Synthesis and Biological Activity of Triacetonamine

Sterically hindered amines such as triacetonamine and certain closely related analogs have been applied in medicine, pharmacology and industry. Various methods of synthesis of 2,2,6,6-tetramethylpiperidin-4-one (triacetonamine) derivatives start generally with acetone, phorone, piperidine N-oxides, piperidine alcohols, and 4-dimethylamine piperidine derivatives. Physical properties of triacetonamine including density, boiling point, flash point, and melting point have been determined. Reactions of triacetonamine derivatives with various organic reagents are also summarized. Triacetonamine derivatives react via three functional groups including carbonyl, methylenes adjacent to the carbonyl group, and NH. Some other miscellaneous reactions are presented. Conformation of triacetonamine is described. Theoretical models for the conformations of triacetonamine have been developed by quantum and molecular mechanics methods. Triacetonamine demonstrates different types of biological activities, such as antialzheimer, antifungal, antimicrobial, anti-HIV, anticancer, antioxidant, P38 kinase inhibitor, DNA labelling, antispasmodic, and psychotropic, and high ganglionic blocking.     

Effect of Alkali Treatment of HY Zeolite on Continuous Synthesis of Triacetonamine

The continuous synthesis of triacetonamine from acetone and ammonia over HY was realized. Meanwhile, alkali‐treated HY with different structure and acidities were prepared and examined. The results indicated that the acid sites, especially Brønsted acid sites, played a vital role on the selectivity of triacetonamine and the conversion of acetone. It was further confirmed by X‐ray diffraction (XRD), N₂ adsorption and desorption experiments, IR spectra of adsorbed pyridine, and NH₃ temperature‐programmed desorption. Meanwhile, the generation mechanisms of triacetonamine and impurities were speculated.     

Prediction of the crystal structure of a cyclic tetrapeptide

Prediction of the known crystal structure of cyclic-L-Ser(O-t-Bu)-β-Ala-Gly-L-β-Asp(OMe) has been attempted by establishing the low-energy conformations of the isolated molecule by conformational analysis, and then regarding each of these as a rigid molecule, by establishing the favorable crystal packing arrangements by molecular packing analysis. The theoretical model closest to the observed structure was one of the lowest-energy solutions and was recognized as essentially correct by reference to the x-ray data. The limitations of the model follow from the fact that the side chain conformations are somewhat affected by packing interactions.     

Theoretical studies of conjugated systems containing CC and CN fragments and their alkyl and amino derivatives

Ab initio molecular orbital theory has been systematically employed to investigate the structures, energies, and conformations of 27 nitrogen-containing compounds. A force field has been developed, on the basis of available experimental and theoretical data, to permit extension of the molecular orbital-based molecular mechanics calculations to hetero-conjugated systems. Structures, heats of formation, and conformations of more than 65 molecules were studied by the developed force field and the results were compared with the available experimental data.     

Duplex formation and the onset of helicity in poly d(CG)n oligonucleotides in a solvent-free environment

The gas-phase conformations of a series of cytosine/guanine DNA duplexes were examined by ion mobility and molecular dynamics methods. Deprotonated duplex ions were formed by electrospray ionization, and their collision cross sections measured in helium were compared to calculated cross sections of theoretical models generated by molecular dynamics. The 4-mer (dCGCG) and 6-mer (dCGCGCG) duplexes were found to have globular conformations. Globular and helical structures were observed for the 8-mer (dCGCGCGCG) duplex, with the globular form being the more favored conformer. For the 10-mer (dCGCGCGCGCG), 14-mer (dCGCGCGCGCGCGCG), and 18-mer (dCGCGCGCGCGCGCGCGCG) duplexes, only helical structures were observed in the ion mobility measurements. Theory predicts that the helical structures are less stable than the globular forms in the gas phase and should collapse into the globular form given enough time. However, molecular dynamics simulations at 300 K indicate the helical structures are stable in aqueous solution and will retain their conformations for a limited time in the gas phase. The presence of helical structures in the ion mobility experiments indicates that the duplexes retain "solution structures" in the gas phase on the millisecond time scale.     

