N-α-Benzyloxyacetyl derivatives of (S)-4-benzyl-5,5-dimethyloxazolidin-2-one for the asymmetric synthesis of differentially protected α,β-dihydroxyaldehydes

α-Dibenzylamino- and α-benzyloxy- derivatives of N-acetyl-(S)-4-benzyl-5,5-dimethyloxazolidin-2-one readily undergo highly stereoselective boron mediated syn-aldol reactions with a range of aromatic and aliphatic aldehydes, generating the syn-aldol products in good to excellent yields as single diastereoisomers after purification. In the α-dibenzylamino series, deprotection of the functionalised aldol fragments to the corresponding α-amino-β-hydroxy methyl ester or α-amino-β-hydroxyaldehyde proved problematic, with a range of N- and O-protecting groups giving mixtures of products arising from endocyclic and exocyclic cleavage pathways. However, in the α-benzyloxy series, O-silyl protection of the aldol products, and subsequent DIBAL reduction gives stereoselectively the corresponding N-1′-hydroxyalkyloxazolidin-2-ones, which undergo base promoted fragmentation to the desired highly functionalised and differentially protected α,β-dihydroxyaldehydes in good yields and without loss of stereochemical integrity.     

Microheterogeneity in aqueous-organic solutions: Heat capacities,volumes and expansibilities of some alcohols,aminoalcohol and tertiary amines in water

The heat capacities per unit volume and the densities of aqueous solutions of 2-propanol, neopentanol, tert-amylalcohol, 2-amino-2-methylpropanol, triethylamine and diethylmethylamine were measured, in many cases as a function of temperature, over the whole mole fraction or solubility range. Apparent and partial molal heat capacities, volumes and expansibilities were derived. The concentration dependence of these functions suggest the existence of transitions in some of these systems, in the water-rich region, qualitatively similar to micellization. The large relaxation contribution observed with some of the thermodynamic functions of hydrophobic alcohols and amines suggests a reinforcement of hydrophobic hydration due to strong hydrogen-bonding interactions of the polar groups with water.     

Thermal decomposition of poly(vinylidene chloride) prepared in presence of oxygen

The thermal decomposition of poly(vinylidene chloride) was studied for samples prepared in the presence of oxygen. The products from both mass and aqueous suspension polymerizations show two modes of thermal decomposition. A rapid initial mode varies in rate and extent with the amount of oxygen present. A slower mode is unaffected by oxygen and in similar in rate to the polymer made in the absence of oxygen. The chief volatile products are phosgene and formaldehyde for the rapid decomposition and hydrogen chloride for the slow decomposition. The rapid decomposition is interpreted to be an unzipping reaction of a vinylidene chloride–oxygen alternating copolymer initiated by homolysis of a peroxide bond. The absence of significant amounts of hydrogen chloride during this stage of decomposition shows that none of the free radicals generated are capable of initiating a chain reaction that would unzip hydrogen chloride from the poly(vinylidene chloride) backbone. The presence of oxygen during the aqueous suspension polymerization correlates with the generation of hydrochloric acid in the aqueous phase. By analogy with the high temperature decomposition, the hydrochloric acid is believed to result primarily from the hydrolysis of phosgene produced by partial decomposition of the polyperoxide. Initiation of the decomposition is believed due to a reaction of the chain propagating radical.     

Solid-phase synthesis of imidazo[4,5-b]pyridin-2-ones and related urea derivatives by cyclative cleavage of a carbamate linkage

A solid-phase synthesis of substituted cyclic urea derivatives as potential heterocyclic library scaffolds is described. 2-Amino-3-nitropyridine is attached to Wang resin via a carbamate linkage. Reduction of the nitro group was achieved with SnCl(2).2H(2)O. Reductive alkylation with a range of substituted benzaldehydes followed by cyclative cleavage afforded a small library of 3-substituted imidazo[4,5-b]pyridine-2-ones in 33-45% yield and 59-88% purity. Subsequently, this methodology was applied to the synthesis of 3-substituted imidazo[4,5-f]quinolin-2-ones.     

Evaluation of an Economical Sunlamp that Emits a Near Solar UV Power Spectrum for Conducting Photoimmunological and Sunscreen Immune Protection Studies

