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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 title reaction affords enantioenriched spiro compounds (II) and (III) with two contiguous stereocenters.

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

New potentially bioactive α-spiroaziridino-γ- and -δ-lactams have been prepared by treatment of α-methylene-γ- and -δ-lactams with ethyl N-{[(4-nitrophenyl)sulfonyl]oxy}carbamate (NsONHCO2Et) in the presence of CaO. These compounds, through reductive aziridine ring opening, can be intermediates for the synthesis of α- and β-aminolactams, which are useful as conformational constraints in peptides. The above procedure has been successfully extended to one α-methyleneoxindole to obtain a new spirooxindole derivative, a potential precursor of natural alkaloids. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Oxiranyl ring opening of trans-stilbene oxide gave rise to anti- or syn-2-bromo-1,2-diphenylethanols, using either MgBr(2).Et(2)O or MgBr(2).Et(2)O, NaBr, and KBr with Amberlyst 15, respectively. Starting from optically pure (R,R)-trans-stilbene oxide, (1R,2R)- and (1R,2S)-2-amino-1,2-diphenylethanols were obtained in high yield and ee.

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.

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.

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.

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 of 2, 4-diamino-6-(3, 4, 5-trimethoxybenzyl)pyrimidine (isotrimethoprim) has been accomplished starting from 2-(O-methyl)-6-(3, 4, 5-trimethoxybenzyl)uracil by standard procedures. The benzyluracil derivative has been obtained by reacting O-methylisourea sulphate and ethyl 3, 4, 5-trimethoxyphenacetylace-tate.