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Background Molecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression. Objective The aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy. Study Design/Materials and methods The mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8 mg/Kg body weight). Animals were divided into three groups: G1 (normal tissue), G2 (tumors without treatment), G3 (animals euthanized 48 h after treatment). The photosensitizer used was a chlorin, 5,15-bis-(2-bromo-5-hydroxyphenyl) chlorin in the dose of 8 mg/kg for each animal. Light source of diode laser at a wavelength of 660 nm, fluence rate of 100 mW/cm, and light dose of 100 J/cm was delivery to lesions for treatment. A sample from each animal was investigated by quantitative real time PCR using Rat Apoptosis RT2 Profiler™ PCR Array platform. Results Pro-apoptotic BAK1, CARD6, CASP8, CIDEA, CIDEB, DAPK1, TNF, TNFRSF10B, FASLG, LOC687813, and TP73 genes showed increased expression, and CD40 anti-apoptotic gene showed decreased expression in the group who underwent PDT (G3) in relation to G2. Conclusion The results indicated that these genes are involved more directly with cellular apoptosis induced by PDT using the Chlorin photosensitizer.

A set of 2-galactosylthiazolidine-4-carboxylic acid amides was synthesized with different length for the carbon chain amide moiety. The cytotoxicity of the molecules was evaluated against A375 melanoma and MCF7 breast cancer cell lines. For the derivatives tested, the one that contains a C 16 amide carbon chain is the most active with an IC 50 of 17.0 μM for A375 and 5.8 μM for MCF7. This compound also shows cytotoxicity in the triple negative cancer cell line HCC1806. The selectivity of the compounds was assessed by comparing the cytotoxicity in cancer cell line versus in a fibroblast cell line. Flow cytometry studies show the activation of apoptotic pathways and also DNA damages with blockage of the cell cycle in the S-phase and appearance of peaks in G0/G1-phase.

Ageing of glass RPCs has been extensively studied over the past years. Accompanying the ageing process, two different phenomena were observed: appearance of deposits over the electrode surfaces and structural modification of the glass. In our previous work, using physical–chemical methods and gas chromatography–mass spectrometry techniques, the nature and composition of the surfaces and the structural modification of the glass were established as a mixture of oligomers of Freons. Recently, we performed a direct analysis of glass by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF), avoiding the physical–chemical extraction; the results confirm the nature of the deposit and consequently we focused our investigation on the search for experimental conditions to operate the RPCs to minimize or eliminate the formation of the deposit. The results show that O 2 is an efficient inhibitor of the formation of the deposit and prevents the structural modification of theglass.

The increasing interest in clinical bacterial photodynamic inactivation has led to the search for photosensitizers with higher bactericidal efficiency and less side effects on the surrounding tissues. We present a novel nonionic porphyrin, the 5,10,15-tris(2,6-dichlorophenyl)-20-[4-N-(6-amino-hexyl) sulfonamido)phenyl]-porphyrin (ACS769F4) with substantial improvements in the efficiency of nonionic sensitizers. This porphyrin causes eradication of both Escherichia coli and Staphylococcus aureus by the photodynamic effect but in higher concentrations compared with 5,10,15,20-tetrakis (4-N,N,N- trimethylammoniumphenyl)-porphyrin p-tosylate (TTAP 4+), a known bactericidal tetracationic porphyrin. More important, under such conditions, ACS769F4 proved to be harmless to two mammalian cells lines (human embryonic and baby hamster kidney), causing no reduction in their viability or negative impact on their cytoskeleton, despite its accumulation in cellular structures. On the contrary, TTAP 4+ is shown to accumulate in the nucleus of mammalian cells, in association to DNA, causing chromatin condensation after exposure to light. Furthermore, dark incubation with TTAP 4+ was shown to have a deleterious effect on the microtubule network. Based on its bactericidal efficiency, also observed without exposure to light, and on the low tendency to be harmful or genotoxic to mammalian cells, ACS769F4 should be looked at as an interesting photosensitizer to be evaluated for clinical purposes. A new nonionic porphyrin was synthesized and its properties as antibacterial agent by photodynamic effect were tested against Escherichia coli and Staphylococcus aureus. More relevant, this porphyrin proved to be harmless to two lines of mammalian cells (HEK and BHK cells), causing no reduction in their viability or negative impact on their cytoskeleton, despite its accumulation in cellular structures. On the contrary, a cationic porphyrin with a high efficiency as an antibacterial agent, under the same conditions, was shown to accumulate in the nucleus of mammalian cells, in association to DNA, causing chromatin condensation after exposure to light.

