An Economical Large Scale Preparation of (2S,3S)-4,5-Dimethyl-2-Phenyl-L,3-Dioxolan

An economical 5-step synthesis of (2s,5s)-4,5-dimethyl-2-phenyl-l,3-dioxolan from (2R,3R)-tartaric acid is described.     

Experimental, Theoretical and Biological Activity Study on the Acyl-Substituted Benzo-18-crown-6, Dibenzo-18-crown-6 and Dibenzo-24-crown-8

Hexadecanoyl, dihexadecanoyl, dioctadecaneoyl, di-10-undecenoyl, and dicis-9-octadecenoyl derivatives of benzo[18]crown-6, dibenzo[18]crown-6 and dibenzo[24]-8 were synthesized by the condensation of carboxylic acids (palmitic, stearic, oleic and undecenoic acid) with benzo and dibenzo crown ethers in the presence of zinc chloride. The extraction equilibrium constants of such macrocyclic ethers with long side chains were estimated using chloroform/water and dichloromethane/water membranes transfer of Na-PAR (4-(2-pyridylazo)-resorcinol mono sodium monohydrate) with UV–Vis spectroscopy. It was found that they were in the range of 10.88–11.71 in dichloromethane and 8.04–11.77 in chloroform. These results actually show that the Na+ binding effect of macrocyclic ethers depends on the type and the length of side chains. The geometrical properties of the molecules were studied employing semi-empirical calculations by simulated annealing technique. The frontier molecular orbital energies and dipole moments were also examined. The biological activity results showed that the synthesized crown ethers have no activity against the studied microorganisms.     

Alkali Metal- and Ammonium Picrate Extraction and Complex Forming Capabilities of d-Glucose and d-Mannose-based Lariat Ethers

The alkali metal- and ammonium picrate extracting ability of d-glucose- and d-mannose-based 15-crown-5 ethers and related lariat ethers was investigated in dichloromethane – water system. A heteroatom was waried in the crown ether containing a 4,6-O-benzylidene-α-d-glucopyranoside unit 6, (X=O), 2 (X=S) and 8a (X=NH). Extracting ability of the latter species (8a) was excellent (97–99%) in regard of all cations (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺ and NH₄⁺) examined, it was not, howewer, selective. Introduction of a side arm on the nitrogen atom of 8a decreased the extracting ability, but increased the selectivity. In this series of compounds (8b–f, 4), 4 with a pyridylethyl substituent allowed the extraction of sodium picrate in 72%. The glucose-based macrocycles 8a, 8e and 8f formed a stronger complex with the cations examined than the mannose-based analogues 9a, 9e and 9f, that can be explained by the all-gauche conformation of the former ones. It was pointed out that in the case of crowns with tertiary amine moieties, the basicity increases the quantity of the picrates extracted. According to complex forming measurements by FAB-MS, the best sodium ion selectivity was achieved by the γ-hydroxypropyl substituted lariat ether (8e). Possible structures of the complexes formed by the two types of monosacharides with sodium cation were evaluated by molecule modelling calculations.     

Synthesis of 18pi annulenic fluorofullerenes from tertiary carbanions: size matters!

A range of tertiary carbanions XCH(CO2Et)2 of differing sizes have been reacted with C60F18 to assess the steric effect of X on the position of nucleophilic substitution. For X = CO2Et, NO2, P(O)(OMe)2, SO2CH2Ph, the all trans annulenes (trannulenes) were obtained as a result of extended S(N)2' (i.e. S(N)2') substitution; in the case of the phosphorus compound, with reduced amounts of base (DBU) dephosphonylation of one or more P(O)(OMe)2 groups by hydrogen occurred. Trannulene formation did not occur for X = F, CN due to the smaller size of the nucleophile, and in the latter case substitution was shown to take place by an S(N)2' mechanism, resulting in the addend being adjacent to a fluorine addend. Trannulenes (X = CO2Et, Br, Cl) exhibited reversible one-electron reductions at potentials (-0.02 to -0.09 V) significantly more positive than for [60]fullerene. Trannulene (X = NO2) exhibited an irreversible one-electron reduction (0.08 V); the irreversibility may be associated with fluorine loss. Conformational isomerism at temperatures below 298 K was observed for all trannulene derivatives as a result of eclipsing addend-addend interactions. Minimum energy conformations with a rotational energy barrier of 12-15 kcal mol(-1) were observed when these interactions are calculated using molecular mechanics.     

