Lipase-catalyzed synthesis of medium- and long-chain diesters of 2-oxoglutaric acid

Abstract

The influence of various reaction parameters, such as alcohol-to-substrate ratio, enzyme-to-substrate ratio, solvent and temperature, on the enzymatic preparation of a series of novel medium- and long-chain esters of 2-oxoglutaric acid has been evaluated. Among the tested lipases, those from Candida antarctica and Carica papaya appeared to be the best catalysts. Mild reaction conditions and low environmental impact make the biocatalytic procedure a convenient way to prepare the reported products, which are potential fat substitutes in the food industry.     

Reaction of Astaxanthin with Peroxynitrite

The in vitro reactivities of astaxanthin toward peroxynitrite were investigated and the reaction products after scavenging with peroxynitrite were analyzed in order to determine the complete mechanism of this reaction. A series of carotenoids, 13-apo-astaxanthinone (1), 12′-apo-15′-nitroastaxanthinal (2), 12′-apo-astaxanthinal (3), 10′-apo-astaxanthinal (4), 9-cis-14′-s-cis-15′-nitroastaxanthin (5), 14′-s-cis-15′-nitroastaxanthin (6), 13-cis-14′-s-cis-15′-nitroastaxanthin (7), 10′-s-cis-11′-cis-11′-nitroastaxanthin (8), 13,15,13′-tri-cis-15′-nitroastaxanthin (9), 9-cis-astaxanthin (10), and 13-cis-astaxanthin (11), were isolated from the reaction products of carotenoids with peroxynitrite. Our previous studies achieved for the first time the isolation of nitro derivatives from the reaction of astaxanthin with peroxynitrite. Here we identify the major remaining reaction products of this reaction and investigate the stabilities of the nitro astaxanthins.     

Oxoiron(IV) porphyrin π-cation radical complexes with a chameleon behavior in cytochrome P450 model reactions

There is an intriguing, current controversy on the involvement of multiple oxidizing species in oxygen transfer reactions by cytochromes P450 and iron porphyrin complexes. The primary evidence for the multiple oxidants theory was that products and/or product distributions obtained in the catalytic oxygenations were different depending on reaction conditions such as catalysts, oxidants, and solvents. In the present work, we carried out detailed mechanistic studies on competitive olefin epoxidation, alkane hydroxylation, and C=C epoxidation versus allylic C–H hydroxylation in olefin oxygenation with in situ generated oxoiron(IV) porphyrin -cation radicals (1) under various reaction conditions. We found that the products and product distributions were markedly different depending on the reaction conditions. For example, 1 bearing different axial ligands showed different product selectivities in competitive epoxidations of cis-olefins and trans-olefins and of styrene and para-substituted styrenes. The hydroxylation of ethylbenzene by 1 afforded different products, such as 1-phenylethanol and ethylbenzoquinone, depending on the axial ligands of 1 and substrates. Moreover, the regioselectivity of C=C epoxidation versus C–H hydroxylation in the oxygenation of cyclohexene by 1 changed dramatically depending on the reaction temperatures, the electronic nature of the iron porphyrins, and substrates. These results demonstrate that 1 can exhibit diverse reactivity patterns under different reaction conditions, leading us to propose that the different products and/or product distributions observed in the catalytic oxygenation reactions by iron porphyrin models might not arise from the involvement of multiple oxidizing species but from 1 under different circumstances. This study provides strong evidence that 1 can behave like a chameleon oxidant that changes its reactivity and selectivity under the influence of environmental changes.Electronic Supplementary Material Supplementary material is available for this article at .     

Nucleophilic Substitution Reactions of 5-Bromo-6-methyluridines

Abstract

The reactions of the 5-bromo-6-methyl-2′,3′-O-isopropylideneuridines 9 and 10 with a number of nucleophiles in hot DMF have been investigated. With acetate ion as the nucleophile, either the 5-acetoxy- (11,12) or the 6-acetoxymethyl- (15) products can be obtained in modest yield depending upon the exact reaction conditions. With nitrogen nucleophiles (aniline or p-methoxybenzylamine) reaction takes place at the 6-methyl carbon, whereas with sulfur nucleophiles (thiophenol, thioacetate) only the 5-substituted products are obtained.     

SYNTHESIS AND BIOLOGICAL EVALUATION OF S-GLYCOSYLATED PYRIDINES

ABSTRACT

The formation of thioglycosides 7a-j and 10a-j via the reaction of sodium salts of thiopyridines 3a-e with glycosyl bromides 6a,b has been studied. Comparison with the products obtained from silylated thiopyridines 8a-e and peracetylated sugars 9a,b is made. ¹³C NMR was utilized to elucidate the proposed structures of the products.     