Expense and inconvenience have restricted the use of the filtered xenon are lamp (solar simulator) as a UV source for conducting large-scale animal studies. Because sunscreen immunoprotective levels are significantly affected by the UV power spectrum of the source it is imperative that a solar simulating source be used for accurate measurements of sunscreen protection levels that are relevant to human UV exposures from sunlight. However, relatively inexpensive sunlamps, e. g. the UVA-340, that emit a UV power spectrum similar to that of a solar simulator are available. Unlike FS-type UVB sunlamps, which have a significant amount of effective immunosuppressive nonsolar UV energy at wavelengths below 295 nm, the immunosuppression effectiveness spectrum of UVA-340 sunlamps was nearly identical to that of a solar simulator. The purpose of this study was to evaluate this sunlamp for conducting photoimmunological and sunscreen immune protection studies. Groups of C3H mice were exposed to a range of UVA-340 sunlamp doses (0.25 KJ/m² to 20.0 KJ/m²) to establish a dose-response curve and determine the minimum immune suppression dose (MISD) for induction of local-type suppression of contact hypersensitivity (CH). The MISD, defined as the lowest UV dose given to produce ～50% suppression of the CH response in mice, was determined to be 1.0 kJ/m² for UVA-340 sunlamps. Immune protection tests on four marketed sunscreen lotions (sun protection factors [SPF] 4, 8, 15 and 30) were then conducted with UVA-340 sunlamps using MISD as the endpoint. The immune protection factors for these sunscreens were equivalent to the level of protection predicated by their labeled SPF. These results are similar to those we have previously obtained using a solar simulator. We conclude from these data that the immunosuppressive effects of UVA-340 sunlamps are similar to those of a solar simulator; however, further studies are needed to determine if UVA-340, or similar, sunlamps are a viable alternative to the solar simulator for conducting large-scale animal experiments that require a relevant UV solar spectrum.     

The potential of serially coupled alkyl-bonded silica monolithic columns for high resolution separations of pharmaceutical compounds in biological fluids

Summary In this paper we investigate the potential of alkyl-bonded silica monolithic columns for the isolation and identification of drug-related components in biological fluids. Up to 6 columns have been connected in series to produce a chromatographic system with up to 40,000 plates. This high-resolution chromatography system has been coupled to both MS and NMR to enable efficient detection and characterisation of drug-related components in biological fluids. The use of six coupled columns has been shown to give enhanced resolution over a high quality silica particulate column packed with 3 μm material which exhibits the same back pressure. The effect of volume and mass load on the performance of monolithic columns for semi-preparative chromatography of biological fluids has also been investigated. In these studies it was possible to inject up to 100 mL of neat urine with no loss of chromatographic performance. Furthermore, upon re-testing, the columns showed similar chromatographic performance. Again several columns were serially connected, producing enhanced resolution in the semi-preparative mode.     

IN VITRO STUDIES ON THE PHOTOSENSITIZED OXIDATION OF LENS PROTEINS BY PORPHYRINS

Abstract Porphyrins, which may be introduced into the eye as a result of abnormal porphyrin metabolism (uroporphyrin–Uro) or when used in the diagnosis or photodynamic therapy of certain tumors, including intraocular tumors (hematoporphyrin–Hp and'hematoporphyrin derivative'–Hpd and mesotetra( P -sulfonatophenyl)porphyrin–TPPS) are efficient photosensitizers in biological systems. We have been studying the potential phototoxic side effects of these drugs in the lens of the eye. Encapsulated in the human lens is a mixture of soluble protein crystallins. With little turnover of protein in the lens, any photosensitized modifications will accumulate and may result in an opacification of the lens. To evaluate the potential of different porphyrins to induce such damage, a series of porphyrins were photolyzed (transmission above 295 nm) in the presence of calf lens protein (2 mg m⁻¹). Marked photopolymerization and histidine destruction were observed for the lens protein photolyzed in the presence of all of the drugs. We have found that the relative effectiveness of the following porphyrins to induce that damage is: Uro = TPPS Hpd = Hp. Both the singlet oxygen quencher, azide, and the free radical scavenger, penicillamine, decrease this photosensitized oxidative damage to lens protein. TPPS binds significantly to lens protein and this binding leads to conformational changes in that protein.     

Synthesis of a simplified bryostatin C-ring analogue that binds to the CRD2 of human PKC-alpha and construction of a novel BC-analogue by an unusual Julia olefination process

[structure: see text] The synthesis of two truncated bryostatin analogues 2 and 3 is described. High-field NMR measurements on the C-ring analogue 3 in C(2)H(3)CN containing 25% (2)H(2)O have shown that it binds to the CRD2 of human PKC-alpha at virtually the same position as phorbol-13-acetate (PA) and bryostatin 1 (1). NMR titration studies have also revealed that 3 binds to the CRD2 with a potency similar in magnitude to PA but much less potently than 1.     

Optical activity in the biaryl series

The relationship between the CD spectra of the chiral biaryls and their stereochemical configuration, as a function of the dihedral angle between the molecular planes of the aromatic moieties, has been investigated for biphenyl, 1,1′-binaphthyl, 1,1′-bianthryl and 9,9′-bianthryl in the exciton approximation and, for the 1,1′-binaphthyls, in the π-SCF approximation. Both methods provide unambiguous assignments of absolute configuration except for biaryls with a critical dihedral angle of π/2 in those with effective D_data2 chromophoric symmetry, or 100–110° in the case of the 1,1′-binaphthyls.