Search Results (146)

The reaction of either the L (2S3R) or D (2R3S) enantiomers of H₂N-C*H(R)CO₂⁻ (R = -C*H(OH)CH₃ or -C*H(OH)CH(CH₃)₂) and the L (2S) or D (2R) enantiomers of H₂N-C*H(C(CH3)₂OH)CO₂⁻ with imidazole-4-carboxaldehyde and nickel(II) acetate in methanol yields a single stereoisomer of an oxazolidine. There is retention of chirality on ring positions 4 and 5 (if C_β is chiral) of the oxazolidine, C_α and C_β of the parent amino acid, and transfer of chirality to the newly generated stereogenic centers, ring positions 3, the amino acid nitrogen atom, N_AA, and 2, the aldehyde carbon atom, C_ald. Specifically, when C_α has an S configuration, both N_AA and C_ald are formed as R. Likewise, a C_α which is R results in both N_AA and C_ald being formed as S. For example, the reaction of L threonine (C_α is S and C_β is R) with 4-imidazolecarboxaldehyde in the presence of nickel(II) gives the facial Λ NiL₂, where L is (2R, 3R, 4S, 5R) 4-carboxylato-5-methyl-2-(4-imidazolyl)-1,3-oxazolidine. The same reaction with D threonine produces the enantiomeric Δ complex of (2S, 3S, 4R, 5S) 4-carboxylato-5-methyl-2-(4-imidazoyl)-1,3-oxazolidine. The high stereospecificity is thought to be based on the fused three-ring structure of the characterized nickel complexes in which the hydrogen atoms of C_α, N_AA, and C_ald must be cis to one another. Identical reactions occur with 2-pyridine carboxaldehyde and LT or DT. In contrast, the reactions of L allo threonine (2S3S) and the primary alcohols, L or D serine, give the conventional meridionally coordinated aldimine product. Full article

Ustiloxins are a group of cyclopeptide mycotoxins produced by rice false smut pathogen Villosiclava virens (anamorph: Ustilaginoidea virens) which seriously threaten the safety production of rice and the health of humans and livestock. Ustiloxin A, accounting for 60% of the total ustiloxins, is the main toxic component. Biotransformation, a process of modifying the functional groups of compounds by means of regio- or stereo-specific reactions catalyzed by the enzymes produced by organisms, has been considered as an efficient way to detoxify mycotoxins. In this study, the endophytic fungus Petriella setifera Nitaf10 was found to be able to detoxify ustiloxin A through biotransformation. Two transformed products were obtained by using the cell-free extract (CFE) containing intracellular enzymes of P. setifera Nitaf10. They were structurally characterized as novel ustiloxin analogs named ustiloxins A1 (1) and A2 (2) by analysis of the 1D and 2D NMR and HRESIMS spectra as well as by comparison with known ustiloxins. The cytotoxic activity of ustiloxins A1 (1) and A2 (2) was much weaker than that of ustiloxin A. The biotransformation of ustiloxin A was found to proceed via oxidative deamination and decarboxylation and was possibly catalyzed by the intracellular amine oxidase and oxidative decarboxylase in the CFE. An appropriate bioconversion was achieved by incubating ustiloxin A with the CFE prepared in 0.5 mol/L phosphate buffer (pH 7.0) for 24 to 48 h. The optimum initial pH values for the bioconversion of ustiloxin A were 7–9. Among eight metal ions (Co²⁺, Cu²⁺, Fe³⁺, Zn²⁺, Ba²⁺, Ca²⁺, Mg²⁺ and Mn²⁺) tested at 5 mmol/L, Cu²⁺, Fe³⁺ and Zn²⁺ totally inhibited the conversion of ustiloxin A. In conclusion, detoxification of ustiloxin A through oxidative deamination and decarboxylation is an efficient strategy. Full article

