Stereoselective synthesis of deuterated β-cyclohexenylserine, a biosynthetic intermediate of the salinosporamides

A straightforward, highly stereoselective protocol toward the synthesis of deuterium-labeled (2R,3S,4S)-β-cyclohexenylserine has been developed. Key steps are a Nozaki-Hiyama-Kishi reaction generating the stereogenic centers and a ring-closing metathesis for the construction of the cyclohexenyl ring system. The labeled amino acid was further activated as an SNAc-ester for feeding experiments.     

Synthesis and characterization of a novel Fe3O4@SiO2/bipyridinium dichloride nanocomposite and its application as a magnetic and recyclable phase-transfer catalyst in the preparation of β-azidoalcohols, β-cyanohydrins,and β-acetoxy alcohols

β-Azidoalcohols, β-cyanohydrins, and β-acetoxy alcohols have been synthesized in the presence of a Fe₃O₄@SiO₂/bipyridinium nanocomposite (Fe₃O₄@SiO₂/BNC) as a novel magnetic and recyclable phase-transfer catalyst (PTC) in water. The catalyst was characterized with FT–IR, SEM, XRD, VSM, and TGA. This methodology offers several advantages, including easy work-up procedure, excellent regioselectivity, high yields, short reaction times, recyclable catalyst, easy separation of the catalyst through an external magnet and eco-friendly procedure.     

Synthesis of phenols by the intramolecular condensation of β, β' ,δ ,δ'-tetraoxoalkanedioates a novel BF3 -promoted claisen condensation of

The aromatization process of β, β', δ , δ'-tetraoxoalkanedioates, which were synthesized by the BF₃-promoted Claisen condensation, was examined.     

Synthesis of pyridine derivatives by the three-component condensation of a β-dicarbonyl compound, β-enaminocarbonyl compound, and ethyl orthoformate

The major products of the three-component condensation of a -dicarbonyl compound, -enaminocarbonyl compound, and ethyl orthoformate are pyridine derivatives. The reaction of 1,3-cyclohexanedione or dimedone, the enamino ketones obtained from these diones, and ethyl orthoformate gives octahydroacridinediones, while the reaction of dimedone, ethyl -aminocrotonate, and ethyl orthoformate gives a tetrahydroquinoline derivative. The structures of the minor products were established in some cases. The reduction of 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydro-1,8-acridinedione by LiAlH₄ proceeds with retention of the pyridine ring and leads to the corresponding octahydroacridinediol.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 774–781, June, 1999.     

The design and synthesis of a novel organophosphorus compound containing the structure of both β-amino acid and β-aminophosphonate

<正>A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P(OEt)_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.     

Production of β-carotene from beet molasses by Blakeslea trispora in stirred-tank and bubble column reactors

The effect of aeration rate and agitation speed on β-carotene production from molasses by Blakeslea trispora in a stirred-tank fermentor and optimization of the production of the pigment in a bubble column reactor were investigated. In addition, a central composite design was employed to determine the maximum β-carotene concentration at optimum values for the process variables (aeration rate, sugar concentration, linoleic acid, kerosene). By image analysis of the morphology of the fungus, a quantitative characterization of the hyphae and zygospores formed was obtained. The hyphae were differentiated to intacthyphae, vacuolated hyphae, evacuated cells and degenerated hyphae. An increased proportion of zygospores was correlated to high β-carotene production. In the stirred-tank fermentor, the highest concentration of the carotenoid pigment (92.0 mg/L) was obtained at an aeration rate of 1.5 vvm and agitation speed of 60 rpm. In the bubble column reactor, the aeration rate and concentration of sugars, linoleic acid, kerosene, and antioxidant significantly affected the production of β-carotene. In all cases, the fit of the model was found to be good. Aeration rate, sugar concentration, linoleic acid, and kerosene had a strong positive linear effect on β-carotene concentration. Moreover, the concentration of the pigment was significantly influenced by the negative quadratic effects of the given variables and by their positive or negative interactions. Maximum β-carotene concentration (360.2 mg/L) was obtained in culture grown in molasses solution containing 5% (w/v) sugar supplemented with linoleic acid (37.59 g/L), kerosene (39.11 g/L), and antioxidant (1.0 g/L).     

