Search

The use of aminals in dynamic covalent chemistry is slightly underexplored, probably due to their inherent instability. Here we report the spontaneous [2+2] macrocyclization of tetrakis(aminals). Their unexpected stability and structural modularity, the dynamic nature of the connections and their water tolerance make them appealing systems for future applications as stimulus-responsive materials.

Pyrazine-decorated benzotriazole cores allow the orthogonal combination of two dipolar systems within a single molecule. A series of this type of derivatives was synthesized and their photophysical features were studied. The properties of these compounds showed remarkable differences in function depending on the substitution in the pyrazine ring of the benzotriazole core. Furthermore, the two-photon absorption property (2PA) was studied to determine the structure-properties relationship for the reported compounds. The best dye achieved a crosssection of 1532 GM, which was higher than values previously obtained for similar D-π-A-π-D benzotriazole derivatives. TD-DFT calculations, which supported the experimental observations, indicating the interaction between the two dipolar systems was responsible for enhancing the 2 PA properties and favoring bathochromic shifts. PCI2019-111825-2, PID2019-104293GB-I00, UMA18-FEDERJA-007, SBPLY/17/180501/000189, PID2020-119636GB-I00 , RED2018-102331-T, Universidad de Málaga / CBUA

A series of donor-π-acceptor-π-donor (D-π-A-π-D) benzoazole dyes with 2H-benzo[d][1,2,3]triazole or BTD cores have been prepared and their photophysical properties characterized. The properties of these compounds display remarkable differences, mainly as a result of the electron-donor substituent. Dyes with the best properties have visible-light absorption over λ=400 nm, large Stokes shifts in the range of about 3500-6400 cm-1 , and good fluorescence emission with quantum yields of up to 0.78. The two-photon absorption properties were also studied to establish the relationship between structure and properties in the different compounds synthesized. These results provided cross sections of up to 1500 GM, with a predominance of S2 ←S0 transitions and a high charge-transfer character. Time-dependent DFT calculations supported the experimental results.

Herein, we present an easy and efficient synthesis of amino terminal dendrons, combining protection/deprotection reactions with copper-catalyzed azide alkyne cycloaddition in a convergent way. This new approach affords dendrons in gram scale with excellent yields and easy purification. By choosing the appropriate azido-functionalized core, these dendrons lead to a more efficient and controlled convergent synthesis of dendrimers with different sizes and shapes and multivalence. The amino terminal dendrimers were analyzed by diffusion-ordered spectroscopy experiments. The observed dendrimer size is in excellent correlation with the expected size and shape by molecular dynamic simulations. The construction of these kinds of nanostructures, in a simple and efficient way, opens new opportunities for biomedical applications. Moreover, by choosing the appropriate core, these versatile macromolecules become an excellent fluorescent biomarker.

The detection of reactive oxygen species (ROS) in biological systems and its imaging is of great importance. Among them, the hydroxyl radical ( OH) stands out as one of the most reactive, playing an important role in many physiological and pathological processes. Here we report a two-photon (TP) turn-on fluorescent probe with good selectivity and sensitivity towards OH. The molecular design of this naphthalene-indoline compound enables it to accurately target lysosomes in its non-fluorescent (“off”) state, where interaction with OH gives rise to the fluorescent (“on”) state and allows for the imaging of OH generation in living mouse embryonic fibroblast (MEF) cells. The present study provides an approach for improving our understanding of the role of OH in biological processes.

