Diisothiocyanates as heterodienophiles or dipolarophiles in the presence of α‐thioxothioamides or mesoionic thiazoles

Reactions of α‐thioxothioamides ( 1 ) with diisothiocyanates were carried out in the hope of generating the N,N′‐bis(1,3‐thiazoline‐2‐thiones) ( A ). Although that purpose could not be achieved, we succeeded in preparing the monocycloadducts 7 from the phenylene‐1,2‐diisothiocyanate ( 4 ). The benzimidazole derivatives 8 and 9 were also characterized and a mechanism was assumed to account for this intramolecular process. On the other hand, the regioselective synthesis of the N,N′‐biimidazole ( 13 ) containing the phenylene bridge was performed by the treatment of the 5‐aminothiazolium chloride ( 2 ) with the diisothiocyanate ( 4 ) in a basic medium. The mesoionic derivative 13 probably arises from the monoimidazolium‐4‐thiolate ( 12 ) which was shown to react with the salt 2 under similar conditions to give the primary cycloadduct 14 as an intermediate towards the bis(imidazolium) ( 13 ). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:617–624, 2001     

Addition of isocyanides to α‐(methylthio)‐benzylidenamidinium iodides: A surprising access to 2‐(dialkylamino)imidazoles and 3,5‐diamino‐2H‐pyrrolium salts

A number of 2‐(dialkylamino)‐5‐(methylthio)imidazoles 2 are obtained by treating the formamidinium iodides 1a,b with isocyanides R³ NC under mild conditions. Reduction of these species can occur in the reaction medium to furnish the corresponding imidazoles 3 . In some cases, double cycloaddition across the imine bond of starting salts 1 also provides the (azetidin‐1‐yl‐methylene)ammonium iodides 4 . Reactions with tert‐butyl and isopropyl isocyanides in refluxing acetonitrile convert the acetamidinium iodide 1c into the 3,5‐diamino‐2H‐pyrrolium salts 7 . Mechanisms are suggested to account for these ring‐closure processes. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:370–376, 2000     

Ferrocene and Porphyrin Monolayers on Si(100) Surfaces: Preparation and Effect of Linker Length on Electron Transfer

The missing link : Ferrocene and porphyrin monolayers are tethered on silicon surfaces with short (see picture, left) or long (right) linkers. Electron transfer to the silicon substrate is faster for monolayers with a short linker.

     

A new biolistic intradermal injector

We present a novel intradermal needle-free drug delivery device which exploits the unsteady high-speed flow produced by a miniature shock tube to entrain drug or vaccine particles onto a skin target. A first clinical study of pain and physiological response of human subjects study is presented, comparing the new injector to intramuscular needle injection. This clinical study, performed according to established pain assessment protocols, demonstrated that every single subject felt noticeably less pain with the needle-free injector than with the needle injection. Regarding local tolerance and skin reaction, bleeding was observed on all volunteers after needle injection, but on none of the subjects following powder injection. An assessment of the pharmacodynamics, via blood pressure, of pure captopril powder using the new device on spontaneously hypertensive rats was also performed. It was found that every animal tested with the needle-free injector exhibited the expected pharmacodynamic response following captopril injection. Finally, the new injector was used to study the delivery of an inactivated influenza vaccine in mice. The needle-free device induced serum antibody response to the influenza vaccine that was comparable to that of subcutaneous needle injection, but without requiring the use of an adjuvant. Although no effort was made to optimize the formulation or the injection parameters in the present study, the novel injector demonstrates great promise for the rapid, safe and painless intradermal delivery of systemic drugs and vaccines.     

12‐ to 22‐Membered Bridged β‐Lactams as Potential Penicillin‐Binding Protein Inhibitors

As potential inhibitors of penicillin‐binding proteins (PBPs), we focused our research on the synthesis of non‐traditional 1,3‐bridged β‐lactams embedded into macrocycles. We synthesized 12‐ to 22‐membered bicyclic β‐lactams by the ring‐closing metathesis (RCM) of bis‐ω‐alkenyl‐3(S)‐aminoazetidinone precursors. The reactivity of 1,3‐bridged β‐lactams was estimated by the determination of the energy barrier of a concerted nucleophilic attack and lactam ring‐opening process by using ab initio calculations. The results predicted that 16‐membered cycles should be more reactive. Biochemical evaluations against R39 DD‐peptidase and two resistant PBPs, namely, PBP2a and PBP5, revealed the inhibition effect of compound 4d , which featured a 16‐membered bridge and the N‐tert‐butyloxycarbonyl chain at the C3 position of the β‐lactam ring. Surprisingly, the corresponding bicycle, 12d , with the PhOCH₂CO side chain at C3 was inactive. Reaction models of the R39 active site gave a new insight into the geometric requirements of the conformation of potential ligands and their steric hindrance; this could help in the design of new compounds.     