Synthesis and study of the trypanocidal activity of catechol-containing 3-arylcoumarins,inclusion in β-cyclodextrin complexes and combination with benznidazole

American trypanosomiasis or Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and is considered a neglected disease, being an important problem for public health. Benznidazole (BZN) is the drug used to treat the disease. However, it has limited efficacy and adverse side effects. Therefore, the development of new therapeutic alternatives is necessary. In this work, the trypanocidal activity and cytotoxicity of a series of catechol-containing 3-arylcoumarins, their combination with BZN, and the inclusion in β-cyclodextrins (β-CDs), were evaluated. The results obtained showed that the entire series has moderate trypanocidal activity on the trypomastigote form of the parasite, being the 3-(4′-bromophenyl)-6,7-dihydroxycoumarin (8) the most active compound (IC₅₀ = 34 μM) and the most cytotoxic in Vero cells (IC₅₀ = 162 μM) as well. By forming the inclusion complex 8-β-CDs, the trypanocidal activity and cytotoxicity decreased. In addition, the formation of inclusion complexes increased the solubility. The possible mechanism of action of 8 was evaluated and proved to be through the generation of oxidative stress. The combination with BZN presented a synergistic effect on the trypanocidal activity, reducing the necessary dose of BZN. The presence of a catechol in the studied scaffold seems to modulate the trypanocidal activity, and the combination of drugs proved to be a promising alternative strategy for treating the disease.     

Use of bacterial cellulose in the textile industry and the wettability challenge—a review

Bacterial cellulose (BC) has been studied as an alternative material in several segments of the food, pharmaceutical, materials and textile industries. The importance of BC is linked to sustainability goals, since it is an easily degradable biomaterial of low toxicity to the environment and is a renewable raw material. For use in the textile area, bacterial cellulose has attracted great interest from researchers, but it presents some challenges notably to its hydrophilic structure. This integrative review article brings together studies and methods related to minimizing the hydrophilicity of bacterial cellulose, in order to expand its applicability in the textile industry in its dry state. The databases consulted were Scopus, ScienceDirect, ProQuest and Web of Science, the documents investigated were scientific articles and the time period investigated was between 2015 and 2021. The results showed that although there are methods to make the BC membrane more hydrophobic, future studies in this regard and on other properties must continue so that bacterial cellulose can be commercially introduced in the textile sector.

     

Development of a simplified method for the simultaneous determination of retinol, α-tocopherol,and β-carotene in serum by liquid chromatography–tandem mass spectrometry with atmospheric pressure chemical ionization

A new and simple method for the determination of fat-soluble vitamins (retinol, alpha-tocopherol, and beta-carotene) in human serum was developed and validated by using liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS-MS). Different solvent mixtures were tested to obtain deproteinization and extraction of the analytes from the matrix. As a result, a volume of 240 microL of a 1:1 (v/v) ethanol/ethyl acetate mixture added to 60 microL of serum was found to be suitable for both protein precipitation and antioxidants solubilization, giving the best recovery for all three analytes. Deproteinized samples (20 microL) were injected after dilution, without the need for concentration or evaporation to dryness and reconstruction of the sample. Vitamins were separated on a C-8 column using a 95:5 (v/v) methanol/dichloromethane mixture and ionized in the positive-ion mode; detection was performed in the selected-reaction monitoring mode. Linearity of the LC-APCI-MS-MS method was established over 5 orders of magnitude for retinol and alpha-tocopherol, whereas in the case of beta-carotene it was limited to 4 orders. Lower limits of quantitation were 1.7, 2.3, and 4.1 nM for retinol, alpha-tocopherol, and beta-carotene, respectively. Serum concentrations of retinol, alpha-tocopherol, and alpha+beta-carotene determined in a group of healthy volunteers were 2.48, 38.07, and 0.50 microM, respectively, in samples collected in winter ( n=122) and 2.69, 45.88, and 0.90 microM during summer ( n=66).     