We report the synthesis and comprehensive study of two chromophores based on 4H-pyranylidene moiety as a part of the π-conjugated spacer. Triphenylamine (TPA) acts as donor and tricarbonitrile-based electron-accepting groups complete these V-shaped D–A–D architectures (A, acceptor; D, donor). Their electrochemical, photophysical and nonlinear optical properties are analyzed in detail by using a joint experimental and theoretical approach. The two chromophores exhibit near-infrared fluorescence, large Stokes shift, enhanced emission in tetrahydrofuran/water mixtures and good photostability. Additionally, the dimerization of triphenylamine groups to tetraphenylbenzidine (TPB) takes place upon electrochemical and chemical oxidation showing their peculiar electrochemical behavior and film formation capabilities. Interestingly, high molecular first hyperpolarizabilities and two-photon absorption cross-sections were found, highlighting their potential applications in electro-optical devices. Overall, our work demonstrates that these near-infrared (NIR) fluorescent chromophores are versatile materials with a myriad of applications ranging from optoelectronics to biological applications., The work at the University of Málaga was funded by the MICINN (PID2019-110305GB-I00, PID2019-104293GB-I00, RTI2018-095410-B-I00, EuroNanoMed 2019 PCI2019-111825-2), the Institute of Health Carlos III (ISCIII) RETIC ARADYAL (RD16/0006/0012) and by the Junta de Andalucıa (P09-FQM-4708, UMA18-FEDERJA-080, UMA18-FEDERJA-007, PIER-0084-2019). The work at the University of Zaragoza was funded by the MICINN (PID2019-104307GB-I00/AEI/10.13039/501100011033) and Gobierno de Aragón (E47_20R). The work at the University of Stuttgart was funded by the German Science Foundation (DFG) through the project “LU 1445/7-1, project number 416982273” on electrooptical hybrid modulators, C. Malacrida is acknowledged for discussions. S. G.-V. thanks the MINECO for a FPU predoctoral fellowship (FPU17/04908) and CB-M for FPU fellowship (FPU16/02516). Computer resources, technical expertise and assistance provided by the SCBI (Supercomputing and Bioinformatics) centre of the University of Málaga are gratefully acknowledged. We thank the Vibrational spectroscopy lab (EVI) of the Research Central Services (SCAI) of the University of Málaga and John Pearson (BIONAND) for help with laser confocal microscopy analysis. We gratefully acknowledge the ICTS “NANBIOSIS” facilities, more specifically the U28 Unit of the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND), for their help with the 2PA characterization and the microscopy studies.

The combination of two two-photon-induced processes in a Förster resonance energy transfer (FRET)-operated photochromic fluorene-dithienylethene dyad lays the foundation for the observation of a quartic dependence of the fluorescence signal on the excitation light intensity. While this photophysical behavior is predicted for a four-photon absorbing dye, the herein proposed approach opens the way to use two-photon absorbing dyes, reaching the same performance. Hence, the spatial resolution limit, being a critical parameter for applications in fluorescence imaging or data storage with common two-photon absorbing dyes, is dramatically improved.

Novel pH probes based on 2-(6-methoxynaphthalen-2-yl)-3,3-dimethyl-3H-indole have been synthesized and characterized. These compounds display excellent "off-on" fluorescence responses to acidic pH especially under two-photon (TP) excitation conditions as well as strong selectivity and sensitivity toward H

Bis(dioxaborine) dyes of the A-π-A format (A: acceptor, π: conjugated bridge) were prepared and photophysically characterized. The best performing dyes feature (a) visible-light absorption (>400 nm), (b) high molar absorption coefficients (up to 70000 m-1 cm-1 ), (c) Stokes shifts in the range of ca. 2500-5800 cm-1 , and (d) strong fluorescence emission with quantum yields of up to 0.74. This yields very bright-emitting dyes for one-photon excitation. However, the most intriguing feature of the dyes is their strong two-photon absorption. This was achieved by means of increased π-conjugation in the phenylene or phenylene-thiophene bridges through the variation of the conjugation length and rigidity. This provided two-photon absorption cross sections of up to 2800 GM (1 Goeppert-Mayer (GM)=10-50 cm4 s photon-1 ). Considering the mentioned high fluorescence quantum yields, exceptionally bright-emitting A-π-A two-photon absorbing dyes with low molecular mass are obtained. Time-dependent density-functional theory calculations corroborated the experimental results.

