Solvent effect in the chromatographic enantioseparation of 1,1′-bi-2-naphthol on a polysaccharide-based chiral stationary phase

Enantioseparation of 1,1′-bi-2-naphthol (BINOL) was performed on a polysaccharide-based chiral stationary phase, Chiralcel OD-H, under normal-phase mode. The effects of polar modifier in the mobile phase on the retention, enantioseparation and elution order were investigated in detail. Solvent-induced reversal of elution order for BINOL was observed. When linear alcohols were adopted, R-BINOL was always eluted first. S-BINOL was eluted first when 2-propanol was used as a polar modifier. Enantioseparation could not be obtained when sec-butyl alcohol or tert-butyl alcohol was used as a polar modifier. When isoamyl alcohol or cyclohexanol was used as a polar modifier, favorable enantioseparation was obtained as with 1-pentanol or 1-hexanol; also, R-BINOL was the first-eluted enantiomer. It is worth emphasizing that significantly better enantioseparation was obtained when higher alcohols were used as polar modifier of the mobile phase. A nonlinear characteristic for the ln α against 1/T plots was universally observed in this study though the ln k against 1/T plots exhibited a linear feature. Associated with the obtained thermodynamic parameters, some interesting inferences about chiral recognition mechanism were proposed.     

Diastereoselective synthesis of β-aminosulfones from the 1,2-addition to N-(para-methoxyphenyl) imines

The base-promoted 1,2-addition of alkyl phenylsulfones to N-(para-methoxyphenyl) imines was investigated as a direct route to stereochemically defined β-aminosulfones. Using ⁿBuLi as base, 2-(phenylsulfonyl)ethylbenzene was added to a range of N-(para-methoxyphenyl) imines to give β-aminosulfone products in high yields as single anti-diastereoisomers. Other less substituted alkyl phenylsulfones were not as successful.     

Kinetic resolution of vic-amino alcohols catalyzed by a chiral Cu(II) complex

Kinetic resolution of N-benzoylated vic-amino alcohols was achieved by benzoylation in the presence of copper triflate and (R,R)-Ph-BOX as catalysts. The observed enantioselectivity was moderate to high. The method was applied to a kinetic resolution of racemic prolinol and piperidinemethanol derivatives as well as an asymmetric desymmetrization of 2-amino-1,3-diol derivatives.     

Effect of ring fusion stereochemistry on double bond geometry. Unexpected formation of nine-membered cyclic ether with E-configurated double bond through RCM

Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating.     

Synthesis of cis-3,4-diaryl α-methylene-γ-butyrolactams via sonochemical Barbier-type reaction

A series of cis-3,4-diaryl α-methylene-γ-butyrolactams were synthesized by the addition reaction of 3-phenylallyl bromide with N-tosyl aldimine via sonochemical Barbier-type reaction condition and then followed by the in situ intramolecular amidation. The cis-3,4-diaryl α-methylene-γ-butyrolactam was obtained as the sole regio- and stereoisomeric product when N-tosyl aldimine was used as the substrate whereas the monoaryl α-methylene-γ-butyrolactam was also generated when N-phenyl aldimine was used.     

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature

Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.     

Stereoselective hydrolysis of sec-mono-alkyl sulfate esters with retention of configuration

An optimised method for the stereoselective hydrolysis of sec-alkylsulfate monoesters with absolute retention of configuration was developed. Under optimised conditions, clean hydrolysis of (R)-2-octyl sulfate was achieved in aqueous t-butyl methyl ether (3:97) using 0.6 equiv of p-toluenesulfonic acid as catalyst and 0.33 equiv of dioxane as mediator to give (R)-2-octanol as the sole product in the absence of side reactions, such as racemisation or elimination.     

Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase

3-O-α-d-Glucopyranosyl-swainsonine was originally proposed¹⁷ as a potential inhibitor of the mammalian enzyme endo-α-mannosidase, but its synthesis has not been reported. Herein we report the total synthesis of this enigmatic compound, utilizing a halide-ion catalysed glycosylation of a swainsonine lactam with a glucosyl iodide donor as the key step. The resulting inhibitor was evaluated as an inhibitor of human endo-α-mannosidase, and as a ligand for bacterial orthologs from Bacteroides thetaiotaomicron and Bacteroides xylanisolvens, including active-centre variants, although no evidence for binding or inhibition was observed. The surprising lack of binding was rationalized by using structural alignment with an endo-α-mannosidase inhibitor complex, which identified deleterious interactions with the swainsonine piperidine ring and an essential active site residue.     