Study of potassium O,O'-Dibutyldithiophosphate combining DFT, 31P CP/MAS NMR and infrared spectroscopy

Dithiophosphates are used in many different industrial applications. To explain their functions and properties in these applications, a fundamental understanding on a molecular level is needed. Potassium O, O'-Dibutyldithiophosphate and its anion have been investigated by means of a combination of DFT and (31)P CP/MAS NMR and infrared spectroscopy. Several low-energy conformations were studied by DFT. Three different conformations with significantly different torsion angles of the O-C bond relative to the O-P-O plane were selected for further studies of infrared frequencies and (31)P NMR chemical-shift tensors. A good agreement between theoretical and experimental results was obtained, especially when the IR spectra or (31)P chemical shift tensor parameters of all three conformations were added, indicating that, because of the low energy difference between the conformations, the molecules are rapidly fluctuating between them.     

Simulation of conformational changes occurring when a protein interacts with its receptor

In order to simulate the conformational changes occurring when a protein interacts with its receptor, we firstly evaluated the structural differences between the experimental unbound and bound conformations for selected proteins and created theoretical complexes by replacing, in each experimental complex, the protein-bound with the protein-unbound chain. The theoretical models were then subjected to additional modeling refinements to improve the side chain geometry. Comparing the theoretical and experimental complexes in term of structural and energetic factors is resulted that the refined theoretical complexes became more similar to the experimental ones. We applied the same procedure within an homology modeling experiment, using as templates the experimental structures of human interleukin-1beta (IL-1beta) unbound and bound with its receptor, to build models of the homologous proteins from mouse and trout in unbound and bound conformations and to simulate the interaction with the related receptors. Our results suggest that homology modeling techniques are sensitive to differences between bound and unbound conformations, and that modeling with accuracy the side chains in the complex improves the interaction and molecular recognition. Moreover, our refinement procedure could be used in protein-protein interaction studies and, also, applied in conjunction with rigid-body docking when is not available the protein-bound conformation.     

Diastereomer assignment of an olefin-linked bis-paracyclophane by ion mobility mass spectrometry

trans-1,2-Bis([2.2]paracyclophanyl)ethene (1) exists as a pair of diastereomers whose conformations, and thus effective collision cross sections, are quite different. The two forms can be obtained by different transition metal-catalyzed reactions. To assign meso and racemic structures, a novel method is reported in which experimental gas-phase ion mobility data are compared with theoretical structures obtained from molecular mechanics calculations.     

On the interpretation of residual dipolar couplings as reporters of molecular dynamics

The analysis of residual dipolar couplings from an ensemble of conformations to extract molecular dynamics is intricate. The very mechanism that is necessary to perturb overall molecular tumbling to generate nonvanishing residual dipolar couplings gives rise to convoluted data. The measured values are essentially weighted averages over conformations. However, the weights are not simply the populations of conformations. Consequently, the observed order parameter is not exactly the true measure of motion. In the case of paramagnetic alignment, the apparent order parameter is expected to depend on the number of torsions that separate the locus of interest from the paramagnetic site. In the case of alignment due to steric obstruction, the uneven selection of conformations by their differing Saupe order matrices leads to a bias in the residual dipolar couplings-probed molecular dynamics.     

Quantum theory of the structure and bonding in proteins : Part 14. The serine dipeptide

The energies of the conformations of the serine dipeptide are computed by ab initio molecular orbital theory in order to demonstrate the existence of the hydrogen bonds, torsion barriers and non-bonded repulsions which govern the relative energies of these conformations. The Ramachandran map of the dipeptide is computed and found to resemble closely those of alanine and ethyl glycine. The side-chain maps are them computed and analysed to show the above physical effects in terms of the torsion barrier-free maps.

There is generally good agreement between the experimental and theoretical results in the sense that all three side-chain conformations which are staggered about CC^β (₁ = + 60, 180 and −60°) are computed to be close in energy and all three values of ₁ occur with similar frequencies in the proteins examined. The fact that serine, unlike all other comparable residues except threonine, tends to favour a ₁ value of + 60° in the bridge region is reproduced clearly by the computations and analysis of the physical factors involved shows that this conformation is stabilised by side chain to backbone hydrogen bonding.     

