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International audience; An asymmetric domino Friedel–Crafts/lactonization sequence between phenols and trifluoropyruvatehas been accomplished for the first enantioselective synthesis of (S)-BHFF, a positive allosteric modulator(PAM) of GABAB receptor. The developed protocol leads to 3-OH-benzofuranone derivatives bearing aquaternary stereogenic center, and gives a valuable access to bioactive compounds with promising pharmaceuticalapplications

The reactions of (2-trimethylsilanylmethyl) alpha,beta-unsaturated carboxylic ethyl esters with NsONHCO(2)Et and CaO produce, after treatment with AcOH, alpha-methylene N-(ethoxycarbonyl) beta-amino carboxylic esters through ring opening and elimination of the trimethylsilyl group from the intermediate aziridine. By ozonization and subsequent reductive cleavage these products give the corresponding N-(ethoxycarbonyl) beta-amino alpha-hydroxy esters.

An interpretation is given of a number of observations on the chemiotropic behavior ofBactrocera oleae in connection with olive maceration water and the fly's return to the olive groves after the first summer rains. To this end, the headspace of both maceration water and leaf leaching water, simulating rainfall, were examined. In both cases, the presence of ammonia, which is generally known to attract fruit flies (Diptera, Tephritidae), was detected and, for the first time, in addition to other compounds that are inert for the fly, the presence of styrene was also detected. This aromatic hydrocarbon was found to be a strong attractant. It is shown that both ammonia and styrene are products of the metabolism of microbial flora present on the olive and leaf surface.

"""""""A novel asymmetric nucleophilic epoxidation for R-ylideneoxindole esters has been successfully devised, resulting in enantioenriched spiro compounds with two new contiguous stereocenters. The employed (S)-R,R-diphenylprolinol functions as a bifunctional catalyst, creating a complex H-bond network in conjunction with a substrate and an oxidant"""""""

Substituted cis -1-formyl (or acetyl) bicyclo[3.3.0]octanes are stereospecifically obtained in high yield by a base-catalyzed rearrangement of readily accessible substituted 1-chloro-9-hydrony (or acetoxy) bicyclo[3.3.1] nonanes.

The title compound is the only product in the intramolecular aldol condensation of dione 3 , obtained in turn from the bicyclo[3.3.1]nonanic hydroxyketal 5 . This behaviour is at variance with force field calculations.

Coprostane steroids are selectively oxyfunctionalized at C 5 by dimethyldioxirane and methyltrifluoromethyldioxirane to give useful intermediates for bioactive compounds.

Treatment of endo-2 or exo-2-hydroxy-1-substituted ketals 1a–d with p-toluensulfonic acid in dry benzene results in a reversible C9 bridge cleavage and affords equilibrium mixtures where 2-substituted-6-(1,3-dioxolan-2-yl)cyclooctanones 6a–d are present as main products. Yields in 6a–d are present as the steric hindrance of the substituents at C1 in the substrate increases as well. Deuterium exchange experiments are in favour of an intramolecular 1,3-hydride shift from C2 to C9.

The total synthesis of (±) pinguisone 1, the sterically crowded unusual [5-6] fused-ring sesquiterpene, was accomplished by synthetic elaboration of the 3β,3aβ,7,7aβ-tetramethylbicyclo [4.3.0] non-6-en-1-one 2a prepared by acid catalyzed rearrangement of the easily accessible 1,4β,5,9-tetramethylbicyclo [3.3.1] nonan-9-hydroxy-2-one 3 . This rearrangement constitutes an example of the scarcely observed 1,2 shift of a carbonyl group toward an electron deficient centre.

A new useful synthetic route, to A-nortestosterone via Δ 3(5) A-norsteroids is described.

Phenylselenenyl chloride addition to the 3-exomethylene-1-cepham 1 gave mainly the seleno derivative 2 at room temperature while the dichloro derivative 3 was obtained in refluxing 1,2-dichloroethane. Compounds 2 and 3 transformed into the Δ2 and Δ3 chloromethyl isomer respectively.

All the main fragmentation pathways undergone by trans-4- and trans-2-p-substituted phenylcyclohexanols have been studied, and the ionic abundances have been correlated with the σ constants. This analysis shows that electron withdrawing substituents, increasing the fraction of molecular ions having sufficient energy to decompose, favour all fragmentations. However, along with this ‘non-specific’ substituent effect, there is a ‘specific’ effect, in the opposite sense, increasing the formation of the [M—59]+ and [M—85]+ ions with increasing electron releasing power of the substituents. The loss of water, although it is almost exclusively a 1,4 elimination in the case of trans phenyl cyclohexanols, is not specifically influenced by the substituents.

The methyl 3-methylene-7-phthalimidocepham-4-carnoxylate 3, the corresponding (R)-oxide 2 and the 1,1-dioxide 1 add bromine affording stereoisomeric mixtures of dibromoderivatives. These results are at variance with previous reports regarding 3-exomethylene sulfides and sulfoxides. The stereochemistry of the dibromoderivatives was unambiguously determined via X ray crystallography of 5a, following 1H-NMR correlations. The single dibromo derivatives as well as the isomeric mixtures, can be dehydrobrominated to afford 3-bromomethyl cephem derivatives (7,8,9) in very good yields.

Substituted 2-dichloromethyl-2H-pyrroles, when treated with strong bases under appropriate conditions, undergo ring enlargement giving substituted 3-chloropyridines. The data collected on different substrates and reagents indicate the carbenoid nature of intermediate.

Dehydrations of the anti -ketol 5 and its isomer 10 have been studied. In both cases the 1-hydrindenones 6 and 7 have been almost quantitatively obtained (1:1 ratio) through skeletal rearrangement of the kinetically favoured 9-methylene bicyclononane 9 . This strongly supports the hypothesis of a stepwise rearrangement driven by the relative stabilities of the involved carbonium ions.

The synthesis and the antimicrobial activities of 2,4-diamino-6-(3,4,5-trimethoxybenzyl)pyrimidine (isotrimethoprim) and some related derivatives are reported. The new derivatives have been found scarcely active against bacteria and fungi, with the only exception of 4-chloro-2-methoxypyrimidinyl-3,4,5-trimethoxyphenyldichloromethane, which showed good antibacterial activity against Staphylococcus aureus . Cytotoxicity and antiviral assays, HIV included, have also been determined in comparison with TMP and AZT. Little but selective activity was shown by some derivatives against HIV retrovirus.

The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1 H )-pyrimidinones 1 – 3 undergo highly chemoselective N 1 -methylation or ethylation when treated with methyl- or ethylsulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O 2 -alkylation. Potassium salts of the same bases in DMF undergo prevalent O 2 -attack. Under the same conditions, a similar but less chemoselective behaviour is observed in alkylation of thymine and uracil, where some N 3 -attack occurs. This can be rationalised in terms of the HSAB principle.