Kinetic resolution of secondary alcohols by the combination of a chiral Brønsted acid, DABCO, and acetyl chloride

An efficient and simple protocol for the kinetic resolution of secondary alcohols is presented. The new system is based on a combination of chiral Br?nsted acid, DABCO, and acetyl chloride and gives various enantioenriched alcohols with selectivity factors up to 105.     

Assay of uranium in crude diuranate cakes and MgF2 slag produced at the natural uranium conversion plants by γ-ray spectrometry

A transmission-corrected -ray counting method has been employed for the assay of uranium in crude Na₂U₂O₇ cakes produced at the Uranium Conversion Facilities. A 3×3 NaI(TI) detector was used in conjunction with a 400-channel analyzer. The observed count rate of the 1 MeV -ray emitted by the²³⁸U in the sample was corrected for sample self-attenuation, measured with a⁶⁵Zn (-energy 1115 keV) transmission source. A calibration factor determined by measuring a standard of known amount of radioactive material in the same form and geometry as the unknown sample was used to convert the transmission corrected count rate to the amount of uranium in the weighted sample. Another -spectrometric method is described for the assay of the U-content in the MgF₂ slag produced during the magnesiothermic reduction of UF₄ to U-metal ingots at the natural U-conversion plant.     

In vivo and in vitro metabolism of a novel β2-adrenoceptor agonist, trantinterol: metabolites isolation and identification by LC-MS/MS and NMR

Trantinterol is a novel β₂-adrenoceptor agonist used for the treatment of asthma. The aim of this study is to identify the metabolites of trantinterol using liquid chromatography tandem mass spectrometry (LC-MS/MS), to isolate the main metabolites, and confirm their structures by nuclear magnetic resonance (NMR). Urine, feces, bile, and blood samples of rats were obtained and analyzed. Reference standards of six metabolites were achieved with the combination of chemical synthesis, microbial transformation, and the model systems of rats. Moreover, in order to investigate the phase I metabolism of trantinterol in humans and to study the species differences between rats and humans, incubations with liver microsomes were performed. The biotransformation by a microbial model Cunninghamella blakesleana AS 3.970 was also studied. A total of 18 metabolites were identified in vivo and in vitro together, 13 of which were newly detected. Three phase I metabolites were detected in vivo and in vitro as well as in the microbial model, including the arylhydroxylamine (M1), the tert-butyl hydroxylated trantinterol (M2) and the 1-carbonyltrantinterol (M3). Another important pathway in rats is glutathione conjugation and further catabolism and oxidation to form consecutive derivatives (M4 through M10). Other metabolites include glucuronide, glucoside, and sulfate conjugates. The results of in vitro experiments indicate no species difference exists among rats, humans, and C. blakesleana AS 3.970 on the phase I metabolism of trantinterol. Our study provided the most comprehensive picture for trantinterol in vivo and in vitro metabolism to this day, and may predict its metabolism in humans.     

Porpholactams and chlorolactams: replacement of a β,β'-double bond in meso-tetraphenyl-porphyrin and -chlorin by a lactam moiety

Reaction of meso-tetraphenylporpholactone with hydrazine converts the lactone moiety to an N-aminolactam. It also reduces the opposite pyrrolic moiety of both the starting material and the N-aminolactam, generating chlorin-like chlorolactone and N-aminochlorolactam, respectively. Reductive N-N cleavage of the N-aminoporpholactam generates the parent porpholactam.     

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza-Michael addition and subsequent ring closure

Novel β-aminocyclobutanecarboxylic acid derivatives were prepared via a sequential solvent-free aza-Michael addition of benzophenone imine across 3-halopropylidenemalonates and base-induced ring closure. These highly substituted cyclobutanedicarboxylic acid derivatives were subjected to a reactivity study which demonstrated the tendency of these donor-acceptor substituted four-membered rings to be converted into their corresponding ring-opened products.     

Synthesis and biological evaluation of potential new inhibitors of the bacterial transferase MraY with a β-ketophosphonate structure

Stable analogs of bacterial transferase MraY substrate or product with a pyrophosphate surrogate in their structure are described. β-ketophosphonates were designed as pyrophosphate bioisosteres and were investigated as UDP-GlcNAc mimics. The developed strategy allows introduction of structural diversity at a late stage of the synthesis. The biological activity of the synthesized compounds was evaluated on the MraY enzyme.     