Naphthoquinones undergo 1,3-dipolar cycloaddition with bicyclic munchnones generated from thiazo- lidines affording new pyrrolo-thiazoles with a fused quinone nucleus. The products were obtained as single enantiomers in good yields. These benzo(f)thiazolo(4,3-a)isoindole-6,11(1H,3H)-diones are com- prised of four fused rings and present a very planar structure. The evaluation of their anticancer activity against melanoma A375 and colorectal adenocarcinoma WiDr human cell lines showed only moderate activity but gave insight into the modeling of new structures. (Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.)

Porphyrins with different numbers of β-propionate chains mimicking natural porphyrins were prepared via the 2+2 MacDonald type approach. Photodynamic activity against WiDr colon adenocarcinoma cells showed that activity is related to the number of β-propionate chains, with the derivatives with two carboxylic groups showing higher activity.

Porphyrins and chlorins were generated through dehydrogenation of the corresponding porphyrinogen and bacteriochlorin precursors using activated manganese dioxide and focused microwave irradiation. The application of this inexpensive heterogeneous oxidant under microwave heating conditions, instead of the quinones usually employed in conventional methodologies, allowed short reaction times, simple overall work-ups and good yields.

Improvements over the Rothemund classical reaction methods have allowed the development of capacity to obtain a wide range of structures that were earlier unavailable. Performing the reaction in a mixed nitrobenzene/carboxylic acid medium allowed improvements of yield and purity of the porphyrin obtained, and in some cases the control of the oxidation level of the macrocycle. More recently, novel microwave synthetic methodologies were exploited to achieve important improvements in simple porphyrin chemistry. Tidy sulphonations of simple porphyrins opened the way to diverse desired, inexpensive structures in a very simple manner. The option to concentrate interests on improvements of synthetic methods to obtain simple and diversified tetrapyrrolic structures proved to be advantageous. Interesting biomimetic oxidation and photooxidation systems and PDT sensitizers were developed and significant knowledge was achieved in these specific and related areas. This review presents a view of our own results in the synthetic area, and outlines the contributions therefrom to the study of biomimetic and therapeutic processes.

Tumoral hypoxia is related to severe structural abnormalities of tumor microvessels, leading to deteriorated O2 diffusion. This decreased O2 concentration in cancer cells compromises cellular functions, besides being responsible for resistance to radiation therapy. Consequently, it is very important to know the hypoxic status of a tumor. In this review, the different methodologies available for evaluating cellular hypoxia in vivo are discussed, particularly those in which the hypoxia information is obtained through imaging. Among these the nuclear medicine approach uses ligands to complex with radionuclides. The resulting radioactive complexes which may be single photon or positron emitters, are very useful as imaging probes. The nature of ligands and their corresponding complexes, with application or potential application as hypoxia detectors, will be described. A summary of the most significant results so far obtained in clinical or preclinical applications will also be discussed.

The battle against cancer is so important that all possible weapons must be considered. Photodynamic therapy (PDT) is a therapeutic approach which has proved its capacity to give many excellent results, but it is having some difficulty in being imposed. The simplicity of the mechanism of action of this technique has been compromised by the multidisciplinary approach required for its implementation, which makes its adoption for more general use by health professionals difficult. This review aims to give a perspective of the performance of current approved PDT drugs, and their clinical applications against cancer. Basic investigation in PDT, particularly in the design of new sensitizers, is still ongoing, and needs to be further exploited. Emergent and diversified solutions with excellent results in pre-clinical phases are described to raise the multidisciplinary interest required to boost the clinical use of PDT.