Macrocystis pyrifera Extract Residual as Nutrient Source for the Production of Sophorolipids Compounds by Marine Yeast Rhodotorula rubra

Seaweed processing generates liquid fraction residual that could be used as a low-cost nutrient source for microbial production of metabolites. The Rhodotorula strain is able to produce antimicrobial compounds known as sophorolipids. Our aim was to evaluate sophorolipid production, with antibacterial activity, by marine Rhodotorula rubra using liquid fraction residual (LFR) from the brown seaweed Macrocystis pyrifera as the nutrient source. LFR having a composition of 32% w/w carbohydrate, 1% w/w lipids, 15% w/w protein and 52% w/w ash. The best culture condition for sophorolipid production was LFR 40% v/v, without yeast extract, artificial seawater 80% v/v at 15 °C by 3 growth days, with the antibacterial activity of 24.4 ± 3.1 % on Escherichia coli and 21.1 ± 3.8 % on Staphylococcus aureus. It was possible to identify mono-acetylated acidic and methyl ester acidic sophorolipid. These compounds possess potential as pathogen controllers for application in the food industry.     

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH₃CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.     

Viscosity of heavy n-alkanes and diffusion of gases therein based on molecular dynamics simulations and empirical correlations

The viscosity of pure n-alkanes and n-alkane mixtures was studied by molecular dynamics (MD) simulations using the Green–Kubo method. n-Alkane molecules were modeled based on the Transferable Potential for Phase Equilibria (TraPPE) united atom force field. MD simulations at constant number of molecules or particles, volume and temperature (NVT) were performed for n-C₈ up to n-C₉₆ at different temperatures as well as for binary and six-component n-alkane mixtures which are considered as prototypes for the hydrocarbon wax produced during the Gas-To-Liquid (GTL) Fischer–Tropsch process. For the pure n-alkanes, good agreement between our simulated viscosities and existing experimental data was observed. In the case of the n-alkane mixtures, the composition dependence of viscosity was examined. The simulated viscosity results were compared with literature empirical correlations. Moreover, a new macroscopic empirical correlation for the calculation of self-diffusion coefficients of hydrogen, carbon monoxide, and water in n-alkanes and mixtures of n-alkanes was developed by combining viscosity and self-diffusion coefficient values in n-alkanes. The correlation was compared with the simulation data and an average absolute deviation (AAD) of 11.3% for pure n-alkanes and 14.3% for n-alkane mixtures was obtained.     

Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.     

Volatiles and Antifungal-Antibacterial-Antiviral Activity of South African Salvia spp. Essential Oils Cultivated in Uniform Conditions

Spontaneous emissions of S. dentata Aiton and S. scabra Thunb., as well as the essential oil (EO) composition of the cited species, together with S. aurea L., were investigated. The chemical profile of the first two species is reported here for the first time. Moreover, in vitro tests were performed to evaluate the antifungal activity of these EOs on Trichophyton mentagrophytes, Microsporum canis, Aspergillus flavus, Aspergillus niger, and Fusarium solani. Secondly, the EO antibacterial activity against Escherichia coli, Staphylococcus aureus, and Staphylococcus pseudointermedius was examined, and their antiviral efficacy against the H1N1 influenza virus was assessed. Leaf volatile organic compounds (VOCs), as well as the EOs obtained from the arial part of Salvia scabra, were characterized by a high percentage of sesquiterpene hydrocarbons (97.8% and 76.6%, respectively), mostly represented by an equal amount of germacrene D (32.8% and 32.7%, respectively). Both leaf and flower spontaneous emissions of S. dentata, as well as the EO composition, showed a prevalence of monoterpenes divided into a more or less equal amount of hydrocarbon and oxygenated compounds. Interestingly, its EO had a non-negligible percentage of oxygenated sesquiterpenes (29.5%). S. aurea EO, on the contrary, was rich in sesquiterpenes, both hydrocarbons and oxygenated compounds (41.5% and 33.5%, respectively). S. dentata EO showed good efficacy (Minimal Inhibitory Concentration (MIC): 0.5%) against M. canis. The tested EOs were not active against E. coli and S. aureus, whereas a low inhibition of S. dentata EO was observed on S. pseudointermedius (MIC = 10%). Once again, S. dentata EO showed a very good H1N1 inhibition; contrariwise, S. aurea EO was completely inactive against this virus. The low quantity of S. scabra EO made it impossible to test its biological activity. S. dentata EO exhibited interesting new perspectives for medicinal and industrial uses.     

Selective and facile synthesis of α,β-unsaturated nitriles and amides with N-hydroxyphthalimide as the nitrogen source

The direct conversion of α,β-unsaturated aldehydes to corresponding nitriles promoted by Pd(OAc)₂ and phthalic acid which was hydrolyzed from N-hydroxyphthalimide (NHPI) has been disclosed. Additionally, it was found that when water was used as the solvent, α,β-unsaturated amides was obtained as the main products in good to excellent yields. It was first reported that NHPI was utilized as the nitrogen source to synthesize α,β-unsaturated nitriles and amides from aldehydes. Control experiment demonstrated that aldehydes undergo a process of oximation and dehydration to form nitriles and amides.     