12 p.-6 fig.-1 graf. abst., BACKGROUND: Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin-CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis., METHODS: Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD-I (N-protein, 3-oxopropanamide) and AD-II (N-protein, 3-aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches., RESULTS: Two synthetic analogs of AD-I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV-treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls., CONCLUSION: We have identified AD-I as one CLV antigenic determinant, which is the drug fragment that remains protein-bound., The present study has been supported by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): PI12/02529, PI15/01206, CP15/00103, RETICs RIRAAF RD12/0013/0001, RD12/0013/0003 and RD12/0013/0008, RETIC ARADYAL RD16/0006/0001, RD16/0006/0012 and RD16/0006/0021, Biobank Network RD09/0076/00112, and Biobank platform PT13/0010/0006) and by State Secretariat for Research, Development and Innovation of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF), “Una manera de hacer Europa”: MINECO SAF2012-36519, SAF2015-68590R, CTQ2013-41339P, and CTQ2016-75870P). Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by European Regional Development Fund (ERDF), “Andalucía se mueve con Europa”: CTS-06603); Andalusian Regional Ministry Health (grants: PI-0699-2011, PI-0159-2013, PI-0179-2014, PI-0241-2016, and PI-0250-2016), Merck-Serono Research Grant from Fundación Salud 2000 and “Premio UNICAJA a la innovación en biomedicina y salud.” CM holds a “Nicolas Monardes” research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. MIM holds a “Miguel Servet I” and GB holds a “Rio Hortega,” both research contracts by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Social Fund (ESF)): CP15/00103 and CM16/00067. TDF hold a “Ramon y Cajal” research contract from Ministry of Economy and Competitiveness (RYC-2013-13138).

Mesenchymal stem cells (MSCs) are promising candidates for a range of tissue regeneration applications. Adequate scaffolds are necessary for their application in vivo, where interactions between cells and the surface material are critical. Arginine-glycine-aspartic acid tripeptides (RGD) were conjugated to polyamidoamine (PAMAM) dendrimers and used to pre-treat test surfaces. We demonstrate that pre-treatment with dendrimer-presented tripeptides efficiently increases MSC adhesion to a polystyrene test surface, and that treatment effectiveness is related to how tripeptides are presented by the dendrimer to the cell. We tested both R-G-D–dendrimer and dendrimer–R-G-D arrangements and found the former to be optimal in terms of surface adhesion.

Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy. Yes

In vitro drug allergy tests have limited sensitivity, partly due to a poor understanding of the immunological recognition of in vitro drug-protein conjugates. We have designed and synthesized multivalent mono- and bi-epitope dendrimeric antigen (DeAn) conjugates and studied their chemical and tridimensional structures. We describe differences in the spatial distribution and conformation of these conjugated epitopes for the first time: a partially hidden benzylpenicilloyl and a more exposed amoxicilloyl. Our data suggest that DeAn conjugates provide a useful model for studying IgE recognition in patients who suffer from an allergic reaction to benzylpenicillin and/or amoxicillin. 1D and 2D NMR, MDS and immunochemical studies provide evidence that both antigen composition and tridimensional distribution play key roles in IgE-antigen recognition. Bi-epitope DeAn conjugates could potentially allow the diagnosis of patients allergic to any of these two drugs with a single test and represent the basis for a broadly-applicable in vitro assay. From the clinical editor: The prevalence of allergic drug reactions is rising and there is an imperative need to identify patients at risk. In this interesting and important article, the authors developed a novel method for detecting drug specific IgE antibodies, responsible for allergic reactions, by using multivalent mono- and bi-epitope Dendrimeric Antigen (DeAn) conjugates. The continued success of this research may pave way of eventual development of a simple diagnostic test.