The effective 'one-pot' microwave-assisted synthesis of several substituted 5,10,15,20-tetraarylporphyrins is reported. The microwave-assisted insertion of five different transition metals into the 5,10,15,20-tetraphenylporphyrin, 5,10,15,20-tetrakis(4-chlorophenyl)porphyrin and 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin core was also achieved with high yields. In addition to their simplicity, both these straightforward, experimental protocols were also characterized by extremely short reaction times and quite small quantities of solvents employed.

The ratio, resolution and photophysical characterization of atropisomers of 5,10,15,20-tetrakis(2,6-dichloro-3-N-butylsulfamoylphenyl)porphyrin, 5,10,15,20-tetrakis(2,6-dichloro-3-(N-1-(L)-ethoxycarbonyl-2-methyl-propyl-sulfamoyl)phenyl)porphyrin and 5,10,15,20-tetrakis(2,6-dichloro-3-(N-1-(L)-methoxycarbonyl-3-methyl-butyl-sulfamoyl)phenyl)porphyrin are reported.

The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12h of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10h post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3h, and that of sulfapyridine being 2.1h). In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration.

A series of pyrrolidine-based β-amino alcohols derived from malic acid, citramalic acid and pantolactone with primary amines was prepared and their activity as chiral ligands in the enantioselective alkylation of benzaldehyde using diethylzinc was studied.

Diazafulvenium methides generated from the solution pyrolysis of pyrazolo[1,5-c][1,3]thiazole-2,2-dioxides participate in [8[pi]+2[pi]] cycloadditions giving pyrazolo[1,5-a]pyridine derivatives. 1-Methyl-diazafulvenium, generated under flash vacuum pyrolysis reaction conditions, undergoes an intramolecular sigmatropic [1,8]H shift giving 1-vinyl-1H-pyrazoles. http://www.sciencedirect.com/science/article/B6THS-4HR7298-7/1/af0dd8d679e7977f53bc0d4af9a5b688

Detailed spectral and photophysical properties of 4-halo-5-phenylisoxazoles in cyclohexane solutions are presented, including measurements of energies of lowest excited singlet and triplet states, fluorescence quantum yields, lifetimes, phosphorescence and triplet-singlet difference absorption spectra. Upon addition of ethanol, loss of vibrational structure is observed in fluorescence spectra and attributed to formation of isoxazole-ethanol aggregates. The relevance of these properties to the photochemical and thermal reactivity of these systems is discussed. http://www.sciencedirect.com/science/article/B6TFN-4H16P6W-D/1/aee849eb84047bd4755109fdbbc0c522

Wittig reactions between 10-(phenylsulfonyl)isobornyl (triphenylphosphoranylidene)acetates (1 and 6) and ketenes resulted in asymmetric induction, with the selective synthesis of allenes with axial chirality. Use of the (1R)-(−)-10-(phenylsulfonyl)isoborneol unit allows the synthesis of allenes with S configuration, whereas use of the (1S)-(+)-10-(phenylsulfonyl)isoborneol unit produces allenes with R configuration. The structure of (1R)-(−)-10-(phenylsulfonyl)isobornyl (S)-5,5-dimethylhexa-2,3-dienoate (2e) was determined by X-ray crystallography. Chirooptical studies of the allenic esters were carried out, confirming that two sets of enantiomeric derivatives were obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

3-Carbethoxy-5-phenyl-5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olate was generated from (2R,4R)-N-ethoxyoxalyl-2-phenylthiazolidine-4-carboxylic acid and its reactivity studied. This munchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)-3-phenyl-17H,3H-pyrrolo[1,2-c]thiazole-5,6,7-tricarboxylate could be isolated. The thermolysis of (2R,4R)-N-ethoxyoxalyl-2-phenylthiazolidine-4-carboxylic acid in refluxing acetic anhydride led to the synthesis of N-(1-ethoxycarbonyl-2-phenylvinyl)-2-phenyl-4-thioxo-1,3-thiazolidine. The structure of methyl (2R,4R)-N-ethoxyoxalyl-2-phenylthiazoliddine-4-carboxylate was determined by X-ray crystallography.

