Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

The conformation of amine- and amide-terminated poly(propylene imine) dendrimers as investigated by molecular simulation methods

The parameters that influence the conformation of poly(propylene imine) dendrimers were investigated by molecular simulations using molecular mechanics and simulated annealing methods. Dendrimers with two types of peripheral units able to communicate via hydrogen bonding-amine and amide moieties-were considered in order to study the role that secondary interactions among the end groups have in the spatial organization of the dendritic branches. Radial atomic density profiles and radial atomic probability distributions were used to extract global properties, such as the degree of packing of the branches, the distribution of the monomers throughout the molecular volume, and the extent and characteristics of the surface region. Information was also obtained about the nature, location, and extent of formation of the hydrogen bonds, as well as their evolution with dendrimer generation and their assembly into networks. The analyses were supported by a detailed investigation of the first two generations, with an emphasis on the relationship between hydrogen bonding and the compactness and stability of the molecules; this allowed us to account for the generational evolution of hydrogen bonding that is experimentally observed in several poly(propylene imine) dendrimers.     

INTERACTIONS AND PHOTOREACTIVITY OF 5-ALKOXYPSORALENS WITH THYMINE. A MODEL APPROACH

Abstract— In order to investigate the interactions and the photoreactions in solution between the thymine (thy) and the psoralen (Pso) rings, we have prepared model compounds Thy-(CH₂)_n-Pso in which two aromatic chromophores Thy and Pso are linked by flexible polymethylene chains of varying length (CH₂)_n. Two series of compounds were examined and compared as models for the two important drugs 5-methoxypsoralen and 8-methoxypsoralen. Results concerning the 5-alkoxypsoralen series are reported here. In water, these model molecules exhibit intramolecular ring-ring stacking interactions as indicated by hypochromism in the UV and by shielding of the protons in ¹H NMR spectroscopy. These interactions disappear in organic solvents. The photochemical properties of the models were examined in relation with their ground state interaction properties. Irradiation at 365 nm carried out at the usual concentrations (10^-2-10^-3 M) leads exclusively to a stereoselective dimerization involving the psoralen moieties of the models at the 3,4 double bonds. However, when operating at exceedingly low concentrations (2 × 10^-5 M ), the psoralen photodimerization is avoided and a highly regio and stereo-selective psoralen thymine photoaddition is observed involving the 3,4 double bond of psoralen leading to the cis adduct. The same reaction occurs for all models under study being independent of the length of the (CH₂)_n polymethylene linking chain, n = 2 to 6, 12 and of the solvent used. This is unambiguous proof for the highest intrinsic photoreactivity of the 3,4 vs the 4',5' double bond in 5-alkoxy psoralen.     

Stereochemistry of Dehydrogenation of 1,4,-Cyclohexadiene with 2,3-Dichloro-5,6-dicyano-p-benzoquinone

cis- and trans-(3,6-D₂)-1,4-cyclohexadienes 1a and 1b have been synthesized from cis-3,4-dichlorocyclobutene (5). Aromatization to benzene with DDQ is cis-stereospecific with an uncertainty of 5%. This result is discussed in relation to concerted or stepwise mechanisms for aromatization of 1,4-dihydroaromatics with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ).     

Thermodynamic properties of alkali halides. V. Temperature and pressure dependence of excess free energies in water

A simple equation has been derived relating the temperature dependence of activity functions with excess enthalpies and excess heat capacities. Using experimentally determined parameters at 298.15°K, it is possible to predict osmotic coefficients and mean activity coefficients of alkali halides in water up to 1 m from 273°K to about 350°K. In general, the predicted functions agree with the measured values within the uncertainty of the activity data. An equation is also given for the pressure dependence of the excess free energies, but it was not possible to check the limitation of this equation due to lack of activity data at various pressures.To whom correspondence should be addressed.     