Over recent years the importance of dendrimers has continued to increase in both life and material sciences. Multiple chemical strategies have been described toward the preparation of dendrimeric structures. Here, we present a new approach for the production of all-aliphatic polyamide dendrimers. In our approach, iterative 3,3′-diaminopivalic acid connections act as building blocks for dendrimer construction. 3,3′-Diazidopivalic acid units underpin a two-step pathway involving carboxylic acid–amine condensation, followed by azide reduction. The carboxylic acid–amine condensation step can be carried out by conventional methods, while the hydrogen-catalyzed azide-to-amine reduction is a clean process particularly appropriate for dendrimer preparation. Spectroscopic characterization of functionalized surface azides (Gn-N3) and amines (Gn-NH2) confirm the proposed structures. These dendrimers were studied in explicit solvent by atomistic forcefield-based molecular dynamics to characterize structural properties such as shape, radius and monomer distribution. Our results show that these compounds are similar in size and shape, with Gn-NH2 having a slightly bigger size and exhibiting lower terminal unit backfolding.

Neutral water-soluble aza-dipyrromethene boron difluoride (aza-BODIPY) derivatives are synthesized for biological imaging applications. Aqueous solubility is increased by optimizing the synthetic conditions to obtain aza-BODIPYs with several tetraethyleneglycol groups. Their spectral properties and assays performed on cultured cells, demonstrate the potential of these compounds as near-infrared (NIR) emitting fluorescent probes.

Aminonaphthalimide-BODIPY energy transfer cassettes were found to show very fast (kEET ≈ 10(10)-10(11) s(-1) and efficient BODIPY fluorescence sensitization. This was observed upon one- and two-photon excitation, which extends the application range of the investigated bichromophoric dyads in terms of accessible excitation wavelengths. In comparison with the direct excitation of the BODIPY chromophore, the two-photon absorption cross-section δ of the dyads is significantly incremented by the presence of the aminonaphthalimide donor [δ ≈ 10 GM for the BODIPY versus 19-26 GM in the dyad at λ(exc)=840 nm; 1 GM (Goeppert-Mayer unit)=10(-50) cm(4) smolecule(-1) photon-(1)]. The electronic decoupling of the donor and acceptor, which is a precondition for the energy transfercassette concept, was demonstrated by time-dependent density functional theory calculations. The applicability of the new probes in the one- and twophoton excitation mode was demonstrated in a proof-of-principle approach in the fluorescence imaging of HeLa cells. To the best of our knowledge, this is the first demonstration of the merging of multiphoton excitation with the energy transfer cassette concept for a BODIPY-containing dyad.

A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups was synthesized. The synthesis was carried out using a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD) involving the direct condensation of 3,3′-diazidopivalic acid as a building block. Iterative azide reduction/amide formation increases the dendrimer generation. The BAPAD dendrimer was designed with a cystamine core. Reduction of the disulfide bond allows the incorporation of BAPAD dendrons into a 1,8-naphthalimide functionalized with a maleimide group. The fluorescence properties of DeAn were studied in PBS and compared with the properties of an equivalent dendron possessing amino-terminal groups. Both molecules shown high fluorescence quantum yields in PBS and could readily be visualized by fluorescence microscopy. DeAn was used as a synthetic antigen in a biomedical assay that tests their potential as an amoxicillin carrier in drug internalization by dendritic cells (DC) from tolerant and allergic patients. Cytometry data suggest that the dendrons are non-toxic and easily internalized by DCs, while confocal microscopy images indicate that the compounds are preferentially accumulated in the cytoplasm. These results indicate that BAPAD dendrons are good candidates for synthetic scaffolds for biomedical applications.