Molecular complexes of IQ and 4-hydroxy-coumarin: a mutagen-anti-mutagen system

Molecular complexes formed between a cooked food mutagen-carcinogen (2-amino-3-methylimidazo[4,5-f] quinoline, IQ) and a potent anti-mutagen (4-hydroxy-coumarin, 4HC) were synthesized and crystallized from a solution. The active functional groups in IQ and in 4HC that may involve in the formation of these complexes are investigated by UV-visible, infrared, and NMR spectroscopy. The geometrical conformations and heat of formation of IQ:4HC complexes were optimized by semi-empirical molecular orbital calculations. The experimental and theoretical results indicate that the complexes exist in multiple conformations. The energetically favorable ones are formed via hydrogen-bonding type of interactions between amino group in IQ and carbonyl group in 4HC, and also between quinoline-nitrogen (and imidazole-nitrogen) in IQ and hydroxyl group in 4HC. The observed complex formation could serve as a model for understanding the active molecular sites responsible for the initial mutagenic activity in cooked-food mutagens as well as the anti-mutagenic activity in coumarins.     

Molecular recognition in cyclodextrin complexes of amino acid derivatives: the effects of kinetic energy on the molecular recognition of a pseudopeptide in a nonconstraining host environment as revealed by a temperature-dependent crystallographic study

The crystal structure of a triclinic 2:2 inclusion complex of beta-cyclodextrin with N-acetyl-L-phenylalanine methyl ester has been determined at several temperatures between 298 and 20 K to further study molecular recognition using solid-state supramolecular beta-cyclodextrin complexes. The study reveals kinetic energy dependent changes in guest molecule conformations, orientations, and positions in the binding pocket presented by the crystal lattice. Accompanying these changes are observable differences in guest-guest interactions and hydrogen-bonding interactions in the binding pocket that involve guest molecules, water of hydration molecules, and beta-cyclodextrin molecules. On the basis of the differences observed in the crystal structures, we present a solid-state example of a system that displays the properties of both classical and quantum chemical models. At higher temperatures, the structure conforms to a classical mechanical model with dynamic disorder. At lower temperatures, the observations conform to examples in which there is static disorder representative of models in which quantum states differing in conformation, position, and orientation of components in the crystal structure are occupied. Ab initio theoretical calculations on the different guest molecule conformations have been carried out. Superpositions of theoretical electrostatic surface potential diagrams on the observed molecular positions in the complexes provide confidence that the deconvolution of the guest molecule disorder is acceptable. Temperature-dependent solid-state magic angle spinning deuteron NMR measurements provide evidence for large-amplitude, diffusive motion on a microsecond time scale in the complex.     

Influence of highly polyunsaturated lipid acyl chains of biomembranes on the NMR order parameters

We investigate the effect of specific conformations of double-bond segments in highly polyunsaturated acyl chains on the deuterium (2)H NMR order parameters of a fully hydrated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC, 18:0/22:6 PC) lipid bilayer. The system is analyzed by performing a molecular dynamics simulation study at ambient conditions in the fluid lamellar phase. By separately calculating the different partial contributions to the total order parameter profiles measurable experimentally, we are able to get insights into the molecular origin of earlier experimental and theoretical observations. The effect of the position of the different conformations of double-bond segments along the polyunsaturated acyl chain is also examined. As in experiments performed in a series of lipid bilayers with an increasing number of cis double bonds per lipid molecule [Holte, L. L., et al. Biophys. J. 1995, 68, 2396], we find that unsaturations influence mainly the order of the bottom half of the saturated chain. Specific conformations of the polyunsaturated chain close to the lipid headgroups have a distinct effect on the order of the bottom half of the saturated chain and on the top half of the polyunsaturated chain. Our results indicate that for SDPC the conformation of the region of the polyunsaturated chain located between the first three cis double bonds is responsible for the major effects on the orientational order of both the saturated and the polyunsaturated chains.     

Synthesis of 2,2,6,6-tetramethylquinuclidine

A method was developed for the synthesis of the first representative of the previously unreported quinuclidine derivatives with four geminal substituents in the -positions with respect to nitrogen, viz., 2,2,6,6-tetramethylquinuclidine, from triacetonamine. Two variants were studied for building up the chain from two CH₂ links in the -position of triacetonamine using the Reformatskii and Knoevenagel reactions.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–234, February, 1971.     