Damage to photosystem II by lipid peroxidation products

BackgroundPhotosystem II proteins of higher plant chloroplasts are prone to oxidative stress, and most prominently the reaction center-binding D1 protein is damaged under abiotic stress. The reactive oxygen species produced under these stress conditions have been suggested to be responsible for the protein injury.Scope of reviewRecently, it has been shown that the primary and secondary products of non-enzymatic and enzymatic lipid peroxidation have a capability to modify photosystem II proteins. Here, we give an overview showing how lipid peroxidation products formed under light stress and heat stress in the thylakoid membranes cause oxidative modification of proteins in higher plant photosystem II.Major conclusionsDamage to photosystem II proteins by lipid peroxidation products represents a new mechanism underlying photoinhibition and heat inactivation.General significanceComplete characterization of photosystem II protein damage is of crucial importance because avoidance of the damage makes plants to survive under various abiotic stresses. Further physiological significance of photosystem II protein oxidation by lipid peroxidation product should have a potential relevance to plant acclimation because the oxidized proteins might serve as signaling molecules.     

Synthesis of novel sulfonamide analogs containing sulfamerazine/sulfaguanidine and their biological activities

Sulfamerazine and sulfaguanidine are clenched with p-nitrobenzoyl chloride and the products obtained are reduced to Na_xS in ethanol–water. Novel sulfonamides (6a–g and 9a–g) were synthesized by the reaction of these reduced products (4 and 8) with various sulfonyl chlorides (5a–g). The structures of these compounds were characterized using spectroscopic analysis (IR, ¹H-NMR, ¹³C-NMR and HRMS) technique. Antimicrobial activity of sulfonamides (3, 4, 7, 8, 6a–g and 9a–g) was evaluated by the agar diffusion method. These compounds showed antimicrobial activity against tested microorganism strains (Gram-positive bacteria, clinic isolate and yeast and mold). Compounds 9d, 9e, 9a, 6d and 6e showed particularly antimicrobial activity against tested Gram-positive (Bacillus cereus and B. subtilis) and Gram-negative (Enterobacter aerogenes) bacteria.     

REACTION OF N3-BENZOYL-3′,5′-O-(DI-TERT-BUTYLSILANEDIYL)URIDINE WITH HINDERED ELECTROPHILES: INTERMOLECULAR N3 To 2′-O PROTECTING GROUP TRANSFER

ABSTRACT

The compound N³-benzoyl-3′,5′-O-(di-tert-butylsilanediyl)uridine 2 was alkylated with various alkyl iodides in CH₃CN in the presence of base. Normal 2′-O-alkylated products were obtained with methyl or benzyl iodide. if hindered alkyl iodides with β-branching such as 2-ethylbutyl iodide were used as electrophiles under the same conditions, N³-alkyl-2′-O-benzoyl uridine derivatives were produced. This unexpected transformation is usually dormant with reactive alkylating agents, but expressed with sterically hindered, less reactive electrophiles. This unwanted reaction gives isomeric products whose spectra differ in only subtle ways from target compounds.     

Formation Mechanism of the Free Radical Product and Its Precursor by the Reaction of Dehydro-L-ascorbic Acid with Amino Acid

During the formation of radical A (2) and its precursor (tris(2-deoxy-2-L-ascorbyl)amine, 1) by the reaction of dehydroascorbic acid (DHA) with amino acid, ascorbic acid (AsA) and the reduced red pigment (3) were newly identified, in addition to scorbamic acid (SCA) and the red pigment (4), as intermediate products. The addition of AsA to the DHA-amino acid reaction, as well as to the DHA-SCA reaction, greatly increased the formation of 3 and 1. The reaction of AsA with 4 gave rapidly 3, followed by the gradual production of 1. From these results, a reaction pathway is proposed that 3 formed by the reduction of 4 with AsA is a key intermediate and its condensation with DHA followed by reduction with AsA might produce 2 and 1.     

Discovery and biochemical characterization of a mannose phosphorylase catalyzing the synthesis of novel β-1,3-mannosides

BackgroundMannoside phosphorylases are frequently found in bacteria and play an important role in carbohydrate processing. These enzymes catalyze the reversible conversion of β-1,2- or β-1,4-mannosides to mannose and mannose-1-phosphate in the presence of inorganic phosphate.MethodsThe biochemical parameters of this recombinantly expressed novel mannose phosphorylase were obtained. Furthermore purified reaction products were subjected to ESI- and MALDI-TOF mass spectrometry and detailed NMR analysis to verify this novel type of β-1,3-mannose linkage.ResultsWe describe the first example of a phosphorylase specifically targeting β-1,3-mannoside linkages. In addition to mannose, this phosphorylase originating from the bacterium Zobellia galactanivorans could add β-1,3-linked mannose to various other monosaccharides and anomerically modified 5-bromo-4-chloro-3-indolyl-glycosides (X-sugars).ConclusionsAn unique bacterial phosphorylase specifically targeting β-1,3-mannoside linkages was discovered.General significanceFunctional extension of glycoside hydrolase family 130.     

