Synthesis and characterization of the atropisomeric relationships of a substituted N-phenyl-bipyrazole derivative with anti-inflammatory properties

This work describes the atropisomeric relationships of 3-methyl-5-(3-methyl-5-phenyl-1H-pyrazol-1-yl)-1-phenyl-1H-pyrazol-4-amine (2d), which belongs to series 4-aminobipyrazole derivatives designed as anti-inflammatory agents. The 1H nuclear magnetic resonance spectra obtained in the presence of a chiral lanthanide shift salt associated to chiral high-performance liquid chromatography analysis, X-ray diffraction, and molecular modeling tools confirmed that ortho bis-functionalized bipyrazole 2d exists as a mixture of aR,aS-atropisomers. These results provide useful information to understand the pharmacological profile of this derivative and of other 4-aminobipyrazole analogs. Chirality 24:463470, 2012. (c) 2012 Wiley Periodicals, Inc.

Solid phase microextraction and LC-MS/MS for the determination of paliperidone after stereoselective fungal biotransformation of risperidone

The present work describes for the first time the use of SPME coupled to LC-MS/MS employing the polar organic mode in a stereoselective fungal biotransformation study to investigate the fungi ability to biotransform the drug risperidone into its chiral and active metabolite 9-hydroxyrisperidone (9-RispOH). The chromatographic separation was performed on a Chiralcel OJ-H column using methanol:ethanol (50:50, v/v) plus 0.2% triethylamine as the mobile phase at a flow rate of 0.8 mL min(-1). The SPME process was performed using a C18 fiber, 30 min of extraction time and 5 min of desorption time in the mobile phase. The method was completely validated and all parameters were in agreement with the literature recommendations. The Cunninghamella echinulata fungus was able to biotransform risperidone into the active metabolite, (+)-9-RispOH, resulting in 100% of enantiomeric excess. The Cunninghamella elegans fungus was also able to stereoselectively biotransform risperidone into (+)- and (-)-9-RispOH enantiomers at different rates. (C) 2012 Elsevier B.V. All rights reserved.

Lipase-catalyzed kinetic resolution of beta-borylated carboxylic esters

The kinetic resolution of chiral beta-borylated carboxylic esters via lipase-catalyzed hydrolysis and transesterification reactions was studied. The enantioselective hydrolysis catalyzed by CAL-B furnished the beta-borylated carboxylic acid with reasonable enantiomeric excess (62% ee), while both methyl and ethyl beta-borylated carboxylic esters were recovered with excellent ee (>99%). Meanwhile, the transesterification reaction of beta-borylated carboxylic esters and several alcohols, catalyzed by CAL-B, only indicated a high selectivity when ethanol and methyl-(beta-pinacolylboronate)-butanoate were used as substrates, which gave ethyl-(beta-pinacolylboronate)-butanoate with >99% ee. (C) 2012 Elsevier Ltd. All rights reserved.

VCD to determine absolute configuration of natural product molecules: secolignans from Peperomia blanda

The absolute configuration and solution-state conformers of three peperomin-type secolignans isolated from Peperomia blanda (Piperaceae) are unambiguously determined by using vibrational circular dichroism (VCD) spectroscopy associated with density functional theory (DFT) calculations. Advantages of VCD over the electronic form of CD for the analysis of diastereomers are also discussed. This work extends our growing knowledge about secondary metabolites within the Piperaceae family species while providing a definitive and straightforward method to assess the absolute stereochemistry of secolignans.

Further monoterpene chromane esters from Peperomia obtusifolia: VCD determination of the absolute configuration of a new diastereomeric mixture

A reinvestigation of the monoterpene chromane ester enriched fraction from Peperomia obtusifolia using chiral chromatography led to the identification of a minor peak, which was elucidated by NMR and HRMS as fenchyl-3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3 ''-methyl-2 ''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2H-1-benzopyran-6-carboxylate, the same structure assigned to two other fenchyl esters described previously, pointing out a stereoisomeric relationship among them. Further NMR analysis revealed that it was actually a mixture of two compounds, whose absolute configurations were determined by VCD measurements. Although, almost no vibrational transitions could be assigned to the chiral chromane, the experimental VCD spectrum was largely opposite to that obtained for the average experimental VCD [(2S,1'''R,2'''R,4'''S + 2R,1'''R,2'''R,4'''S)/2] for fenchol derivatives. These results allowed us to assign the putative compounds as a racemic mixture of the chiral chromane esterified with the monoterpene (1S,2S,4R)fenchol, which had not been identified in our early work. (C) 2012 Elsevier Ltd. All rights reserved.

