Organocatalytic Reduction of Aromatic Nitro Compounds: The Use of Solid-Supported Phenyl(2-quinolyl)methanol.

The reduction of aromatic nitro compounds has been performed employing a catalytic amount of Wang resin-supported phenyl(2-quinolyl)methanol (Wang-PQM) in the presence of an excess of NaBH to regenerate the reactive reducing species at the end of the process. The reduction products are easily isolated through a simple filtration/extraction protocol, and the catalyst can be efficiently recovered and recycled. The condensation route is generally preferred, and azo- and/or hydrazo-arenes can be easily prepared in high yields.

Bromotrimethylsilane as a selective reagent for the synthesis of bromohydrins.

Bromotrimethylsilane (TMSBr) is a very efficient reagent in the solvent-free conversion of glycerol into bromohydrins, useful intermediates in the production of fine chemicals. As glycerol is a relevant by-product in biodiesel production, TMSBr has been also tested as a mediator in transesterification in acidic conditions, providing FAME from castor oil in good yields, along with bromohydrins from glycerol. Subsequently the glycerol conversion was optimized and depending on the reaction conditions, glycerol can be selectively converted into α-monobromohydrin (1-MBH) or α,γ-dibromohydrin (1,3-DBH) in very good yields.

Synthesis of New Indolizidine Derivatives from 1-(2-Quinolyl)-2-propen-1-ol.

The four-step procedure involving bromination, reduction, and nucleophilic substitution via elimination/addition previously applied to 1-(2-pyridyl)-2-propen-1-ol for the synthesis of indolizidine systems has now been extended to 1-(2-quinolyl)-2-propen-1-ol allowing a general access to benzo-fused derivatives. For instance, (±)-benzo[]lentiginosine has been easily synthesized in an 18% overall yield.

Recent syntheses and biological activity of lentiginosine and its analogues.

(+)-Lentiginosine, a natural trans-1,2-dihydroxyindolizidine belonging to the class of iminosugars, is a potent inhibitor of amyloglucosidase, and a good inhibitor of Hsp90. The non-natural enantiomer, (-)-lentiginosine, induces apoptosis on tumor cells of different origin and is poorly cytotoxic towards non-transformed cells. The significant biological activity of these compounds has resulted in the development of many synthetic approaches for their preparation.

Optimization of N-benzoylindazole derivatives as inhibitors of human neutrophil elastase.

Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease selectivity, and stability compared to our previous leads.

Synthesis of 1,2-dihydroxyindolizidines from 1-(2-pyridyl)-2-propen-1-ol.

1-(2-Pyridyl)-2-propen-1-ol, obtained by vinylation of commercially available picolinaldehyde, resulted a good starting material for the synthesis of the indolizidine skeleton. In particular, a simple process involving bromination, reduction, and nucleophilic substitution (via elimination and addition) allowed an easy conversion of the starting material into (±)-lentiginosine in ~27% overall yield.

Reactivity and synthetic applications of 4,5-dicyanopyridazine: an overview.

Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles.

Domino reactions of 4,5-dicyanopyridazine with dihydroheterocycles: synthetic and mechanistic features.

The title pyridazine 1 was found to react with both 2,3-dihydrofuran (2) and 3,4-dihydro-2H-pyran (9) to give the tetracyclic skeletons 5-8 and the phthalonitrile 12 through the intermediates 4 and 10, respectively. A more complex mechanism was ascertained for the reaction of 1 with the pyrroline 14 which, under suitable conditions, afforded the bicyclic derivative 19 as the predominant product; selective elaborations of this species into the 5,6-dicyanoindoles 22 and 23 are reported.