Gas-liquid chromatography of submicrogram amounts of drugs. V. Preparation of low-activity packed columns and their application to the toxicological analysis of underivatized polar drugs in the low nanogram range.

When diatomaceous earth and glass columns are acylated prior to coating with a silicone liquid phase, then subjected to heat treatment in an atmosphere of nitrogen, gas chromatographic columns can be prepared that show a marked reduction in adsorption. These columns can be used with a nitrogen-specific detector to chromatograph unmodified polar compounds such as morphine and cyclobarbital in nanogram amounts. Virtually no alteration of peak shape and no variation of retention time are observed over the range 10(-6)-10(-9) g of polar drugs. This represents, for these polar drugs, an "improvement" in chromatographic capability of the order of about 1000-fold in comparison with the best conventional commercial columns. Application to toxicological analysis of morphine in urine is described.     

In vitro photodynamic eradication of Pseudomonas aeruginosa in planktonic and biofilm culture

Photodynamic disinfection (PDD) is a nonantibiotic approach to treating drug-resistant bacterial infections. Pseudomonas aeruginosa , an opportunistic pathogen, is problematic because of its propensity to develop antibiotic resistance and its ability to secrete a protective biofilm matrix. This study examined the ability of PDD to eradicate planktonic and biofilm cultures of P. aeruginosa in vitro . Planktonic P. aeruginosa cultures were briefly exposed to a methylene blue-based photosensitizer formulation and subjected to energy doses ranging from 1.7 to 20.6 J cm⁻² using a 670 nm nonthermal diode laser. Biofilms were grown for 24 and 48 h and exposed to photosensitizer for 30 s before illumination with 13.2 or 26.4 J of energy. A single exposure of planktonic P. aeruginosa to photosensitizer at >15.5 J cm⁻² resulted in 100% eradication (>7 log₁₀ reduction from control), an effect that could be decreased significantly in the presence of the singlet oxygen quenchers l -tryptophan and sodium azide. Decreasing the energy dose below this threshold by varying both power density and illumination duration resulted in a dose-dependent decrease in bacterial kill. In addition, 24 h biofilm viability was reduced by 99% with single exposure and 99.9% with double exposure, while 48 h biofilm viability was reduced by >99.999% with both single and double exposures. This study shows that PDD is effective in eradicating planktonic and biofilm cultures of P. aeruginosa, supporting the concept that translation into clinical practice for indications such as otitis externa and wound disinfection is a viable option.     

Formation of novel sulfur-containing C60F16 cycloadducts between tetrathiafulvalene and C60F18; a unique six-electron cycloaddition of a fullerene involving F2 loss

Co-evaporation of solutions of C(60)F(18) and tetrathiafulvalene in toluene produces an unsymmetrical C(60)F(16):tetrathiafulvalene adduct through a unique six-electron cycloaddition involving displacement of two fluorine atoms by a terminal Cdbond;C double bond of the fulvalene. The adduct rearranges into two further adducts, one of which is characterised as a new type of fullerene derivative, a thiiranofullerene, formed by elimination of a thioketene moiety from the tetrathiafulvalene adduct. The initial addition also produces a bisadduct in which the addends comprise one tetrathiafulvalene molecule and one in which carbon disulfide has been eliminated. The latter adduct involves cycloaddition of an unsaturated aromatic dithiolactone moiety.     

Electrophilic substitution of C60F18 into phenols: HF elimination between OH and a 1,3-shifted fluorine giving benzofurano[2',3':10,26]hexadecafluro[60]fullerene and derivatives

The reaction of C60F18 with phenol, 2-naphthol and quinol in the presence of ferric chloride leads to initial electrophilic substitution (aryldefluorination). This occurs at both ortho and para positions for phenol, at the ortho position for quinol, and at the relatively hindered but most reactive 1-position for 2-naphthol. It is followed, where sterically favourable, by HF loss either between the OH group and F (rendered adjacent as a result of a 1,3-shift) or to attack of the OH group at an adjacent double bond with loss of a beta-fluorine, giving benzofurano[2',3':10,26]hexadecafluoro[60]fullerene derivatives. The reaction is accompanied by some complete defluorination leading, in reaction with phenol and with 2-naphthol, to the formation of benzofurano[2',3':1,2][60]fullerene and naphtho[2,1:b]furano[d:1,2][60]-fullerene, respectively. The mechanism of base-catalysed reaction of phenols with C60Cl6 is re-evaluated.