Asymmetric microbial reduction of ethyl and isoprophyl α,1,3-trioxo-2-isoindolinebutyrate

Summary Microorganisms are capable of the asymmetric reduction of various types of ketones. From a limited screening with 103 selected microbial strains two have been chosen which reduce ethyl and isopropyl ,1,3-trioxo-2-isoindolinebutyrate (1a and 1b) stereoselectively. The optically active products ethyl and isopropyl -hydroxy-1,3-dioxo-2-isoindoline butyrate (2a and 2b) are useful precursors of the cerebral insufficiency improver hydroxy-aniracetam. Up to 3% of substrates 1a or 1b can be added in the reaction medium and converted by Candida parapsilosis. The isolated (R)-enantiomers of the product alcohols 2a and 2b show an enantiomeric excess (ee) of 98%–99%. The process was successfully tested on a 200-1 scale, the transformation rate being 0.83 g/1 per day and the yield of isolated product 72%. With Torulopsis magnoliae (S)-enantiomers of the products 2a and 2b were formed with an ee of 97%–99%.Offprint requests to: Hans G. W. Leuenberger     

Reaction of Retinol with Peroxynitrite

The reactivity of retinol with peroxynitrite, which is a strong oxidant and has been reported to induce several biological damages, was investigated. 13-cis-14-nitroretinol (1), 13-trans-14-nitroretinol (2), 13-apo-β-carotenone (3), retinal (4), 11,14-epoxyretinol (5), and 11,15-epoxyretinol (6) were identified as reaction products of retinol with peroxynitrite. From these results, it was observed that retinol can undergo a nitration reaction with peroxynitrite. Furthermore, the formation mechanisms of 1, 2, and 3 from retinol with peroxynitrite are discussed.     

Oxetanocin—Oxetanose Chemistry: Lewis Acid Promoted Glycosidations of the D-Erythrooxetanose Derivatives

Abstract

Upon treatment of 1-O-acetyl-D-erythrooxetanoses (17a,b and 26) with trimethylsilyl N-benzoyladenine or allyltrimethylsilane in the presence of SnCl₄, the ring expanded products (18, 19 and 29) or the acyclic compounds (27 and 28) were obtained. The reaction mechanism involving a novel ring opening process is discussed.     

The reaction force and the transition region of a reaction

The reaction force F(R) and the position-dependent reaction force constant κF(R) are defined by F(R)=-∂V(R)/∂R and κ(R)=∂²V(R)/∂R², where V(R) is the potential energy of a reacting system along a coordinate R. The minima and maxima of F(R) provide a natural division of the process into several regions. Those in which F(R) is increasing are where the most dramatic changes in electronic properties take place, and where the system goes from activated reactants (at the force minimum) to activated products (at the force maximum). κ(R) is negative throughout such a region. We summarize evidence supporting the idea that a reaction should be viewed as going through a transition region rather than through a single point transition state. A similar conclusion has come out of transition state spectroscopy. We describe this region as a chemically-active, or electronically-intensive, stage of the reaction, while the ones that precede and follow it are structurally-intensive. Finally, we briefly address the time dependence of the reaction force and the reaction force constant.     

Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid

The reaction of trioxane and tetraoxane endoperoxides with unsaturated phospholipid 1 in the presence of Fe(II) was investigated in the absence of oxygen by means of tandem ESI-MS analysis. The spectral analyses for the reaction mixtures showed that artemisinin 2 with a trioxane structure gave no peak except that for the remaining intact phospholipid 1 (m/z 758.9), indicating that there was no structural change to 1. On other hand, the reaction mixture of 1 with tetraoxanes 3 and 4 afforded a number of new peaks (m/z 620–850) that were presumably assigned to oxidative degradation products originating from phospholipid 1. Since this reaction was completely inhibited by the addition of a phenolic antioxidant, the process was considered to involve some free radical species. The newly discovered marked differences in reactivity between the trioxane and the tetraoxanes possibly reflects their different anti-malarial mechanisms, and this reactivity may contribute to the classification of a number of anti-malarial endoperoxides whose mode of action is based on phospholipid oxidation.     