Synthesis,alkali metal picrate extraction,and alkali metal cation binding selectivities of some new cage‐annulated polyoxamacrocyclic crown ethers

Five new cage‐annulated crown ethers, i.e., 4a, 4b, 6b, 11a, and 11b, have been synthesized and their respective alkali metal picrate extraction profiles along with that of a previously synthesized host molecule, 6a, have been obtained. These results are compared with the corresponding results obtained for electrospray ionization mass spectrometric (ESI‐MS) measurements of relative binding selectivities displayed by the same hosts toward a series of alkali metal chlorides. Among the crown‐5 hosts studied, 6a displays enhanced avidity toward complexation with K⁺ picrate in liquid‐liquid extraction experiments. Among the three crown‐6 hosts, 4b proved to be the best alkali metal picrate extractant and displayed significant levels of avidity toward complexation with the larger alkali metal cations (i.e., K⁺, Rb⁺, and Cs⁺). The trends in the picrate extraction and the ESI‐MS results obtained herein show several notable similarities and some differences. The similarities generally stem from size‐selective binding properties that are intrinsic to the different cavity sizes of the cage‐annulated macrocycles, whereas the differences reflect the important influence of solvation effects on the binding properties of the macrocycles.     

Basic Substances,a Sustainable Tool to Complement and Eventually Replace Synthetic Pesticides in the Management of Pre and Postharvest Diseases: Reviewed Instructions for Users

Synthetic pesticides are widely used to protect crops from pathogens and pests, especially for fruits and vegetables, and this may lead to the presence of residues on fresh produce. Improving the sustainability of agriculture and, at the same time, reducing the adverse effects of synthetic pesticides on human health requires effective alternatives that improve the productivity while maintaining the food quality and safety. Moreover, retailers increasingly request fresh produce with the amounts of pesticides largely below the official maximum residue levels. Basic substances are relatively novel compounds that can be used in plant protection without neurotoxic or immune-toxic effects and are still poorly known by phytosanitary consultants (plant doctors), researchers, growers, consumers, and decision makers. The focus of this review is to provide updated information about 24 basic substances currently approved in the EU and to summarize in a single document their properties and instructions for users. Most of these substances have a fungicidal activity (calcium hydroxide, chitosan, chitosan hydrochloride, Equisetum arvense L., hydrogen peroxide, lecithins, cow milk, mustard seed powder, Salix spp., sunflower oil, sodium chloride, sodium hydrogen carbonate, Urtica spp., vinegar, and whey). Considering the increasing requests from consumers of fruits and vegetables for high quality with no or a reduced amount of pesticide residues, basic substances can complement and, at times, replace the application of synthetic pesticides with benefits for users and for consumers. Large-scale trials are important to design the best dosage and strategies for the application of basic substances against pathogens and pests in different growing environments and contexts.     

Spectres de vibration de composes organiques des elements de la colonne IVB : VIII. Derives organometalliques a liaison germanium—azote: Trialkylgermyl-et bis(trialkylgermyl)-amines

We have examined in the 3600–100 cm^?1 region the IR and Raman spectra of three bis(trialkylgermyl)amines (R₃Ge)₂NR′ (R = Me, Et; R′ = H, C₆H₅), of three dialkyl(trialkylgermyl)amines R₃GeNR′₂ (R = Me, Et; R′ = Me, n-Bu) and of two triethylgermylpyrazoles:

Assignments are discussed for the characteristic vibrations of these derivatives.     

Nouvelle methode de decarbomethoxylation

Heterocycles substituted by two carbomethoxy groups on the same carbon lose one of these groups when reacted with piperidine. This reaction has been extended to substituted malonic and cyanacetic esters. The mechanism of this reaction is discussed. Piperidine also causes the decarboxylation of substituted malonic and cyanacetic acids.