Seven tetra-coordinate organoboron fluorophores with hetero-biaryl N,O or N,N chelate ligands were prepared and photophysically characterized (in toluene). The electronic variation of the heteroaromatic moiety provided a means for the fine-tuning of the UV/vis-absorption and emission spectra. In the most interesting cases the spectra were re-shifted to maximum absorb-ance at wavelengths longer than 500 nm and emission maxima between 620 and 660 nm. The pronounced intramolecular charge-transfer character of the dyes yielded large Stokes shifts (3500–5100 cm–1), while maintaining appreciable fluorescence quantum yields of up to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the dyes enabled their application as stains of vesicle substructures in confocal fluorescence microscopy imaging., The funding by the Spanish Ministry of Economy and Competitiveness (Grants CTQ2014-54729-C2-1-P for U.P., CTQ2013-48164-C2-1-P, CTQ2013-48164-C2-2-P for A.R., CTQ2013-41339-P and CTQ2015-71896-REDT for E.P.I., Ramon y Cajal contract RYC-2013-12585 for A.R.), the European Union (FEDER), and the Andalusian Government (Grants 2012/FQM-2140 for U.P., 2009/FQM-4537 and 2012/FQM-1078 for A.R., postdoctoral contract for V.F.P.) is acknowledged. Furthermore, we are thankful for the provided access to the Supercomputing and Bioinformatics Center (University of Malaga).

A series of synthetic benzylpenicillinoylated dendrimers has been prepared using up to 4th generation PAMAM dendrimers. These nanoconjugates, as nanosized Dendritic Antigens, are useful in the diagnostic evaluation of drug allergy due to specific molecular recognition with the Human Immunological System (IgE). The morphology and dimensions of the conjugates coupled to the orientation of the peripheral benzylpenicillin residues in the dendrimers may play key roles in such molecular recognition processes. Herein, the characterization and conformation of these structures are studied by a detailed analysis of 1D (1H and 13C NMR) and 2D NMR (1H,1H-NOESY) spectra. These dendrimers in explicit solvent were studied by the atomistic forcefield-based molecular dynamics. Structural properties such as shape, radius-of-gyration and distribution of the monomers will be discussed in relation to the experimental observations.

A general study on the conjugate addition of anionic nucleophiles to alkylidene bis(sulfoxides) is presented. Alkoxides gave high yielding and diastereoselective addition reactions, which could be influenced by solvents and the counteranion. Azides provided an interesting entry into sulfinyl-substituted triazoles. Organometallics, mainly copper reagents, proved also to be valuable nucleophiles, and complete inversion of the stereoselectivity was achieved in the addition reaction with the latter. Modelizations provide a rationale for the observed diastereoselectivity.

Six strongly fluorescent four-coordinate organoboron N,C chelates containing an aryl isoquinoline skeleton were prepared. Remarkably, the fluorescence quantum yields reach values of up to 0.74 in oxygen-free toluene. The strong B-N interaction was corroborated by the single-crystal X-ray analysis of two dyes. The intramolecular charge-transfer character of the fluorophores was evidenced by solvatochromism studies and time-dependent DFT calculations at the PCM(toluene)/CAM-B3LYP/6-311++G(2d,p)//PCM(toluene)/B3LYP/6-311G(2d,p) level of theory. The compounds combine high chemical stability with high photostability, especially when equipped with electron-donating substituents. The strong fluorescence and the large Stokes shifts predestine these compounds for use in confocal fluorescence microscopy. This was demonstrated for the imaging of the N13 mouse microglial cell line. Moreover, significant two-photon absorption cross sections (up to 61 GM) allow the use of excitation wavelengths in the near-infrared region (>800 nm), The financial support by the Spanish MINECO (CTQ2014-54729-C2-1-P for U.P., CTQ2013-48164-C2-1-P, CTQ2013-48164-C2-2-P for A.R., CTQ2013-41339-P for E.P.I., FPU fellowship for R.L-R., Ramon y Cajal contract RYC-2013-12585 for A.R.), the European Union (FEDER), and the Junta de Andalucia (2012/FQM-2140 for U.P., 2009/FQM-4537, 2012/FQM-1078 for A.R., postdoctoral contract for V.F.P.) is acknowledged. We are grateful for the access to the Supercomputing and Bioinformatics Center (University of Malaga) and the provided technical support. Tristan Neumann (exchange student from the University of Kiel, Germany) performed preliminary experiments.

