Palladium-catalyzed synthesis of substituted cyclopentadienes and indenes from allylic esters

Various mono- and di-substituted cyclopentadienes have been prepared by palladium-catalyzed alkylation of allylic esters with cyclopentadienide and t-butyl-cyclopentadienide anions. The same procedure has been applied to the preparation of substituted indenes.     

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.     

Synthesis, characterization and electrochemical studies of the heterometallic diclusters [{Fe2(μ-CO)(CO)6(μ-PPh2)Au}2(diphosphine)] (diphosphine=dppm, dppip, dppe, dppp)

Treatment of [(ClAu)₂(diphosphine)] {diphosphine=bis(diphenylphosphino)methane (dppm), bis(diphenylphosphino)isopropane (dppip), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp)} with two equivalents of the anion [Fe₂(μ-CO)(CO)₆(μ-PPh₂)]⁻ in the presence of TlBF₄ gives the new heterometallic diclusters [{Fe₂(μ-CO)(CO)₆(μ-PPh₂)Au}₂(diphosphine)] that have been isolated and characterized. Their ³¹P-NMR spectra show different patterns as a function of the diphosphine ligand. The electrochemical behavior of these compounds has been investigated and compared with that of the mono- [Fe₂(μ-CO)(CO)₆(μ-PPh₂)(μ-AuPPh₃)] and tricluster [{Fe₂(μ-CO)(CO)₆(μ-PPh₂)Au}₃(triphos)] derivatives.     

Matching unknown empirical formulas to chemical structure using LC/MS TOF accurate mass and database searching: example of unknown pesticides on tomato skins

Traditionally, the screening of unknown pesticides in food has been accomplished by GC/MS methods using conventional library searching routines. However, many of the new polar and thermally labile pesticides and their degradates are more readily and easily analyzed by LC/MS methods and no searchable libraries currently exist (with the exception of some user libraries, which are limited). Therefore, there is a need for LC/MS approaches to detect unknown non-target pesticides in food. This report develops an identification scheme using a combination of LC/MS time-of-flight (accurate mass) and LC/MS ion trap MS (MS/MS) with searching of empirical formulas generated through accurate mass and a ChemIndex database or Merck Index database. The approach is different than conventional library searching of fragment ions. The concept here consists of four parts. First is the initial detection of a possible unknown pesticide in actual market-place vegetable extracts (tomato skins) using accurate mass and generating empirical formulas. Second is searching either the Merck Index database on CD (10,000 compounds) or the ChemIndex (77,000 compounds) for possible structures. Third is MS/MS of the unknown pesticide in the tomato-skin extract followed by fragment ion identification using chemical drawing software and comparison with accurate-mass ion fragments. Fourth is the verification with authentic standards, if available. Three examples of unknown, non-target pesticides are shown using a tomato-skin extract from an actual market place sample. Limitations of the approach are discussed including the use of A + 2 isotope signatures, extended databases, lack of authentic standards, and natural product unknowns in food extracts.     

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 and structure of chiral-at-metal complexes with the ligand (S)-2-[(Sp)-2-(diphenylphosphino)ferrocenyl]-4-isopropyloxazoline

Half-sandwich complexes of formula [(ηⁿ-ring)MClL]PF₆ [L = (S)-2-[(S_p)-2-(diphenylphosphino)ferrocenyl]-4-isopropyloxazoline; (ηⁿ-ring)M = (η⁵-C₅Me₅)Rh; (η⁵-C₅Me₅)Ir; (η⁶-p-MeC₆H₄iPr)Ru; (η⁶-p-MeC₆H₄iPr)Os] have been prepared and spectroscopically characterised. The molecular structures of the rhodium and iridium compounds have been determined by X-ray crystallography. The related solvate complexes [(η⁵-C₅Me₅)ML(Me₂CO)]²⁺ (M = Rh, Ir) are active catalysts for the Diels-Alder reaction between methacrolein and cyclopentadiene.     

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.