Polyazomethine with vinylene and phenantridine moieties in the main chain: Synthesis, characterization, opto(electrical) properties and theoretical calculations

The opto(electrical) properties and theoretical calculations of polyazomethine with vinylene and phenantridine moieties in the main chain were investigated in the present study. 2,5-Bis(hexyloxy)-1,4-bis[(2,5-bis(hexyloxy)-4-formyl-phenylenevinylene]benzene was polymerized in solution with 3,8-diamino-6-phenylphenanthridine (PAZ-PV-Ph). The temperatures of 5% weight loss (T-5%) of the polyazomethine was observed at 356 degrees C in nitrogen. Electrochemical properties of thin film of the polymer were studied by differential pulse voltammetry. The HOMO level of the PAZ-PV-Ph was at -4.97 eV. The energy band gap (E-g) was detected of approximately similar to 1.9 eV. Energy band gap (E-gopt) was additionally calculated from absorption spectrum and absorption coefficient alpha. The absorption UV-vis spectra of polyazomethine recorded in solution showed a blue shift in comparison with the solid state. HOMO-LUMO levels and E-g were additionally calculated theoretically by density functional theory and molecular simulations of PAZ-PV-Ph are presented. Current density-voltage (J-U) measurements were performed on ITO/PAZ-PV-Ph/Al, ITO/TiO2/PAZ-PV-Ph/Al and ITO/PEDOT/PAZ-PV-Ph:TiO2/Al devices in the dark and during irradiation with light (under illumination of 1000 W m(-2)). The polymer was tested using AFM technique and roughness (R-a, R-ms) along with skew and kurtosis are presented.

Kinetic resolution of alpha-bromophenylacetamides using quinine or Cinchona alkaloid salts

The kinetic resolution of racemic alpha-bromophenylacetamides 1 was achieved in the presence of benzenethiolate and Cinchona alkaloid salts as phase-transfer catalysts or benzenethiol and quinine, yielding (S)-enantioenriched alpha-sulfanylated products. The observed stereoselection was rationalized on the basis of the best fitting of 1 and the resolving agent in the ternary complexes. (C) 2012 Elsevier Ltd. All rights reserved.

Hadronic molecules with both open charm and bottom

With the one-boson-exchange model, we study the interaction between the S-wave D(*)/D-s(*) meson and S-wave B(*)/B-s(*) meson considering the S-D mixing effect. Our calculation indicates that there may exist the B-c-like molecular states. We estimate their masses and list the possible decay modes of these B-c-like molecular states, which may be useful to the future experimental search.

Exploiting the enantioselectivity of Baeyer-Villiger monooxygenases via boron oxidation

The enantioselective carbon-boron bond oxidation of several chiral boron-containing compounds by Baeyer-Villiger monooxygenases was evaluated. PAMO and M446G PAMO conveniently oxidized 1-phenylethyl boronate into the corresponding 1-(phenyl)ethanol (ee = 82-91%). Cyclopropyl boronic esters were also oxidized but with no enantioselectivity. beta-Boryl carboxylic esters were not oxidized by any BVMOs. (C) 2012 Elsevier Ltd. All rights reserved.

1(--) and 0(++) heavy four-quark and molecule states in QCD

We estimate the masses of the 1(--) heavy four-quark and molecule states by combining exponential Laplace (LSR) and finite energy (FESR) sum rules known perturbatively to lowest order (LO) in alpha(s) but including non-perturbative terms up to the complete dimension-six condensate contributions. This approach allows to fix more precisely the value of the QCD continuum threshold (often taken ad hoc) at which the optimal result is extracted. We use double ratio of sum rules (DRSR) for determining the SU(3) breakings terms. We also study the effects of the heavy quark mass definitions on these LO results. The SU(3) mass-splittings of about (50-110) MeV and the ones of about (250-300) MeV between the lowest ground states and their 1st radial excitations are (almost) heavy-flavor independent. The mass predictions summarized in Table 4 are compared with the ones in the literature (when available) and with the three Y-c(4260, 4360, 4660) and Y-b(10890) 1(--) experimental candidates. We conclude (to this order approximation) that the lowest observed state cannot be a pure 1(--) four-quark nor a pure molecule but may result from their mixings. We extend the above analyzes to the 0(++) four-quark and molecule states which are about (0.5-1) GeV heavier than the corresponding 1(--) states, while the splittings between the 0(++) lowest ground state and the 1st radial excitation is about (300-500) MeV. We complete the analysis by estimating the decay constants of the 1(--) and 0(++) four-quark states which are tiny and which exhibit a 1/M-Q behavior. Our predictions can be further tested using some alternative non-perturbative approaches or/and at LHCb and some other hadron factories. (c) 2012 Elsevier B.V. All rights reserved.