Amino acid analogues with a phosphorus-containing moiety replacing the carboxylic group are promising sources of biologically active compounds. The H-phosphinic group, with hydrogen–phosphorus–carbon (H-P-C) bonds and a flattened tetrahedral configuration, is a bioisostere of the carboxylic group. Consequently, amino-H-phosphinic acids undergo substrate-like enzymatic transformations, leading to new biologically active metabolites. Previous studies employing NMR-based metabolomic and proteomic analyses show that in Escherichia coli, α-KG-γ-P_H (the distal H-phosphinic analogue of α-ketoglutarate) can be converted into L-Glu-γ-P_H. Notably, α-KG-γ-P_H and L-Glu-γ-P_H are antibacterial compounds, but their intracellular targets only partially overlap. L-Glu-γ-P_H is known to be a substrate of aspartate transaminase and glutamate decarboxylase, but its substrate properties with NAD⁺-dependent glutamate dehydrogenase (GDH) have never been investigated. Compounds containing P-H bonds are strong reducing agents; therefore, enzymatic NAD⁺-dependent oxidation is not self-evident. Herein, we demonstrate that L-Glu-γ-P_H is a substrate of eukaryotic GDH and that the pH optimum of L-Glu-γ-P_H NAD⁺-dependent oxidative deamination is shifted to a slightly alkaline pH range compared to L-glutamate. By ³¹P NMR, we observe that α-KG-γ-P_H exists in a pH-dependent equilibrium of keto and germinal diol forms. Furthermore, the stereospecific enzymatic synthesis of α-KG-γ-P_H from L-Glu-γ-P_H using GDH is a possible route for its bio-based synthesis. Full article

In this work, an attempt is made to theoretically substantiate the experimentally known facts of the influence of halogen concentration on the catalytic properties of the neodymium-based Ziegler–Natta system. Based on the structural and thermochemical data obtained using modern methods of quantum chemistry, the process of the 1,3-butadiene cis-1,4-polymerization under the model active centers of the neodymium Ziegler–Natta catalysts with different contents of chloride ions was studied. Results are presented that explain the increase in the cis-stereospecificity and activity of the polymerization system with an increase in the content of the chloride ions in the neodymium catalytic system. Reasons were established for the decrease in the concentration of active centers relative to the introduced Nd(III) with an excess of chloride ions and the occurrence of the anti-syn isomerization as a source of the formation of the trans-1,4-structures in the cis-1,4-polybutadiene. Full article

Some syndiotactic-rich polyolefins, generally difficult to synthesize through stereospecific polymerization of the corresponding monomers, were prepared by homogeneous non-catalytic hydrogenation of syndiotactic 1,2 poly(1,3-diene)s with diimide, arising from thermal decomposition of p-toluene-sulfonyl-hydrazide. All the polymers synthesized were structurally characterized by means of several analytical techniques, such as FT-IR, NMR (¹H, ¹³C and 2D), DSC, and GPC, and herein illustrated. Full article

A novel and concise synthetic method for arenastatin A, a cytotoxic cyclic depsipeptide of marine origin, was developed in this study. The convergent assembly of the four segments, including the cross-metathesis reaction, gave a cyclization precursor, and Fmoc deprotection caused simultaneous macrocyclization. The Corey–Chaykovsky reaction using a chiral sulfur ylide afforded arenastatin A with complete stereoselectivity in the longest linear sequence of seven reaction steps from the known compound. Using this synthetic method, some analogs of segment B were prepared through a late-stage diversification strategy. The simple S_N2 reaction of the thiolate toward the tosylate precursor, prepared using almost the same synthetic method as described above, provided the desired sulfide analogs. Full article

Derived from the denitrifying bacterium Aromatoleum aromaticum EbN1 (Azoarcus sp.), the enzyme S-1-(4-hydroxyphenyl)-ethanol dehydrogenase (S-HPED) belongs to the short-chain dehydrogenase/reductase family. Using research techniques like UV-Vis spectroscopy, dynamic light scattering, thermal-shift assay and HPLC, we investigated the catalytic and structural stability of S-HPED over a wide temperature range and within the pH range of 5.5 to 9.0 under storage and reaction conditions. The relationship between aggregation and inactivation of the enzyme in various pH environments was also examined and interpreted. At pH 9.0, where the enzyme exhibited no aggregation, we characterized thermally induced enzyme inactivation. Through isothermal and multitemperature analysis of inactivation data, we identified and confirmed the first-order inactivation mechanism under these pH conditions and determined the kinetic parameters of the inactivation process. Additionally, we report the positive impact of glucose as an enzyme stabilizer, which slows down the dynamics of S-HPED inactivation over a wide range of pH and temperature and limits enzyme aggregation. Besides characterizing the stability of S-HPED, the enzyme’s catalytic activity and high stereospecificity for 10 prochiral carbonyl compounds were positively verified, thus expanding the spectrum of substrates reduced by S-HPED. Our research contributes to advancing knowledge about the biocatalytic potential of this catalyst. Full article