Development of Molecular Mechanics Torsion Parameters for alpha,beta-Cyclopropyl Ketones and Conformational Analysis of Bicyclo[m.1.0]alkan-2-ones

Conformations of cyclopropyl methyl ketone have been studied using ab initio methods in an effort to quantify the effects of conjugative overlap between the cyclopropane ring and an adjacent ketone carbonyl. Results were comparable with previous experimental and theoretical studies. Cyclopropyl methyl ketone exhibits a global energy minimum in the s-cis conformer and a local energy minimum near the s-trans conformer. The potential energy curve obtained was used to derive torsion parameters which were employed in molecular mechanics studies of the conformations of the set of bicyclo[m.1.0]alkan-2-ones having larger ring sizes from five- to 16-membered. Similar conformations for the cyclopropyl ketone substructure are observed for all the medium and large ring systems examined. Possible synthetic ramifications of local conformational anchoring by this functional group array are discussed.     

新型手性酪氨酸修饰的锌卟啉对氨基酸酯的分子识别研究

合成并表征了一种L型Boc酪氨酸修饰的自由卟啉(L-BocTyrTAPP)及其锌卟啉配合物Zn(L-BocTyr)TAPP.通过紫外-可见光谱滴定法,研究了手性锌卟啉配合物与四对对映异构的手性氨基酸酯客体在CHCl₃中的分子识别行为.实验结果表明,在分子识别的过程中,缔合常数顺序均为D型略大于L型,且按K(PheOMe)>K(AIaOMe)>K(ValOMe)>K(LeuOMe)的顺序依次减小.同时,利用园二色光谱进一步阐述手性分子识别过程.此外,采用分子力学方法搜索了主客体体系的最低能量构象,从理论上对实验本质进行较深入的探讨.     

Electrochemical Synthesis of 3-Methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine

Electrochemical halogenation of 4-oxo-2,2,6,6-tetramethylpiperidine (triacetonamine) in the electrolytes triacetonamine-KX-CH₃ONa (X = Cl, Br, I) was studied, and a procedure was developed for preparing 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine by this reaction.     

中国海洋天然产物合成研究新进展

海洋天然产物合成研究是海洋天然有机化学最活跃的研究领域之一。本文综述中国海洋天然产物合成研究的最新进展,包括海洋环肽、西松烷(烯)和西松烷型二萜内酯、喹啉酮衍生物和三丙酮胺以及柳珊瑚酸类似物等。     

Preparative synthesis of 2,2,6,6-tetramethyl-4-oxopiperidin-1-oxyl

Summary When triacetonamine was slowly oxidized with an aqueous solution of hydrogen peroxide in the presence of sodium tungstate at room temperature, 2,2,6,6-tetramethyl-4-oxopiperidin-1-oxyl was obtained in good yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12 p. 2218, December, 1964     

Conformations of banana-shaped molecules studied by 2H NMR spectroscopy in liquid crystalline solvents

ClPbis11BB and Pbis11BB, two banana-shaped mesogens differing by a chlorine substituent on the central phenyl ring, show a nematic and a B2 phase, respectively. To obtain information on the structural features responsible for their different mesomorphic behavior, a study of the preferred conformations of these mesogens has been performed by NMR spectroscopy in two nematic media (Phase IV and ZLI1167), which should mimic the environment of the molecules in their own mesophases, avoiding problems of sample alignment by a magnetic field. To this aim, 2H NMR experiments have been performed on selectively deuterated isotopomers of ClPbis11BB and Pbis11BB and of two parent molecules, ClPbisB and PbisB, assumed as models in previous theoretical and experimental conformational studies. We found that only a limited number of conformations is compatible with experimental data, often very different from those inferred from theoretical calculations in vacuo, indicating a strong influence of the liquid crystalline environment on molecular conformation. No significant differences between chlorinated and non-chlorinated molecules were found, this suggesting that chlorine does not change the molecular conformational equilibrium, as previously proposed.