Stereoselectivity of Additions to N-Methyl Acetonitrilium Fluorosulfonate

Alkoxy-N-methyl-acetiminium salts were prepared by addition of CH3OH and C2H5OH to N-methyl acetonitrilium fluorosulfonate at low temperature. Analysis of the (5)J(HH) and (3)J(13)C-H coupling constants in the NMR spectra showed an anti addition with a diastereoselectivity of >9596. Deprotonation of these salts with (Z)-configuration gave the corresponding N-methyl-alkoxyacetimines with very high (E)-configuration. Upon protonation at -78 degrees C, these iminoesters gave the corresponding alkoxy-N-methyl-acetirninium salts with (E)-configuration. Computational analyses of the iminoesters and the corresponding iminium cations including the conformations give insight into the relative stability. Nitrilium salts can be used as reagents, exemplified by some esterifications between simple acids and alcohols.

Low-lying excited states and nonradiative processes of 9-methyl-2-aminopurine

he UV spectrum of the adenine analogue 9-methyl-2-aminopurine (9M-2AP) is investigated with one- and two-color resonant two-photon ionization spectroscopy at 0.3 and 0.05 cm−1 resolution in a supersonic jet. The electronic origin at 32 252 cm−1 exhibits methyl torsional subbands that originate from the 0A′′1 (l = 0) and 1E ″ (l = ±1) torsional levels. These and further torsional bands that appear up to 000+230 cm−1 allow to fit the threefold (V 3) barriers of the torsional potentials as ∣∣V′′3∣∣=50 cm−1 in the S 0 and ∣∣V′3∣∣=126 cm−1 in the S 1 state. Using the B3LYP density functional and correlated approximate second-order coupled cluster CC2 methods, the methyl orientation is calculated to be symmetric relative to the 2AP plane in both states, with barriers of V′′3=20 cm−1 and V′3=115 cm−1. The 000 rotational band contour is 75% in-plane (a/b) polarized, characteristic for a dominantly long-axis 1ππ* excitation. The residual 25% c-axis polarization may indicate coupling of the 1ππ* to the close-lying 1 nπ* state, calculated at 4.00 and 4.01 eV with the CC2 method. However, the CC2 calculated 1 nπ oscillator strength is only 6% of that of the 1ππ* transition. The 1ππ* vibronic spectrum is very complex, showing about 40 bands within the lowest 500 cm−1. The methyl torsion and the low-frequency out-of-plane ν′1 and ν′2 vibrations are strongly coupled in the 1ππ* state. This gives rise to many torsion-vibration combination bands built on out-of-plane fundamentals, which are without precedence in the 1ππ* spectrum of 9H-2-aminopurine [S. Lobsiger, R. K. Sinha, M. Trachsel, and S. Leutwyler, J. Chem. Phys.134, 114307 (2011)]. From the Lorentzian broadening needed to fit the 000 contour of 9M-2AP, the 1ππ* lifetime is τ ⩾ 120 ps, reflecting a rapid nonradiative transition.

Effect of synthetic agonists of toll-like receptor 9 on canine lymphocyte proliferation and cytokine production in vitro.

Synthetic agonists of TLR9 containing novel DNA structures and R'pG (wherein R=1-(2'-deoxy-beta-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine) motifs, referred to as immune modulatory oligonucleotides (IMOs), have been shown to stimulate T(H)-1-type-immune responses and potently reverse allergen-induced T(H)-2 responses to T(H)-1 responses in vitro and in vivo in mice. In order to investigate the immunomodulatory potential of IMOs in dogs, canine peripheral blood mononuclear cells (PBMC) from healthy dogs were stimulated with three different IMOs and a control IMO, alone or in combination with concanavalin A (ConA). Lipopolysaccharide (LPS) was used as a positive control for B lymphocyte activation. Carboxyfluorescein diacetate succinimidyl ester and phenotype staining was used to tag proliferating T and B lymphocytes (CD5(+) and CD21(+)) by flow cytometry. Real-time PCR and ELISA were processed to assay cytokine production of IFN-gamma, IL-10, TGF-beta, IL-6 and IL-10. Like LPS, IMOs alone induced neither proliferation of CD5(+) T cells nor CD21(+) B cells, but both LPS and IMO had the capacity to co-stimulate ConA and induced proliferation of B cells. In combination with ConA, one of the IMOs (IMO1) also induced proliferation of T cells. IMO1 also significantly enhanced the expression of IFN-gamma on the mRNA and protein level in canine PBMC, whereas expression of IL-10, TGF-beta and IL-4 mRNAs was not induced by any of the IMOs. These results indicate that in canine PBMC from healthy dogs, IMO1 was able to induce a T(H)-1 immune response including T- and B-cell proliferation.