Extrusion of sulfur dioxide from pyrrolo[1,2-c]thiazole-2,2-dioxides led to the synthesis of functionalised pyrroles via the generation of 1-azafulvenium methides. Sealed tube reaction conditions allowed the synthesis of N- and C-vinylpyrroles whereas from FVP methyl 1,3-dimethyl-5-oxo-5H-pyrrolizine-2-carboxylate and 4-oxo-1,4-dihydro-1-aza-benzo[f]azulene-3-carboxylates were obtained. These last compounds could also be obtained from the FVP of the N- and C-vinylpyrroles. http://www.sciencedirect.com/science/article/B6THS-4C4DX0X-4/1/eac3571d66ca5b141129aa261f281324

A series of easily obtained pyrrolidine-based -amino alcohols derived from tartaric acid and primary amines was synthesized and used as chiral ligands in the enantioselective alkylation of benzaldehyde. Using diethylzinc, 1-phenyl-1-propanol was obtained with enantiomeric excesses of up to 80% when (3S,4S)-N-(1-naphthylmethyl)-3,4-dihydroxypyrrolidine was used. The nature of the N-substituent on the ligand, as well as the reaction temperature proved to significantly influence reaction product distribution as well as the enantiomeric excess of the chiral alcohol. © 2002 Elsevier Science B.V. All rights reserved.

Intramolecular dipolar cycloaddition of bicyclic münchnones, 5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olates, derived from cyclodehydration of 2-substituted-N-acylthiazolidine-4-carboxylic acids are reported. A range of new pyrrolo[1,2-c]thiazole derivatives (7, 14, 15, 20, 23, and 26) were obtained as single enantiomers from 2-phenylthiazolidines, 2-benzoylthiazolidines, and 2-methylthiazolidine-4-carboxylates. Pyrrolo[1,2-c][1,4]thiazine derivative 27 was also obtained from pyrrolo[1,2-c]thiazole derivative 26. The structures of methyl (2R,4R)-2-(p-methoxybenzoyl)thiazolidine-4-carboxylate (17a), methyl (2R,4R)-2-(p-methoxybenzoyl)-N-(prop-2-ynyloxyacetyl)thiazolidine- 4-carboxylate (18), and 3-oxo-4-phenyl-3,4,6,8-tetrahydro-1H-furo[3',4':2,3]pyrrolo[1,2-c][1,4]thiazine (27) were determined by X-ray crystallography. Chirooptical studies of the pyrrolo[1,2-c]thiazoles were done by confirming the absolute configuration at the chiral center C-3.

Phenylacetaldehyde (PhA) has been observed as a by-product in H2O2 metalloporphyrin catalytic oxidation of styrene. We have found that the mechanism of these oxidations depends on the relative amount of the carboxylic acid that is used as co-catalyst. With an excess of the organic acid less PhA is formed due to the intervention of metalloacylperoxo species (1) instead of a metallo-oxo species (2). Whatever the conditions used, the PhA which is formed comes chiefly from styrene oxide (SO) isomerization. This process seems to be due to the presence of oxygen centered radicals formed through metalloporphyrin reaction with hydrogen peroxide.

The thermolysis of haloazidoalkenes and 2-halo-2H-azirines is described. 2-Benzoyl-2-halo-2H-azirine-3-carboxylates (2a and 2b) underwent ring expansion leading to the synthesis of new 4-haloisoxazoles in high yield. The same isoxazoles were also obtained in high yield directly from haloazidoalkenes (la and 1b). The thermolysis of the β-azido-α,β-unsaturated ketone 1e led to complete conversion to form the corresponding isoxazole 4e. An isoxazole derivative 4c could also he obtained, in moderate yield, from 2-bromo-3-phenyl-2H-azirine-2-carhoxylate (1c). From the thermolysis of azidoalkene Id the only product that could be isolated was pyrazine-2,3,5,6-tetracarboxylate (5).

Oxygen activation using an aldehyde as a sacrificial reductant and mediated by metalloporphyrins is a radical process with a variable induction period in which the macrocycle function is to generate the acyl radicals to initiate a chain mechanism. This function can be also efficiently promoted by simple metal salts, which leads to a very simple and practical oxidative system that is able to epoxidize alkenes in good yields.

Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated. The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac-β-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity.

