A new two-step four-component synthesis of highly functionalized cyclohexenols by sequential nickel-catalyzed couplings

A new two-step procedure for the synthesis of cyclohexenols has been developed. A nickel-catalyzed three-component addition of an enal, alkyne, and acetylenic tin affords substituted hept-4-en-6-ynals. The products of this first step then undergo a second nickel-catalyzed reaction with organozincs or organoboranes to afford densely functionalized cyclohexenols. Variation in each of the four components is tolerated to provide access to a wide range of versatile building blocks.     

Structural investigation of 3,5‐disubstituted isoxazoles by 1H‐nuclear magnetic resonance

HIV‐1 integrase (IN) is a very promising and validated target for the development of therapeutic agents against AIDS. In an effort to design and synthesize biological isosteric analogs of β‐diketoacid‐containing inhibitors of IN, we prepared a series of substituted isoxazole carboxylic acids. Several of these compounds inhibited catalytic activities of purified IN at micromolar concentration range. With an aim to prepare a large number of analogues based on the isoxazole pharmacophore we focused our study on a series of 3,5‐disubstituted isoxazole isomers. For a rapid structural analysis we discovered a convenient ¹H‐nmr method for distinguishing between isomeric structures based on their H‐4 assignments. This “finger print” approach to isomer identification will be useful in combinatorial chemistry settings where a mixture can be further derivatized.     

New aspects in the reaction of azomethines with cyclic CH-acidic compounds

Summary Treatment of substituted benzylidene anilines1 a – df with cyclic CH-acidic compounds2a–m in ethanol at room temperature yields in additon/elimination reactions the corresponding arylidene derivatives4 and the 2:1 adducts5. The addition products3, which are formed as intermediates, could not be isolated in any case. The donor/acceptor effect of the substituents on the benzylidene moiety influences to a significant extent the reactivity towards the azomethine carbon.

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Neue Aspekte der Reaktion von Azomethinen mit cyclischen CH-aciden Verbindungen

Zusammenfassung Bei der Umsetzung der substituierten Benzylidenaniline1 a – f mit den cyclischen CH-aciden Verbindungen2 a – m in Ethanol bei Raumtemperatur erhält man in Additions/Eliminierungsreaktionen die Arylidenderivate4 und die 2:1-Addukte5. Die als Intermediat gebildeten Additionsprodukte3 konnten in keinem Fall isoliert werden. Die Donor-bzw. Acceptorwirkung der Substituenten am Benzylidenrest beeinflußt maßgebend die Reaktivität am Azomethinkohlenstoff.

     

Selective synthesis of isobutanol by means of the Guerbet reaction: Part 2. Reaction of methanol/ethanol and methanol/ethanol/n-propanol mixtures over copper based/MeONa catalytic systems

The synthesis of isobutanol via the Guerbet condensation between methanol and ethanol was studied by using sodium methoxide (MeONa) as soluble basic component and copper-based catalysts as heterogeneous dehydrogenating/hydrogenating metal species. The effect of the nature of the catalyst and the relative amount of its individual components with respect to the reacting alcohols as well as of temperature on productivity and selectivity of the process was investigated. The collected data indicated that the copper chromite/MeONa was more active than Cu-Raney/MeONa system. The reaction was shown to proceed with the formation only of n-propanol and isobutanol. Ethanol conversion up to 61% with selectivity to isobutanol up to 98.4% was obtained. The same catalytic systems were also employed in the reaction of the methanol/ethanol/n-propanol ternary mixture. Again copper chromite/MeONa resulted more active than the Cu-Raney/MeONa system. Finally, experiments were carried out on methanol/n-propanol mixtures in the presence of the copper chromite/MeONa catalytic system by recycling both the recovered solid copper component and the liquid reaction mixture for evidencing eventual copper leaching by MeONa. On the basis of the obtained results it was concluded that in the Guerbet reaction copper chromite works as heterogeneous catalyst.     

Electrochemical monitoring of indigo preparation using Maya’s ancient procedures

The preparation of indigo from Indigofera suffruticosa following the procedures attributed to ancient Mayas was electrochemically monitored using the voltammetry-of-microparticles approach. The mechanism formation of indigotin and indirubin from its precursors, indican and isatan, is discussed. Comparison of voltammetric profiles for differently prepared and commercial indigos and genuine Maya Blue samples suggests that the preparation procedure of indigo changed during the Late Classical Maya period. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Preparation and spectroscopic studies of some cyclic urea adducts of triphenyl-tin and -lead halides

1,3-Dimethyl-2-imidazolidinone (dimethylethylene urea, DMEU) and 1,3-di- methyl-3,4,5,6-tetrahydro-2(IH)-pyrimidinone (dimethylpropylene urea, DMPU) adducts of the type Ph₃SnX·L (X = Cl, Br and I), Ph₃PbX·L (X = Br, I), 3Ph₃PbCl·2DMEU and 2Ph₃PbCl · DMPU have been prepared and characterized. Assignments are made for ν(CO) and ν(CN) frequencies in the IR, and for skeletal frequencies observed in both the IR and Raman spectra in the range 400 to 100 cm^?1 Infrared measurements show that the adducts are bound through the carbonyl oxygen, and are highly dissociated in dichloromethane solution. ¹H and ¹¹⁹Sn or ²⁰⁷Pb NMR measurements reveal that ligand exchange, fast on the NMR time scale, occurs in solution. Coordination of the ligand causes a large upfield shift in the ¹¹⁹Sn or ²⁰⁷Pb resonances, but Ph₃MI · L have shifts similar to those for the parent iodides, indicating almost complete dissociation. Thermodynamic parameters are reported for the dissociation of Ph₃SnX · DMPU (X = Cl, Br) in CH₂Cl₂ solution.     

