Pd-H from Pd/C and triethylamine: Implications in palladium catalysed reactions involving amines

The palladium hydride-iminium complex generated from Pd/C and triethylamine catalyses the isomerisation of allylic alcohols into carbonyl compounds, and Pd/C catalyses the conjugate reduction of activated double bonds using triethylamine as the source of the two newly incorporated hydrogen atoms via the same complex.     

Reductive complexation of cycloheptatrienes by iron pentacarbonyl and catalytic sodium borohydride

Fe(CO)5 and a catalytic amount of sodium borohydride react with cycloheptatrienes in protic solvents to yield the corresponding tricarbonyl(eta 4-1,3-diene)iron complexes in a one-pot procedure, which has been found to be particularly efficient for the synthesis of the useful tricarbonyl(cyclo-heptadiene)iron complex.     

N-heterocyclic carbene-catalyzed Michael additions of 1,3-dicarbonyl compounds

A study of the organocatalytic activity of N‐heterocyclic carbenes (NHCs) in the Michael addition of 1,3‐dicarbonyl compounds has allowed us to identify 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (IPr) as an excellent catalyst for this transformation (up to 99 % yield with a 2.5 mol % catalyst loading), and the reaction was found to be of broad scope. Two early applications of this unprecedented catalytic activity of NHCs are described, that is, the domino carbocyclization reactions of simple cyclic 1,3‐dicarbonyl and malonic acid derivatives, which allow stereoselective access to bridged bicyclic compounds, and the stereoselective synthesis of cyclohexanols (or cyclohexene). Early mechanistic investigations are also reported.     

Chiral resolution by crystallization of host-guest supramolecular complexes

The crystallization behaviour and the physical characterization of supramolecular complexes formed between permethylated-α-cyclodextrin (TMα-CD) and the enantiomers of phenylethanol (PE) are investigated. According to crystal structure analyses, complexes containing the pure guest enantiomers are almost isomorphous, indicating that the host presents a poor ability to distinguish PE enantiomers at a molecular level. Nevertheless, crystallizations from racemic PE in water induce an efficient chiral discrimination and allow the enantio-separation of the guests despite the existence of a solid solution revealed by XRPD and coupled TG-DSC analyses. The enantiodifferentiation is explained by solubility differences between the two diastereomeric complexes in the studied temperature range. Moreover, it is shown that the diastereomeric complex TMα-CD/(S)-PE crystallizes in two distinct phases: a monohydrate and an anhydrous form, with a transition temperature close to 37°C. The insertion of a water molecule in the crystals grown below 37°C does not involve any other change of the crystal packing nor of the molecular conformation, but leads to different crystal growth mechanisms inducing different morphologies and distinct thermal behaviours. This revised version was published online in July 2006 with corrections to the Cover Date.     

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases

Voltage-gated Na⁺ (Na_V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na_V channel ligands. With the objective of discovering new blockers of Na_V channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na_V channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC₅₀. These five alkaloids were then assayed using the Na⁺ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNa_V1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na⁺ currents elicited by the hNa_V1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na⁺ currents elicited by the hNav1.2 and hNav1.6 channels, with IC₅₀ values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block Na_V channels, with promising therapeutical applications.     

Peptide synthesis in room temperature ionic liquids

We demonstrate that chemical peptide coupling using modern coupling agents is efficient in rt ionic liquids. This new approach presents some advantages, especially in the case of hindered amino acids, which are not easy to couple under standard conditions, since high purities for the crude peptides were observed with respect to coupling in classical solvents.     

New approach to bicyclo[5.3.0]decanes: stereoselective guaiane synthesis

[reaction: see text] A conceptually new and highly versatile approach to bicyclo[5.3.0]decanes, based on dichloroketene cycloaddition-diazoalkane ring expansion, is disclosed, and its relevance to natural product synthesis is demonstrated through the preparation of three guaiane sesquiterpenes. A concise total synthesis of a guaian-8,12-olide, 6-deoxygeigerin, highlights the effectiveness of the new methodology.