Manganese complexes of 5,15-diaryl-beta-substituted-porphyrins were prepared and their behaviour as oxidation catalysts was studied. The role of the pyrrolic and meso-substituents on the activity and selectivity of these catalysts was studied to reveal new structure-activity relationships in these porphyrin-based epoxidation catalysts. The beneficial effect of the halogen atoms at the meso-phenyls is still observed with these catalysts but, for the first time, a strong dependence on the selectivity of the epoxide production was found to be dependent on the nature of the non-halogen substituents at the beta-pyrrolic positions of the porphyrin. Copyright © 2001 John Wiley & Sons, Ltd.

Chlorins have been synthesized through the reduction of the corresponding porphyrins although theoretically they can be obtained from reduced macrocycle forms as porphyrinogens. A new method for the oxidation of meso-tetraarylporphyrinogens was developed generating a substantial amount of chlorin relatively to porphyrin. The structure of the porphyrinogen, particularly the presence of substituents on the meso-phenyl groups, is decisive for the final yield of chlorin. In the case of meso-tetrakis(2,6-dichlorophenyl)porphyrinogen, 92% of the corresponding chlorin is obtained.

Nucleophilic substitution reactions of 2-halo-2H-azirine with potassium phthalimide and aniline allowed the preparation of new substituted 2H-azirines. The reactions of 2-bromo-3-phenyl-2H-azirine-2-carboxylate with methylamine led to the synthesis of a-diimines and from the reaction with water, a 3-oxazoline was obtained. # 2000 Published by Elsevier Science Ltd.

The metalloporphyrin catalytic oxidation of hydrocarbons using dilute hydrogen peroxide as oxygen donor with a two-phase system in the presence of an excess of benzoic acid is studied. Porphyrins derived from meso-tetrakis(2,6-dichlorophenyl)porphyrin and bearing sulfonamide substituents at β or meso positions and halogens at β positions were used. The system allowed for very efficient catalytic epoxidations and hydroxylations of hydrocarbons. It is proved that the excess of benzoic acid is critical to the catalyst efficiency and stability. The role of the lipophilic acid in this system is discussed.

Four porphyrins and one chlorin having aromatic groups at the meso position have been synthesized and tested as potential sensitizers for the photooxidation of phenols. The yields of conversion of 1,5-dihydroxynaphthalene and 2,3,5-trimethylphenol to their corresponding quinones have been determined following photolysis in air-saturated acetonitrile–dichloromethane solutions in the presence of these compounds, and are higher than those obtained using other photosensitizers. The reactions are shown to proceed via formation of singlet oxygen (1Δg), followed by its addition to the phenol. A mechanism is presented. Rates of reaction of singlet oxygen with the substrates were determined by studying the decay of the 1O2* emission. Singlet oxygen quantum yields and formation efficiencies for the photosensitizers have been determined by laser flash photolysis and photoacoustic calorimetry. In addition, for two of the porphyrins, these were also measured using time-resolved luminescence. In all cases, highly efficient singlet oxygen formation is observed. The stabilities of the sensitizers to prolonged photolysis were studied. The compound 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin was found to be a particularly efficient photosensitizer for oxidation of phenols. It is suggested that this is due both to its high singlet oxygen yield and to its good photostability.

New chiral dithioether compounds (–)-1-benzyl-3,4-bis(methylsulfanyl)pyrrolidine (–)-degusme, (–)-1-benzyl-3,4-bis(isopropylsulfanyl)pyrrolidine (–)-deguspri and (+)-1-benzyl-3,4-bis(phenylsulfanyl)pyrrolidine (+)-degusph were prepared from (+)-L-tartaric acid. The addition of the dithioether compounds to a dichloromethane solution of [Ir(cod)2]BF4 afforded the chiral cationic complexes [Ir(cod){(–)-degusme}]BF4 1 [Ir(cod){(–)-deguspri}]BF4·CH2Cl2 2 and [Ir(cod){(+)-degusph}]BF4 3. The dithioether ligands were replaced by PPh3 in complexes 1, 2 and 3 providing the [Ir(cod)(PPh3)2]BF4 complex. The addition of H2 to 1, 2 and 3 at –70 °C gave cis-dihydridoiridium(III) complexes [IrH2(cod)L]BF4 [L = (–)-degusme 4, (–)-deguspri 5 or (+)-degusph 6]. The relative stability of possible isomers for complexes 1–6 was studied by molecular mechanics calculations. Complexes 1–3 were active precursors in the asymmetric hydrogenation of different prochiral dehydroamino acid derivatives and itaconic acid, at room temperature under atmospheric pressure of H2, and the highest enantiomeric excess obtained was 68%.