Low-fluorinated homopolymer from heterogeneous ATRP of 2,2,2-trifluoroethyl methacrylate mediated by copper complex with nitrogen-based ligand

We report the preparation of low-fluorinated homopolymer via heterogeneous atom transfer radical polymerization (ATRP) of 2,2,2-trifluoroethyl methacrylate (TFEMA) using 2,2′-bipyridine (bpy), N,N,N′,N′,N″-pentamethyldiethylenetriamine (PMDETA), and tris(2-(dimethylamino)ethyl)amine (Me₆TREN) as representatives for di-, tri-, and tetradentate amine ligands, respectively. The ATRP was better controlled, yielding polymers with controlled molecular weights and low polydispersities (M_w/M_n ca. 1.11) when bpy was used as a ligand than when PMDETA was used. This was further supported by the results of our kinetic and chain extension studies. However, the ATRP of TFEMA had lower monomer conversions and gel formation when Me₆TREN was used as the ligand. Further reported are the thermal-properties, as well as the surface properties of the films from the resulting polymers with different molecular weights.     

Peagol and peagoldione, two new strigolactone-like metabolites isolated from pea root exudates

Two new strigolactone-like metabolites, named peagol and peagoldione, with germinative activity for root parasitic plants, were isolated from pea root exudates and were characterized by spectroscopic methods. Peagol was more active on Orobanche foetida and Phelipanche aegyptiaca seeds, while peagoldione was active on P. aegyptiaca only. Low activity was found on Orobanche crenata and Orobanche minor. Stimulatory activity of peagol on O. foetida seeds is most relevant as this species does not respond to the synthetic strigolactone analogue GR24, usually used as Orobanche germination standard.     

Chemical synthesis of RNA via 2′-O-cyanoethylated intermediates

It was found that 2′-O-cyanoethyl group could be removed from 2′-O-cyanoethylated ribonucleoside derivatives by treatment with Bu₄NF. This finding was successfully applied to the synthesis of oligoribonucleotides via their 2′-O-cyanoethylated derivatives as key intermediates where a cyanoethyl group was used as the 2′-hydroxyl protecting group. The rate of condensation using this protecting group in the presence of various activators was generally faster than that observed when a TBDMS group was used as the protecting group.     

Synthesis of (E)-2-(1-ferrocenylmethylidene)malonic acid derivatives by a cobalt-catalyzed domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines

The domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines was investigated in the presence of Co₂(CO)₈ as catalyst. In most cases the main products are 2-(1-ferrocenylmethylidene) malonates formed by an N(1)-C(4) cleavage of the primarily derived β-lactams. The latter compounds could only be isolated when the reaction was carried out at relatively low CO pressure, using an excess of ethyl diazoacetate. trans-N-(tert-Butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam proved to be the most stable one among these compounds and could be isolated in 55% yield. N-alkyl β-lactams were shown to undergo acidic cleavage leading to the E isomers of 2-(1-ferrocenylmethylidene) malonates as the main products. The structures of the two new compounds, (E)-2-ethoxycarbonyl-3-ferrocenyl-N-((R)-1-phenylethyl)-2-propenamide and trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam were confirmed by X-ray crystallography. The relative thermodynamical stability of the products as well as the energetics of the acid-mediated cleavage of the β-lactam ring was elucidated with DFT calculations.     

SXI route to mesostructured materials from Fau and Beta zeolite precursors: A comparative study of their assembly behaviors in extremely acidic media

Mesoporous molecular sieves were synthesized from Beta and Fau zeolite precursors through S⁺X⁻I⁺ route under extremely acidic conditions in parallel (designated as M_Beta and M_Fau, respectively). The textural properties of M_Fau were different from its M_Beta counterpart but resembled normal MCM-41 silica from TEOS. Al content in M_Beta was almost equivalent to that in the initial Beta zeolite precursors, whereas only trace Al species was present in M_Fau from elemental analysis results. The hydrothermal stability of M_Beta after post-synthesis ammonia treatment was considerably improved compared with normal MCM-41 aluminosilicates, whereas the M_Fau after the same procedure was as unstable as normal MCM-41 silica. Thus, the assembly behaviors of Beta and Fau zeolite precursors were comparatively studied based on these results. The microstructure of Fau zeolite precursors were degraded by the extremely acidic condition, and Al species was dissolved into the synthesis mixture. However, Beta zeolite precursors survived the chemical attack of extremely acidic media and were incorporated into mesostructured framework as primary building units.