The unique prolyl isomerase Pin1 binds to and catalyzes cis–trans conformational changes of specific Ser/Thr-Pro motifs after phosphorylation, thereby playing a pivotal role in regulating the structure and function of its protein substrates. In particular, Pin1 activity regulates the affinity of a substrate for E3 ubiquitin ligases, thereby modulating the turnover of a subset of proteins and coordinating their activities after phosphorylation in both physiological and disease states. In this review, we highlight recent advancements in Pin1-regulated ubiquitination in the context of cancer and neurodegenerative disease. Specifically, Pin1 promotes cancer progression by increasing the stabilities of numerous oncoproteins and decreasing the stabilities of many tumor suppressors. Meanwhile, Pin1 plays a critical role in different neurodegenerative disorders via the regulation of protein turnover. Finally, we propose a novel therapeutic approach wherein the ubiquitin–proteasome system can be leveraged for therapy by targeting pathogenic intracellular targets for TRIM21-dependent degradation using stereospecific antibodies. Full article

The homogeneous non-catalytic hydrogenation of several types of iso- and syndiotactic cis-1,4 poly(1,3-diene)s with diimide, formed by thermal decomposition of p-toluene-sulfonyl-hydrazide, was examined. Perfectly alternating ethylene/1-alkene copolymers having different tacticity (i.e., isotactic and syndiotactic), which in some cases are difficult to synthesize by simple stereospecific co-polymerization of the corresponding monomers, were obtained. All the copolymers synthesized were fully characterized from a structural, morphological, and rheological point of view through different analytical techniques (FT-IR, NMR, GPC, DSC, RX). Full article

A convenient protocol for the synthesis of 25,26,27-tribenzoyl-28-[((S)-1-diphenylphos- phanyl-propan-2-yl)oxy]-calix[4]arene via stereospecific methylation on Evans’ oxazolidinone moiety was reported. According to the ¹³C NMR analysis of this phosphine, the calix[4]arene skeleton adopted a 1,3-alternate conformation. The latter conformation of the macrocycle and the (S)-chirality of the carbon atom bearing the methyl substituent were confirmed by a single-crystal X-ray diffraction study. After coordination of the phosphinated ligand to the dimeric [RuCl₂(p-cymene)]₂ organometallic precursor, the resulting arene–ruthenium complex was tested in the asymmetric reduction of acetophenone and alcohol was obtained with modest enantiomeric excess. Full article

Two approaches to the synthesis of para-menthene epoxide ((1S,5S,6R)-4) are developed. The first approach includes a reaction between chlorohydrin 7 and NaH in THF. The second involves the formation of epoxide in the reaction of corresponding diacetate 6 with sodium tert-butoxide. One possible mechanism of this reaction is proposed to explain unexpected outcomes in the regio- and stereospecificity of epoxide (1S,5S,6R)-4 formation. The epoxide ring in (1S,5S,6R)-4 is then opened by various S- and O-nucleophiles. This series of reactions allows for the stereoselective synthesis of diverse derivatives of the monoterpenoid Prottremine 1, a compound known for its antiparkinsonian activity, including promising antiparkinsonian properties. Full article