Osteo-odonto-keratoprosthesis (OOKP) and the testing of three different adhesives for bonding bovine teeth with optical poly-(methyl methacrylate) (PMMA) cylinder.

AIM Preparation of the lamina during osteo-odonto-keratoprosthesis (OOKP) design is complex, and its longevity and watertightness important. To date, only acrylic bone cements have been used for bonding the optical cylinder to the tooth dentine. Our aim was to evaluate different dental adhesives for OOKP preparation. METHODS Specimens of bovine teeth were produced by preparing 1.5-mm thick dentine slices with holes having a diameter of 3.5 mm. Each group (n=10 per group) was luted with either classic poly-(methyl methacrylate) (PMMA) bone cement, universal resin cement or glass ionomer cement. All specimens underwent force measurement using a uniaxial traction machine. RESULTS The highest mean force required to break the bond was measured for PMMA bone cement (128.2 N) followed by universal resin cement (127.9 N), with no statistically significant difference. Glass ionomer cement showed significantly lower force resistance (78.1 N). CONCLUSIONS Excellent bonding strength combined with easy application was found for universal resin cement, and thus, it is a potential alternative to acrylic bone cement in OOKP preparation.

On the Methyl-Transfer Reaction in Crystalline Methyl 2-(Methylthio)benzenesulfonate: a Thermally Induced Non-Topochemical Solid-State Reaction

The rearrangement of methyl 2-(methylthio)benzenesulfonate (1) to the zwitterionic 2-(dimethyl-sulfonium)benzenesulfonate (2) is known to proceed in solution by intermolecular Me transfers. The same rearrangement has been observed to occur in crystalline 1, but the crystal structure shows that the molecular packing is not conducive to intermolecular Me transfer. The reaction has been carried out with mixed crystals composed of 1 and deuteriomethylated (D6)-l. By fast-atom-bombardment mass spectroscopy, it has been shown that the product consists of a 1:2:1 mixture of the non-, tri-, and hexadeuterated species, the mixture expected, if the solid-state reaction proceeds by intermolecular Me transfers. From this result, together with the slower rates of conversion in the single crystal compared with the melt, it can be concluded that the reaction must occur not topochemically but rather at defects such as microcavities, surfaces, and other irregularities in the ordered crystal arrangement.

Chemistry of pyrrocorphins: methylative opening of the macrocycle between rings A and D, a side reaction in the peripheral C-methylation of a 20-methyl-pyrrocorphinate

One of the minor products from the previously described peripheral -methylation of a magnesium()-20-methyl--pyrrocorphinate is a C-19-methylated 19,20-seco-corphinoid derivative which, on complexation with nickel() acetate, recyclizes to a nickel()-tetradehydro-corrinate.

Chemistry of pyrrocorphins: synthesis of isobacteriochlorins and pyrrocorphins bearing a methyl group at the meso position between rings A and D

A sigmatropic methyl shift from the angular position C-1 in ring to the position C-20 between rings and constitutes the crucial step in syntheses leading to a 20-methyl-isobacteriochlorin and to 20-methyl-pyrrocorphins which served as substrates in the investigation presented in the accompanying communication.

Two enzymes responsible for the formation of herbivore-induced volatiles of maize, the methyltransferase AAMT1 and the terpene synthase TPS23, are regulated by a similar signal transduction pathway

Herbivore-induced volatiles play an important role in the indirect defense of plants. After herbivore damage, volatiles are released from the plant and can attract herbivore enemies that protect the plant from additional damage. The herbivore-induced volatile blend is complex and usually consists of mono- and sesquiterpenes, aromatic compounds, and indole. Although these classes of compounds are generally produced at different times after herbivore damage, the release of the terpene (E)-β-caryophyllene and the aromatic ester methyl anthranilate appear to be tightly coordinated. We have studied the herbivore induction patterns of two terpene synthases from Zea mays L. (Poaceae), TPS23 and TPS10, as well as S-adenosyl-L-methionine:anthranilic acid carboxyl methyltransferases (AAMT1), which are critical for the production of terpenes and anthranilate compounds, respectively. The transcript levels of tps23 and aamt1 displayed the same kinetics after damage by the larvae of Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae), and showed the same organ-specific and haplotype-specific expression patterns. Despite its close functional relation to TPS23, the terpene synthase TPS10 is not expressed in roots and does not display the haplotype-specific expression pattern. The results indicate that the same JA-mediated signaling cascade maycontrol the production of both the terpene (E)-β-caryophyllene and aromatic ester methyl anthranilate.

