abstract: Radical Deoxygenation of Alcohols via Their Trifluoroacetate Derivatives with Diphenylsilane.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Radical deoxygenation of alcohols via their trifluoroacetate derivatives with diphenylsilane

Trifluoroacetate derivatives of alcohols can be used as precursors for the radical deoxygenation of alcohols with diphenylsilane. The reaction afforded high isolated yields of the deoxygenated products and neutral reaction conditions.