Photodimerizations of hydroxy- and benzoylated 4-azachalcones and quantum chemical investigation of the reactions

Photodimerization reactions of compounds 4–6 gave four new cyclobutane-containing compounds (7–9) with full control over the stereochemistry at the four stereogenic centers. These new cyclobutane-containing compounds had β-truxinic (7a), δ-truxinic (7b and 9), and ε-truxillic (8) structures. However, o-, m-, and p-hydroxy 4-azachalcones (1–3) did not give photochemical cyclization products under any conditions (in solvent or in their solid or molten states). Experimental data suggested the possibility of frontier orbital control over stereochemical behavior, so some theoretical calculations were performed. Full geometrical optimization of compounds 1–9 was performed via DFT B3LYP/6-31⁺G**, and their electronic structures were also investigated. The geometries of the singlet and triplet states were initially optimized by density functional theory (DFT) and the configuration interaction singles (CIS) B3LYP/3-21⁺G** level. An additional calculation was performed for the triplet state using the ground-state geometry. The possible photochemical dimerization products of compounds 7–9 (a–g) and the intrinsic reaction coordinates (IRCs) of the reactions of compounds 4–6 were calculated theoretically by the DFT/3-21⁺G** method. The configurations (reactant, transition state, product, and reaction pathway) corresponding to the stationary points (minima or saddle points) were determined. The intrinsic reaction coordinates were followed to verify the energy profiles that connect each TS to the appropriate local minimum. The dimeric products expected from the calculations coincided with the dimers produced experimentally.     

The Synthesis of 5-Substituted-2, 4-dimethoxypyrimidines and Some Related Nucleoside Analogues

Abstract

The reaction of 5-formyl-2,4-dimethoxypyrimidine with active methylene compounds in the Knoevenagel reaction and the subsequent nucleoside formation reactions of some of the products was investigated. A new synthesis of (E)-5-(2-bromovinyl)uracil and an improved synthesis of 5-formyl-2′,3′-isopropylidene uridine are reported.     

Revisit to the Reaction of O-Phenylene Diamine with Thiosemicarbazide to Give Benzimidazole-2-Thione Rather than Benzotriazine-2-Thione and its Glycosylation

Reaction of o-phenylene diamine with thiosemicarbazide did not give benzotriazine-2-thione 2 as reported, although the product was found to be benzimidazole-2-thione 3. Glycosylation of 3 with acetobromo sugars 4a-4b gave the respective thioglycosides 7a-7d in addition to minor products of the nucleosides 8a and 8b, in the case of the gluco- and galacto-analogs, respectively. The regioselectivity of glycosylation reaction has been investigated.     

Natural products are an important source for proteasome regulating agents

BackgroundNatural medicines have a long history in the prevention and treatment of various diseases in East Asian region, especially in China. Modern research has proved that the pharmacological effects of numerous natural medicines involve the participation of ubiquitin proteasome system (UPS). UPS can degrade the unwanted and damaged proteins widely distributed in the nucleus and cytoplasm of various eukaryotes.PurposeThe objective of the present study was to review and discuss the regulatory effects of natural products and extracts on proteasome components, which may help to find new proteasome regulators for drug development and clinical applications.MethodsThe related information was compiled using the major scientific databases, such as CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Wiley Online, and GeenMedical. The keywords “natural product” and “proteasome” were applied to extract the literature. Nature derived extracts, compounds and their derivatives involved in proteasome regulation were included, and the publications related to synthetic proteasome agents were excluded.ResultsThe pharmacological effects of more than 80 natural products and extracts derived from phytomedicines related to the proteasome regulation were reviewed. These natural products were classified according to their chemical properties. We also summarized some laws of action of natural products as proteasome regulators in the treatment of diseases, and listed the action characteristics of the typical natural products.ConclusionNatural products derived from nature can induce the degradation of damaged proteins through UPS or act as regulators to directly regulate the activity of proteasome. But few proteasome modulators are applied clinically. Summary of known rules for proteasome modulators will contribute to discover, modify and synthesize more proteasome modulators for clinical applications.     

Synthesis of Novel Olefinic Carbocyclic Purine Nucleoside Analogues

Abstract

The synthesis of optically pure unsaturated carbocyclic nucleoside analogues is described. (3,4S)-Bis(t-butyldiphenyl silyloxymethyl)-1R and 1S cyclopent-2-en-1-ol were coupled with 6-chloropurine and 2-amino-6-chloropurine respectively, using a modified Mitsunobu reaction. The products were reacted further using standard procedures to give compounds 12, 14, 16 and 18.