Several families of photosensitizers are currently being scrutinized for antimicrobial photodynamic therapy applications. Differences in physical and photochemical properties can lead to different localization patterns as well as differences in singlet oxygen production and decay when the photosensitizers are taken up by bacterial cells. We have examined the production and fate of singlet oxygen in Escherichia coli upon photosensitization with three structurally-different cationic photosensitizers, namely New Methylene Blue N (NMB), a member of the phenothiazine family, ACS268, a hydrophobic porphyrin with a single cationic alkyl chain, and zinc(II)-tetramethyltetrapyridinoporphyrazinium salt, a phthalocyanine-like photosensitizer with four positive charges on the macrocycle core. The kinetics of singlet oxygen production and decay indicate different localization for the three photosensitizers, whereby NMB appears to localize in an aqueous-like microenvironment, whereas ACS268 localizes in an oxygen-shielded site, highly reactive towards singlet oxygen. The tetracationic zinc(II) tetrapyridinoporphyrazine is extensively aggregated in the bacteria and fails to produce any detectable singlet oxygen.

Work during the last decade laid down the basis for biomimetic oxidation catalysis, which has become an established technique. Preliminary work relied on the use of metal complexes of 5,10,15,20-tetrakisphenylporphyrin (TPP), but these proved to be inadequate to perform the catalytic function. Further, derivatives of TPP with suitable and adequately positioned substituents, allowed the preparation of high performance catalysts, in terms of catalytic efficiency and stability, for some selected oxidations under specific reaction conditions and for a diversity of oxygen donors. The first oxidations were achieved using the ‘special’ oxygen donor iodosylbenzene, but cheaper and generally available oxidants such as sodium hypochlorite or hydrogen peroxide are presently used as the oxidants. Catalysts capable of promoting stereoselective catalysis are reported. Conditions for the efficient use of the catalysts so far reported require particular specificities and the catalytic activity is only shown, in the majority of the reported works, in the presence of selected species to act as axial ligands to the metal ion of the catalyst. Specific porphyrin structures were reported where the addition of a specific axial ligand can be avoided.

The 2-azadiene 5 was generated from the Schiff bases of serine methyl ester and cysteine methyl ester and 2-allyloxybenzaldehyde 1 . Compound 5 failed to undergo an intramolecular Diels-Alder reaction. When it was generated in the presence of aluminium trichloride the pyridine 6a was isolated; the structure of this pyridine indicates that the catalyst has reversed the regiochemistry of the dimersiation of 5 . The reaction of the activated allyloxybenzaldehyde 2 with cysteine methyl ester follows a different course from that of 1. The allylic function is transferred to sulfur and the Schiff base 9 is formed. This undergoes a rapid internal 13-dipolar cycloaddition at room temperature to give the thienopyrrole 10 the structure of which has been established by X-ray crystallography.

2H-Azirine-3-carboxylates unsubstituted at C-2 act as dipolarophiles in the reaction with diazomethane giving new 4,5-dihydro-3H-pyrazole derivatives. The synthesis of a pyrimidine was also achieved via 1,3-dipolar cycloaddition of methyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate with an azomethine ylide. http://www.sciencedirect.com/science/article/B6THS-493P1M1-17/1/5df1370edad7138f3cae89fadd9b5c4d

In this communication we describe the first results of an efficient synthesis of [beta]-free-dipyrromethanes in water. This new method affords very pure products in moderate to high yields, using a cheap, non-toxic, environment friendly solvent, in a one-step procedure from pyrrole and carbonyl compounds, needing little or no work up procedures. http://www.sciencedirect.com/science/article/B6THS-48FBYP9-W/1/58e27991754d6f7646fd28ad555927b4