Synthesis and characterization of a novel nanomagnetic phase-transfer catalyst and its application to regioselective synthesis of β-azido and β-nitro alcohols in water

Immobilization of polyethylene glycol-substituted 1-methylimidazolium bromide on the surface of magnetic Fe₃O₄ nanoparticles through hexane-1,6-diyldicarbamate linker afforded a powerful and reusable heterogeneous phase-transfer catalysis which was successfully used for regioselective ring opening of epoxides with azide and nitrite anions in aqueous medium. The new catalyst can readily be recovered by simple magnetic decantation and recycled several times without appreciable loss of catalytic activity.     

Structural study of the inclusion compounds of thymol, carvacrol and eugenol in β-cyclodextrin by X-ray crystallography

The crystal structures of the inclusion compounds of thymol, carvacrol and eugenol, (components of essential oils of vegetable origin) in β-cyclodextrin have been determined. Thymol/β-CD crystallizes in the space group P1 containing two host molecules in its asymmetric unit whereas both carvacrol/β-CD and eugenol/β-CD complexes crystallize in the space group C2. In all three complexes two host molecules form head-to-head dimers their guest/host stoichiometry being: 1/2 (carvacrol/β-CD), 2/2 (thymol/β-CD) and 3/2 (eugenol/β-CD). In the cases of the thymol/β-CD and the carvacrol/β-CD complexes the β-CD dimers are arranged according to the channel packing mode. The accommodation of the geometrical isomer guests is performed solely by their hydrophobic groups revealing the leading role of the hydrophobic driving forces in the complexation process whereas the position of their hydroxyl group affects the stoichiometry of the formed dimeric complexes. In the case of the eugenol/β-CD dimeric complex one guest molecule is found lying between the β-CD groups in a sandwich fashion whereas the other two symmetry related guests protrude outwards the narrower rim of the hosts with only their hydrophobic allyl-chain located inside the hosts’ cavities. This arrangement prohibits the formation of a channel and the observed crystal packing is that of a Tetrad mode.     

Kinetic study of growth,lipid and carotenoid formation in β-carotene producing <Emphasis Type="Italic">Rhodotorula glutinis</Emphasis>

The oleaginous and red yeast Rhodotorula glutinis CCY 20-2-26 is known for its high-storage lipids accumulation in cells as well as for β-carotene biosynthesis. The work is focused on the study of lipogenesis and carotenoid pigments formation by the yeast grown in media with four different C/N ratios (20:1, 50:1, 70:1 and 100:1). Total fatty acids accumulation in cells reached the maximal value of 48% and yielded up to 8.9 g fatty acid/L media under C/N 70:1. On contrary, while the highest pigment accumulation in the yeast (1268 μg/g of cells) was found at the C/N ratio of 20:1, the maximal carotenoid yield (mainly β-carotene) of 12.7 mg/L was obtained under 50:1 ratio. Calculation of kinetic parameters of metabolites production revealed the metabolic correlations among glucose consumption, lipogenesis and carotenoid biosynthesis. It was demonstrated that glucose exhaustion resulted in reduction of growth and lipid accumulation in cells. Then, storage fatty acids, especially palmitic and oleic acids, begun to be degraded by β-oxidations and formed acetyl-CoA which was especially used for biosynthesis of β-carotene. This is the first study providing the new hypothesis about the metabolic connection between fatty acids and β-carotene metabolism in the red yeasts.     

Structure elucidation of EI-1941-1 and -2, novel interleukin-1β converting enzyme inhibitors produced by Farrowia sp. E-1941

EI-1941-1 (1a) and EI-1941-2 (2a) accompanied by EI-1941-3 (3) have been isolated from culture broth of Farrowia sp. E-1941 as the inhibitors of interleukin-1β converting enzyme. The structures of 1a, 2a, and 3 were elucidated by the analysis of NMR and MS data, and finally the absolute stereochemistries of 1a and 2a were confirmed by optical rotation data, or X-ray crystallographic analysis of p-bromobenzoate, 2b, respectively.