História da propagação das citações originais do artigo do Journal of Quantitative Spectroscopy & Radiative Transfer 102/441/2006.

Neste artigo procuraremos descrever a história cronológica das citações originais (aquelas que os nomes dos autores aparecem apenas uma vez, portanto, excluídas as autocitações) da publicação do artigo: M. Cattani and J. M. F. Bassalo, Racemization, Chiral Stability and Weak Interactions, Journal of Quantitative Spectroscopy & Radiative Transfer 102, pp. 441-449, 2006 (CB: JQS&RT 102/441/2006). Para realizar essa história, usamos a WEB OF SCIENCE (acessado: 08/02/2013) disponibilizado pela CAPES/UFPA.

Some aspects of self-duality and generalised BPS theories

If a scalar eld theory in (1+1) dimensions possesses soliton solutions obeying rst order BPS equations, then, in general, it is possible to nd an in nite number of related eld theories with BPS solitons which obey closely related BPS equations. We point out that this fact may be understood as a simple consequence of an appropriately generalised notion of self-duality. We show that this self-duality framework enables us to generalize to higher dimensions the construction of new solitons from already known solutions. By performing simple eld transformations our procedure allows us to relate solitons with di erent topological properties. We present several interesting examples of such solitons in two and three dimensions.

Optically active photoresponsive multifunctional polymeric materials

In the last year [1], Angiolini and co-workers have synthesized and investigated methacrylic polymers bearing in the side chain the chiral cyclic (S)-3-hydroxypyrrolidine moiety interposed between the main chain and the trans-azoaromatic chromophore, substituted or not in the 4’ position by an electron-withdrawing group. In these materials, the presence of a rigid chiral moiety of one prevailing absolute configuration favours the establishment of a chiral conformation of one prevailing helical handedness, at least within chain segments of the macromolecules, which can be observed by circular dichroism (CD). The simultaneous presence of the azoaromatic and chiral functionalities allows the polymers to display both the properties typical of dissymmetric systems (optical activity, exciton splitting of dichroic absorptions), as well as the features typical of photochromic materials (photorefractivity, photoresponsiveness, NLO properties). The first part of this research was to synthesize analogue homopolymers and copolymers based on bisazoaromatic moiety and compare their properties to those of the above mentioned analogue derivatives bearing only one azoaromatic chromophore in the side chain. We focused also the attention on the effects induced on the thermal and chiroptical behaviours by the insertion of particulars achiral comonomers characterized by different side-chain mobility and grown hindrance (MMA, tert-BMA and TrMA). On the other hand carbazole containing polymers [2] have attracted much attention because of their unique features. The use of these materials in advanced micro- and nanotechnologies spreads in many different applications such as photoconductive and photorefractive polymers, electroluminescent devices, programmable optical interconnections, data storage, chemical photoreceptors, NLO, surface relief gratings, blue emitting materials and holographic memory. The second part of the work was focused on the synthesis and the characterization polymeric derivatives bearing in the side chain carbazole or phenylcarbazole moieties linked to the (S)- 2-hydroxy succinimide or the (S)-3-hydroxy pyrrolidinyl ring as chiral groups covalently linked to the main chain through ester bonds. The last objective of this research was to design, synthesize, and characterize multifunctional methacrylic homopolymers and copolymers bearing three distinct functional groups (i.e. azoaromatic, carbazole and chiral group of one single configuration) directly linked in the side chain. This polymeric derivatives could be of potential interest for several advanced application fields, such as optical storage, waveguides, chiroptical switches, chemical photoreceptors, NLO, surface relief gratings, photoconductive materials, etc.