The aim of this work was to synthesize an ester prodrug of diclofenac and β-cyclodextrin suitable for colonic delivery. The synthesis of an ester linkage between diclofenac and β-cyclodextrin was conducted by the nucleophilic substitution of mono-6-tosyl-β-cyclodextrin under microwaves irradiation. After purification, the conjugate was characterized by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry; infrared (IR) spectroscopy; proton nuclear magnetic resonance ((1)H NMR) spectroscopy; and two-dimensional rotating frame nuclear overhauser effect (ROESY) spectroscopy. The purity was qualified by high pressure liquid chromatography (HPLC). To assess its potential for colonic delivery, the conjugate was evaluated for stability in simulated gastric and small intestinal fluids, and in fecal material from humans processed within a slurry under anaerobic conditions. The conjugate was successfully synthesized with a yield of 20% following purification. The mass spectra showed the parent peak m/z 1434 corresponding to [conjugate+Na] adduct. IR and NMR results confirmed that the carboxyl group of diclofenac is covalently bound to one of the hydroxyl groups of cyclodextrin by an ester linkage. Moreover, ROESY data indicated that the formation of the conjugate is not accompanied by the inclusion of diclofenac within the cyclodextrin. The conjugate was otherwise stable in simulated gastric and small intestinal conditions, but was also readily hydrolyzed liberating diclofenac in less than 2h within the human fecal slurry. This confirmed the potential for this new prodrug as a carrier for colonic delivery.

The Diels-Alder reactions of N-benzylidenedehydroalanine methyl ester 1a with but-3-en-2-one and with other electron deficient dienophiles have been found to give new dihydro- and tetrahydropyridines. The cycloaddition reactions are regioselective but not stereoselective. Cycloaddition reactions between 1a and enamines have also been observed. The [4 + 2] cycloaddition reactions of other N-arylidenedehydroalanine methyl esters are also reported. Two new types of azadiene were prepared, namely N-(benzoylmethylene)dehydroalanine methyl ester 1e and N-(ethoxycarbonylmethylene)dehydroalanine methyl ester 1f. Their reactions with N-cyclohexen-1-ylpyrrolidine and with N-cyclopenten-1-ylpyrrolidine have led to the isolation of the dihydropyridine and pyridine esters.

The Diels-Alder reaction of 1,2,4-triazines with cyclic vinyl ethers leads to a range of substituted pyridines with hydroxyalkyl and oxoalkyl side chains. With dihydrofuran the aromatization of the 1:1 adduct is inhibited by conformational factors and this allows 2:1 adducts to be isolated. Different regioselectivity is observed in the 2:1 adducts formed from ethyl 5-phenyl-1,2,4-triazine-3-carboxylate 1f and from ethyl 5,6-diphenyl-1,2,4-triazine-3-carboxylate 1b. An X-ray crystal structure of the 2:1 adduct 5 formed from 2,3-dihydrofuran and 1b is reported.

The thiazolidines 2 , derived from L-cysteine methyl ester and aromatic aldehydes, react with silver carbonate and DBU to give methyl 2-(arylideneamino)acrylates 1 .these 2-azadienes undergo Diels-Alder reactions with both electron rich dienophiles and electron deficient dienophiles.

Naphthoquinones undergo 1,3-dipolar cycloaddition with bicyclic mnchnones generated from thiazolidines affording new pyrrolo-thiazoles with a fused quinone nucleus.

Porphyrinogens, generated in solution by condensation of aldehydes with pyrrole can be carefully oxidized to a mixture of chlorins (III) and prophyrins (IV).

α-Oxophosphonium ylides (3a–3e) react with N-chlorosuccinimide and N-bromosuccinimide in the presence of azidotrimethylsilane giving the corresponding haloazidoalkenes (4a–4g) with elimination of triphenylphosphine oxide. These compounds were completely converted to the 2H-azirines 5a–5g on heating in heptane.

(2R,4R)-N-Acyl-2-phenylthiazolidine-4-carboxylic acids were used to generate 5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olates with internal dipolarophiles. The intramolecular 1,3-dipolar cycloaddition of these mesoionic species led to the synthesis of new 1H-pyrrolo[1,2-c]thiazole derivatives (8a, 8b and 12) as single enantiomers. The structure of 8a was determined by X-ray crystallography.