Structured lipids (SLs) offer a promising avenue for designing novel formulations enriched in n-3 long-chain polyunsaturated fatty acids (LCPUFAs) with potential health benefits. Triacylglycerols (TAGs), the most common fats in the human diet, are both non-toxic and chemically stable. The metabolic efficiency and digestibility of TAGs are significantly influenced by the position of fatty acids (FAs) within the glycerol backbone, with FAs at the sn-2 position being readily absorbed. Over the past two decades, advancements in SL research have led to the development of modified TAGs, achieved either through chemical or enzymatic processes, resulting in SLs. The ideal structure of SLs involves medium-chain FAs at the sn-1,3 positions and long-chain n-3 LCPUFAs at the sn-2 position of the glycerol backbone, conferring specific physicochemical and nutritional attributes. These tailored SL formulations find wide-ranging applications in the food and nutraceutical industries, showing promise for dietary support in promoting health and mitigating various diseases. In particular, SLs can be harnessed as functional oils to augment TAG metabolism, thereby impeding the development of fatty liver, countering the onset of obesity, and preventing atherosclerosis and age-related chronic diseases. In scrutinising prevailing research trajectories, this review endeavours to provide an in-depth analysis of the multifaceted advantages and repercussions associated with the synthesis of SLs. It elucidates their burgeoning potential in enhancing health and well-being across a range of demographic cohorts. Specifically, the implications of SL utilisation are discussed in the context of healthcare environments and early childhood developmental support. Full article

Syndiotactic polystyrene (SPS) refers to a type of thermoplastic material with phenyl substituents that are alternately chirally attached on both sides of an aliphatic macromolecular main chain. Owing to its excellent physical and mechanical properties, as well as its chemical stability, high transparency, and electrical insulation characteristics, SPS is used in a wide variety of technical fields. SPS is commonly produced via the stereoselective transition metal-catalyzed coordination polymerization method mediated by stereospecific catalysts, which consists of anionic mono-cyclopentadienyl derivative η⁵-coordinated single active metal centers (referred to as “mono-Cp’-M”), with active center metals involving Group 4 transition metals (with an emphasis on titanium) and rare-earth (RE) metals of the periodic table. In this context, the use of mono-cyclopentadienyl titanocene (mono-Cp’Ti) catalysts and mono-cyclopentadienyl rare-earth metal (mono-Cp’RE) metallocene catalysts for the syndiospecific polymerization of styrene is discussed. The effects of the mono-cyclopentadienyl ligand structure, cationic active metal types, and cocatalysts on the activity and syndiospecificity of mono-Cp’ metallocene catalysts are briefly surveyed. Full article

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(R)-AD-1, 20(R)-AD-2, 20(S)-AD-1 and 20(S)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(R)-AD-1 and 20(R)-AD-2 was significantly better than 20(S)-AD-1 and 20(S)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(R)-AD-1 and 20(R)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(S)-AD-1 and 20(S)-AD-2 barely exhibited the same results. The results indicated that 20(R)-AD-1 and 20(R)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(R)-AD-1 and 20(R)-AD-2 as potential agents for human gastric carcinoma therapy. Full article

The lipoxygenase (LOX) cascade is a source of bioactive oxylipins that play a regulatory role in plants, animals, and fungi. Soybean (Glycine max (L.) Merr.) LOXs are the classical models for LOX research. Progress in genomics has uncovered a large diversity of GmLOX isoenzymes. Most of them await biochemical investigations. The catalytic properties of recombinant soybean LOX2 (GmLOX2) are described in the present work. The GmLOX2 gene has been cloned before, but only for nucleotide sequencing, while the recombinant protein was not prepared and studied. In the present work, the recombinant GmLOX2 behavior towards linoleic, α-linolenic, eicosatetraenoic (20:4), eicosapentaenoic (20:5), and hexadecatrienoic (16:3) acids was examined. Linoleic acid was a preferred substrate. Oxidation of linoleic acid afforded 94% optically pure (13S)-hydroperoxide and 6% racemic 9-hydroperoxide. GmLOX2 was less active on other substrates but possessed an even higher degree of regio- and stereospecificity. For example, it converted α-linolenic acid into (13S)-hydroperoxide at about 98% yield. GmLOX2 showed similar specificity towards other substrates, producing (15S)-hydroperoxides (with 20:4 and 20:5) or (11S)-hydroperoxide (with 16:3). Thus, the obtained data demonstrate that soybean GmLOX2 is a specific (13S)-LOX. Overall, the catalytic properties of GmLOX2 are quite similar to those of GmLOX1, but pH is optimum. Full article