Mass spectrometric characterization of two novel inflammatory peptides from the venom of the social wasp Polybia paulista

The social wasp P. paulista is relatively common in southeast Brazil causing many medically important stinging incidents. The seriousness of these incidents is dependent on the amount of venom inoculated by the wasps into the victims, and the characteristic envenomation symptoms are strongly dependent on the types of peptides present in the venom. In order to identify some of these naturally occurring peptides available in very low amounts, an analytical protocol was developed that uses a combination of reversed-phase and normal-phase high-performance liquid chromatography (HPLC) of wasp venom for peptide purification, with matrix-assisted laser desorption/ionization time-of-flight post-source decay mass spectrometry (MALDI-Tof-PSD-MS) and low-energy collision-induced dissociation (CID) in a quadrupole time-of-flight tandem mass spectrometry (QTof-MS/MS) instrument for peptide sequencing at the sub-picomole level. The distinction between Leu and Ile was achieved both by observing d-type fragment ions obtained under CID conditions and by comparison of retention times of the natural peptides and their synthetic counterparts (with different combinations of I and/or L at N- and C-terminal positions). To distinguish the isobaric residues K and Q, acetylation of peptides was followed by Q-Tof-MS analysis. The primary sequences obtained were INWLKLGKMVIDAL-NH(2) (MW 1611.98 Da) and IDWLKLGKMVMDVL-NH(2) (MW 1658.98 Da). Micro-scale bioassay protocols characterized both peptides as presenting potent hemolytic action, mast cell degranulation, and chemotaxis of polymorphonucleated leukocyte (PMNL) cells. The primary sequences and the bioassay results suggest that these toxins constitute members of a new sub-class of mastoparan toxins, directly involved in the occurrence of inflammatory processes after wasp stinging.     

Determination of rotational barriers of carbon?carbon bonds in 2-arylpiperidines

Carbon-carbon sp³-sp² rotational barriers of 3,3-dimethyl-2-(3,4,5-trimethoxyphenyl)-4-piperidones and their ethylene ketals have been evaluated using nmr techniques. The conformation of 1 hydrochloride has been studied by NOE determinations. Values found for the hydrochlorides of the title compounds are discussed in terms of equilibria with free bases and nitrogen inversion.     

Reactivity and reaction pathways of electrochemically generated 17-electron tricarbonyl steroid chromium cations

Electrochemical oxidation of α- and β-diastereomers of a range of steroid hormone receptor marker chromium tricarbonyl complexes, (steroid)Cr(CO)₃, have been examined at platinum electrodes in dichloromethane. Data confirm the general nature of previously published conclusions on the oxidation of (arene)Cr(CO)₃ complexes (arene = benzene or steroid). That is, with 0.1 M Bu₄NPF₆ as the electrolyte, and in the absence of nucleophiles, a reversible oneelectron process, (steroid)Cr(CO)₃ ? [(steroid)Cr(CO)₃]⁺ + e^?, is observed, followed by an irreversible one-electron process at considerably more positive potentials. The reversible half-wave potentials (approximately E°-values) calculated for the [(steroid)Cr(CO)₃]⁺/(steroid)Cr(CO)₃ redox couple are shown to be dependent on whether the α- or β-diastereomer is oxidized. Similarly the rate of nucleophilic attack on the 17-electron cation [(steroid)Cr(CO)₃]⁺ by nucleophiles such as ClO, PPh₃ and bis(diphenylphosphine)methane confirms a previous observation that the stereochemistry of this class of compound is important with respect to redox, kinetic and hormone receptor properties. The nature of the electrochemical data obtained on the (arene)Cr(CO)₃ complexes in the presence of nucleophiles suggests that reactions associated with the nucleophilic attack on the 17-electron cations are complex and that a range of reaction pathways occur simultaneously. Electrochemical studies on the oxidation of (benzene)Cr(CO)₂PPh₃ and (oestradiol)Cr(CO)₂PPh₃ confirm some aspects of the proposed mechanisms, although it is clear that a great deal still has to be learned concerning mechanistic aspects of nucleophilic attack on these 17-electron complexes.     

Mesoscopic chiral reshaping of the Ag(110) surface induced by the organic molecule PVBA

We report scanning tunneling microscopy observations on the restructuring of a Ag(110) surface induced by the molecule 4-[trans-2-(pyrid-4-yl-vinyl)]benzoic acid (PVBA). Our data reveal that the surface undergoes a mesoscopic step faceting following exposure to submonolayer coverages and thermal activation. A sawtooth arrangement evolves implying long-range mass transport of substrate atoms and forming a regular arrangement of kink sites. Its formation is associated with the molecules' functional headgroups forming carboxylates with [100] Ag microfacets at step edges, and eventually operating to reshape the surface morphology. Interestingly, the resulting microfacets act as chiral templates for the growth of supramolecular PVBA structures. Theoretical modeling based on ab initio results indicates that chiral recognition processes discriminating between the two enantiomers of adsorbed PVBA molecules occur in this process.