We report a flexible approach to the total synthesis of 4,5-dioxoaporphines based on the palladium(0) catalyzed Suzuki cross-coupling of phenylboronic acids with sterically hindered 2-bromo phenyl acetates or bromo phenyl acetamides, followed by sequential bicyclization of biarylacetamides promoted by oxalyl chloride/Lewis acid. The reduction of 4,5-dioxoaporphines provides a chemoselective entry to aporphines, dehydroaporphines and 4-hydroxy-dehydroaporphines. A three-steps total synthesis for (±)-O,O′-dimethylapomorphine from readily accessible precursors is also reported.

The amounts of sinoacutine, glaucine and protopine were used to identify three phytochemical groups from the six known populations of Platycapnos saxicola Willk. A combination of GC/MS and 1 H-NMR have been used for the identification and quantitation of

The isoquinoline alkaloids protopine, cryptopine, sinactine, stylopine, bicuculline, adlumine, parfumine, fumariline, fumarophycine, fumaritine, dihydrofumariline, parfumidine and dihydrosanguinarine have been determined and identified by gas chromatography-mass spectrometry in Fumaria agraria, F. bastardii, F. capreolata, F. sepium, F. densiflora, F. faurei, F. officinalis subsp. officinalis, F. parviflora, F. petteri subsp. calcarata and F. macrosepala. The chemotaxonomic significance of the results is discussed.

In continuation of our chemical studies on the Andalusian Flora (Valpuesta et al., 1995, 1999; Suau et al., 1998, 2002), we focused on the genus Senecio in our search for pyrrolizidine alkaloids (PAs). We collected three endemic species, viz. Senecio elodes Boiss. ex DC. (MGC 25920) and S. granatensis Boiss. (MGC 20646) from Sierra Nevada (Granada, Spain), and S. malacitanus L. (MGC 30068) from El Pantano del Agujero (Malaga, Spain). Voucher specimens are deposited at the Herbarium of the Department of Botany of the University of Malaga (MGC).

Double cyclization of aryloxy-phenyl acetamides is promoted by oxalyl chloride/stannyl chloride and gives 3,4-dioxocularine and aristocularine alkaloids. Rearrangement of the dibenzoxepine ring prior to the second cyclization produces xanthene derivatives. The synthesized cularinoids exhibit significant activity against various tumoral cell lines.

We describe herein a new synthesis of enantiopure alkylidene 1,1-bis-p-tolyl-sulfoxides (5), based on a two-steps sequence. The first one involves the alkylation of the lithium anion of the (S,S)-bis-p-tolylsulfinylmethane (1) with aldehydes. The second one consists in a mild dehydration of the sulfinyl alcohols 3 and 4 with the morpho CDI reagent. Some features (reactivity, diastereoselectivity) of the alkylation reaction are discussed.

Linear 2,3-di-n-alkoxy-azapolycyclic arenes are shown to act as potent gelators for a variety of organic liquids. This outstanding property is restricted to molecules that have no nitrogen atoms on the 1,4 positions. The readily accessible 5,12-diazatetracenes form thermoreversible gels which do not involve hydrogen bonding and open up new prospects for larger scale applications. Their gel-forming abilities and colouration can be sligthly tuned by variation in acidic conditions.

The Polonovski–Potier reaction of trans and cis berbines N-oxides was studied. The 8-cyano derivative obtained from transN-oxides were used to synthesize 8-hydroxymethyl and 8-methyl berbines. This procedure was applied to the stereocontroled synthesis of (8R, 14S)-(−)-8-methylcanadine from (14S)-(−)-canadine.

The direct insertion of a hydroxymethyl group at position C-8 in a protoberberinium ion by photoaddition of methanol was approached via two mechanistic pathways: acetone-sensitized and single-electron transfer. The latter produces 8-hydroxymethylberbines in good yields after reduction. By combining this photochemical reaction with the oxidation of the photoproduct, syntheses of (±)-solidaline and its C-13 epimer from palmatine chloride were accomplished for the first time. On the other hand, insertion of a hydroxymethyl group at position 14 of the berberine skeleton in order to open a synthetic pathway for zijinlongine proved unsuccessful.