Synthesis of a New Bivalent Hirudin Analog (hirufos), which includes a stable 4′-phosphono-L-phenylalanine mimic of (L-tyrosine O4-sulfate)-63

The synthesis on solid phase of a new derivative of the anticoagulant protein hirudin is described (see Scheme and Fig.1, I ). The henicosapeptide is a bivalent conjugate of the C-terminus of hirudin and of the active-site-binding tetrapeptide D -Phe-Pro-Arg-Pro linked via a tetraglycine spacer. The peptide, for which the name hirufos was coined, incorporates a stable phosphono derivative of L -phenylalanine which, combined with the other structural modifications, leads to a potent anticoagulant agent. Synthesis was readily achieved by the (9H-fluoren-9-yl)-methoxycarbonyl (Fmoc) strategy followed by acidolytic cleavage from the resin and deprotection, including the liberation of the crucial phosphonic group on L -phenylalanine.     

Photochemistry of polymeric systems. I. Photocrosslinking of polymers and copolymers containing pyridine N-oxide groups

Vinylpyridine-N-oxide units were introduced in polymeric chains in order to study their photocrosslinking. Copolymers of styrene and 4-vinylpyridine-N-oxide were especially synthesized and studied. The methods used for characterization of photocrosslinked films were a “photoresist test” or the measurement of the insolubility and of the swelling ratio. The Cleavage of the N-oxide bond was responsible for the photocrosslinking. The competitive formation of carbonyl compounds took place and decreased the rate of photocrosslinking. This last reaction is favored by triplet-state quenchers. The photosensitivity of the copolymers was determined as a function of the wavelength of the radiation used. When the photocrosslinking proceeded, a film of the copolymeric material became transparent in the 280–320-nm range. Thick films could therefore be completely photocrosslinked when irradiated in this range of wavelength.     

Delocalization in platinum-alkynyl systems: a metal-bridged organic mixed-valence compound

A complex featuring two triarylamine redox centers bridged by Pt, trans-bis(triethylphosphine)-bis{4-[bis(4-methoxyphenyl)amino]phenylethynyl} platinum(II), has been synthesized as a model system for pi-conjugated Pt-containing polymers. Analysis of the intervalence charge-transfer band displayed by its mixed-valence monocation affords a quantitative assessment of electronic delocalization through the Pt bridge; this is found to be only slightly smaller than that determined for a benzene-bridged analogue. These results are supported by density functional theory calculations, which show that the active orbitals involved in the electron-transfer process in both cases have similar delocalization through the bridging unit.     

Analysis of basic compounds at high pH values by reversed-phase liquid chromatography

Reversed phase high performance liquid chromatography (RPLC) is currently the method of choice for the analysis of basic compounds. However, with traditional silica materials, secondary interactions between the analyte and residual silanols produce peak tailing which can negatively affect resolution, sensitivity, and reproducibility. In order to reduce these secondary interactions, which comprise ion exchange, hydrogen bonding, and London forces interactions, chromatographic analyses can be carried out at low or high pH values where silanol groups and basic compounds are mostly uncharged. The chromatographic behaviour of a particular bidentate stationary phase, Zorbax Extend C18, was studied with a set of basic and neutral compounds. Thanks to a higher chemical stability than traditional silica based supports, analyses were carried out with a high pH mobile phase, which represents a good alternative to the acidic mobile phases generally used to reduce ion exchange interactions. The performance of this bidentate stationary phase was also compared with that of other supports and it was proved that it is advantageous to work with high pH mobile phases when analyzing basic compounds.     

Quartic equations and classification of Riemann tensors in general relativity

For space-times in general relativity, the Petrov classification of the Weyl conformai curvature and the Plebaski or Segre classification of the Ricci tensor each depend on the properties of the roots of quartic equations. The coefficients in these quartic equations are in general complicated functions of the space-time coordinates. We review the general theory of quartic equations, and discuss algorithms for determining the existence and values of multiple roots. We consider practical implementation of an algorithm and the consequent Petrov classification. Tests of programs embodying this algorithm, using the computer algebra system CLASSI based on SHEEP, are reported.