Role of Methyl Salicylate on Oviposition Deterrence in Arabidopsis thaliana

Plants attacked by herbivores have evolved different strategies that fend off their enemies. Insect eggs deposited on leaves have been shown to inhibit further oviposition through visual or chemical cues. In some plant species, the volatile methyl salicylate (MeSA) repels gravid insects but whether it plays the same role in the model species Arabidopsis thaliana is currently unknown. Here we showed that Pieris brassicae butterflies laid fewer eggs on Arabidopsis plants that were next to a MeSA dispenser or on plants with constitutively high MeSA emission than on control plants. Surprisingly, the MeSA biosynthesis mutant bsmt1-1 treated with egg extract was still repellent to butterflies when compared to untreated bsmt1-1. Moreover, the expression of BSMT1 was not enhanced by egg extract treatment but was induced by herbivory. Altogether, these results provide evidence that the deterring activity of eggs on gravid butterflies is independent of MeSA emission in Arabidopsis, and that MeSA might rather serve as a deterrent in plants challenged by feeding larvae.

Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea-induced photoreceptor degeneration.

PURPOSE: To identify programmed cell death (PCD) pathways involved in N-methyl-N-nitrosourea (MNU)-induced photoreceptor (PR) degeneration. METHODS: Adult C57BL/6 mice received a single MNU i.p. injection (60 mg/kg bodyweight), and were observed over a period of 7 days. Degeneration was visualized by H&E overview staining and electron microscopy. PR cell death was measured by quantifying TUNEL-positive cells in the outer nuclear layer (ONL). Activity measurements of key PCD enzymes (calpain, caspases) were used to identify the involved cell death pathways. Furthermore, the expression level of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), key players in endoplasmic reticulum (ER) stress-induced apoptosis, was analyzed using quantitative real-time PCR. RESULTS: A decrease in ONL thickness and the appearance of apoptotic PR nuclei could be detected beginning 3 days post-injection (PI). This was accompanied by an increase of TUNEL-positive cells. Significant upregulation of activated caspases (3, 9, 12) was found at different time periods after MNU injection. Additionally, several other players of nonconventional PCD pathways were also upregulated. Consequently, calpain activity increased in the ONL, with a maximum on day 7 PI and an upregulation of CHOP and GRP78 expression beginning on day 1 PI was found. CONCLUSIONS: The data indicate that regular apoptosis is the major cause of MNU-induced PR cell death. However, alternative PCD pathways, including ER stress and calpain activation, are also involved. Knowledge about the mechanisms involved in this mouse model of PR degeneration could facilitate the design of putative combinatory therapeutic approaches.

Total Synthesis of Aignopsanes, A Class of Sesquiterpenes: (+)-Aignopsanoic Acid A, (−)-Methyl Aignopsanoate A, and (−)-Isoaignopsanoic A

A general strategy for the synthesis of aignopsanes, a new family of sesquiterpene natural products of marine origin, is presented. The total synthesis of (+)-aignopsanoic acid A (1), (−)-methyl aignopsanoate A (2), and (−)-isoaignopsanoic A (3) has been achieved and their absolute configuration confirmed. (+)-Microcionin-1 (4), a structurally related furanosesquiterpene isolated in both enantiomeric forms from marine sponges, was also synthesized and its absolute configuration established in an unambiguous way. Interestingly, we report that (+)-microcionin-1 (4), can be converted by a simple oxidation process to aignopsanoic acid A (1). This transformation supports the hypothesis that (+)-microcionin-1 (4) may be an intermediate in the biosynthesis of aignopsanes.

Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus

INTRODUCTION Daylight-mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe. OBJECTIVES To establish consensus recommendations for the use of daylight photodynamic therapy (DL-PDT) using topical methyl aminolaevulinate (MAL) in European patients with AKs. METHODS The DL-PDT consensus recommendations were developed on behalf of the European Society for Photodynamic Therapy in Dermatology and comprised of 10 dermatologists from different European countries with experience in how to treat AK patients with PDT. Consensus was developed based on literature review and experience of the experts in the treatment of AK using DL-PDT. RESULTS The recommendations arising from this panel of experts provide general guidance on the use of DL-PDT as a dermatological procedure with specific guidance regarding patient selection, therapeutic indications, when to treat, pre-treatment skin preparation, MAL application and daylight exposure for patients with AK in different countries of Europe. CONCLUSIONS This consensus recommendation provides a framework for physicians to perform DL-PDT with MAL cream while ensuring efficiency and safety in the treatment of patients with AK in different European countries.