Sixteen isoquinoline alkaloids were isolated from Berberis vulgaris subsp. australis . In addition to quaternary protoberberines and bisbenzylisoquinolines, a new seco - bis benzylisoquinoline, (-)-tejedine, is reported.

International audience; The chemistry of bis(sulfoxides) is discussed from two starting materials, (Ss,Ss)-bis-p-tolylsulfinylmethane and (Ss,Ss)-bis-p-tolylsulfinyl alkylidenes. Reactions presented include Michael additions, ionic-radical crossover processes and coordination complexes formations.

The synthesis of two 7-glycosyl-6-thiotheophylline nucleosides where the sugar moieties are β-D-glucose (1b) and α-D-arabinose (2b) is reported. The syn-anti equilibrium of the peracetyl derivatives was studied by the line-shape and the 1H-NMR nOe methods, and molecular mechanics analysis.

The introduction of a hydroxymethyl group at the C-8 position of berberinium salts was readily achieved by photoaddition of methanol. The resulting photoproducts were isolated as tetrahydroprotoberberine derivatives. By combining this photochemical reaction with the oxidation of the photoproduct, the synthesis of (±)-solidaline starting from palmatine chloride was accomplished for the first time.

The plants of genus Fumaria L., which encompasses about 40 species (Southon and Buckingham, 1989), are annual herbs which have a wide distribution from India to Macaronesia. Twenty-two species are restricted to the Ibero-Mauritanian Region, which includes Algeria, Morocco and Spain (Liden, 1986). Plant material of Fumaria agraria Lag. (Fumariaceae) was collected from Churriana (Malaga, Spain) and that of Fumaria sepium Boiss. (Fumariaceae) from Los Barrios (Cadiz, Spain). Both were identified by the Department of Botany of the Faculty of Sciences of the University of Malaga. Voucher specimens (F. agraria MGC-23062 and, F. sepium MGC-31528) are deposited in the Faculty’s herbarium.

The introduction of a hydroxymethyl group at the C-8 position of berberinium salts was readily achieved by photoaddition of methanol. The resulting photoproducts were isolated as tetrahydroprotoberberine derivatives. By combining this photochemical reaction with the oxidation of the photoproduct, the synthesis of (±)-solidaline starting from palmatine chloride was accomplished for the first time.

The direct insertion of a hydroxymethyl group at position C-8 in a protoberberinium ion by photoaddition of methanol was approached via two mechanistic pathways: acetone-sensitized and single-electron transfer. The latter produces 8-hydroxymethylberbines in good yields after reduction. By combining this photochemical reaction with the oxidation of the photoproduct, syntheses of (±)-solidaline and its C-13 epimer from palmatine chloride were accomplished for the first time. On the other hand, insertion of a hydroxymethyl group at position 14 of the berberine skeleton in order to open a synthetic pathway for zijinlongine proved unsuccessful.

We describe herein a new synthesis of enantiopure alkylidene 1,1-bis-p-tolyl-sulfoxides (5), based on a two-steps sequence. The first one involves the alkylation of the lithium anion of the (S,S)-bis-p-tolylsulfinylmethane (1) with aldehydes. The second one consists in a mild dehydration of the sulfinyl alcohols 3 and 4 with the morpho CDI reagent. Some features (reactivity, diastereoselectivity) of the alkylation reaction are discussed.

Enantiopure cyclic allylic alcohols were obtained from cyclic ketones and bis-sulfoxides through a domino reaction mixing anionic and concerted elementary steps. Total transfer of chirality was achieved, presumably through cooperative effects of both sulfoxides units. Depending on the ring size, both sulfinyl groups could be converted, giving C 2 -symmetric bis-allylic alcohols.