Sintesi e coordinazione di leganti Ciclopentadienilici O-Multifunzionalizzati

The introduction of hydroxyl groups into ligands is able to transfer high hydrophilic features to the related metal systems. The atom-economy synthetic procedure adopted which consists in the one-step Cyclopentene-oxide ring opening, quantitatitatively affords stereoselective formation of the multi-hydroxyl rac-1,2,4- C5H2[CH(CH2)3CHOH]3 Cpººº ligand1. Rh complexation of Cpººº gives rise to a novel class of water-soluble complexes (L,L)RhCpººº (LL=NBD 1, COD 2, CH2CH2 3, CO 4) (Scheme 1) characterized by their spectroscopic features (ESI-MS, IR, 2D NMR, n.O.e.). The X-ray diffraction studies of 1a reveal the occurrence of one couple of enantiomeric pairs in the crystal structure, whilst the crystal packing shows an interesting self-organization in chains of dimeric units of 1a, promoted by strong intermolecular hydroxyl H-bonding. This effect has been exploited by performing VT NMR experiments in different solvents (CDCl3, Py, DMSO). Unpredictably, in the absence of chiral tag, 1 exhibits solvent-dependent chiroptical properties (CD, αD^ 25), which are correlated to UV transitions and DFT calculations. The intra/inter molecular H-binding is crucial in driving the equilibrium between the observed atropisomers 1a and 1b, by varying the planar chirality on the two π-complexes.

Organocatalytic asymmetric mannich-type reactions: an easy approach to optically active amine derivatives

The topics I came across during the period I spent as a Ph.D. student are mainly two. The first concerns new organocatalytic protocols for Mannich-type reactions mediated by Cinchona alkaloids derivatives (Scheme I, left); the second topic, instead, regards the study of a new approach towards the enantioselective total synthesis of Aspirochlorine, a potent gliotoxin that recent studies indicate as a highly selective and active agent against fungi (Scheme I, right). At the beginning of 2005 I had the chance to join the group of Prof. Alfredo Ricci at the Department of Organic Chemistry of the University of Bologna, starting my PhD studies. During the first period I started to study a new homogeneous organocatalytic aza-Henry reaction by means of Cinchona alkaloid derivatives as chiral base catalysts with good results. Soon after we introduced a new protocol which allowed the in situ synthesis of N-carbamoyl imines, scarcely stable, moisture sensitive compounds. For this purpose we used α-amido sulfones, bench stable white crystalline solids, as imine precursors (Scheme II). In particular we were able to obtain the aza-Henry adducts, by using chiral phase transfer catalysis, with a broad range of substituents as R-group and excellent results, unprecedented for Mannich-type transformations (Scheme II). With the optimised protocol in hand we have extended the methodology to the other Mannich-type reactions. We applied the new method to the Mannich, Strecker and Pudovik (hydrophosphonylation of imines) reactions with very good results in terms of enantioselections and yields, broadening the usefulness of this novel protocol. The Mannich reaction was certainly the most extensively studied work in this thesis (Scheme III). Initially we developed the reaction with α-amido sulfones as imine precursors and non-commercially available malonates with excellent results in terms of yields and enantioselections.3 In this particular case we recorded 1 mol% of catalyst loading, very low for organocatalytic processes. Then we thought to develop a new Mannich reaction by using simpler malonates, such as dimethyl malonate.4 With new optimised condition the reaction provided slightly lower enantioselections than the previous protocol, but the Mannich adducts were very versatile for the obtainment of β3-amino acids. Furthermore we performed the first addition of cyclic β-ketoester to α-amido sulfones obtaining the corresponding products in good yield with high level of diastereomeric and enantiomeric excess (Scheme III). Further studies were done about the Strecker reaction mediated by Cinchona alkaloid phase-transfer quaternary ammonium salt derivatives, using acetone cyanohydrin, a relatively harmless cyanide source (Scheme IV). The reaction proceeded very well providing the corresponding α-amino nitriles in good yields and enantiomeric excesses. Finally, we developed two new complementary methodologies for the hydrophosphonylation of imines (Scheme V). As a result of the low stability of the products derived from aromatic imines, we performed the reactions in mild homogeneous basic condition by using quinine as a chiral base catalyst giving the α-aryl-α-amido phosphonic acid esters as products (Scheme V, top).6 On the other hand, we performed the addition of dialkyl phosphite to aliphatic imines by using chiral Cinchona alkaloid phase transfer quaternary ammonium salt derivatives using our methodology based on α-amido sulfones (Scheme V, bottom). The results were good for both procedures covering a broad range of α-amino phosphonic acid ester. During the second year Ph.D. studies, I spent six months in the group of Prof. Steven V. Ley, at the Department of Chemistry of the University of Cambridge, in United Kingdom. During this fruitful period I have been involved in a project concerning the enantioselective synthesis of Aspirochlorine. We provided a new route for the synthesis of a key intermediate, reducing the number of steps and increasing the overall yield. Then we introduced a new enantioselective spirocyclisation for the synthesis of a chiral building block for the completion of the synthesis (Scheme VI).