Roger Dommisse

Selective palladium-catalyzed aminations on dichloropyridines

Abstract Palladium-catalyzed amination proved to be a valuable strategy for the selective introduction of aromatic and heteroaromatic amines, including aminopyridines and aminodiazines, on dichloropyridines. The use of mild amination conditions resulted in maximum selectivity and excellent base sensitive functional group tolerance.

Structural analysis of phenolic glucosides from salicaceae by NMR spectroscopy

Abstract Some characteristic features of the NMR spectra of phenolic glycosides are described in order to facilitate the structural determination of these compounds.

1H NMR based metabolomics of CSF and blood serum: A metabolic profile for a transgenic rat model of Huntington disease

Huntington disease (HD) is a hereditary brain disease. Although the causative gene has been found, the exact mechanisms of the pathogenesis are still unknown. Recent investigations point to metabolic and energetic dysfunctions in HD neurons. Both univariate and multivariate analyses were used to compare proton nuclear magnetic resonance spectra of serum and cerebrospinal fluid (CSF) taken from presymptomatic HD transgenic rats and their wild-type littermates. N-acetylaspartate (NAA), was found to be significantly decreased in the serum of HD rats compared to wild-type littermates. Moreover, in the serum their levels of glutamine, succinic acid, glucose and lactate are significantly increased as well. An increased concentration of lactate and glucose is also found in CSF. There is a 1:1 stoichiometry coupling glucose utilization and glutamate cycling. The observed increase in the glutamine concentration, which indicates a shutdown in the neuronal-glial glutamate-glutamine cycling, results therefore in an increased glucose concentration. The elevated succinic acid concentration might be due to an inhibition of succinate dehydrogenase, an enzyme linked to the mitochondrial respiratory chain and TCA cycle. Moreover, reduced levels of NAA may reflect an impairment of mitochondrial energy production. In addition, the observed difference in lactate supports a deficiency of oxidative energy metabolism in rats transgenic for HD as well. The observed metabolic alterations seem to be more profound in serum than in CSF in presymptomatic rats. All findings suggest that even in presymptomatic rats, a defect in energy metabolism is already apparent. These results support the hypothesis of mitochondrial energy dysfunction in HD.

3′,4-Di-O-methylcedrusin: synthesis, resolution and absolute configuration

The title compound has been synthesised in racemic form by a biomimetic reaction sequence. The two enantiomers were resolved by column chromatography of one of the synthetic intermediates. On the basis of CD results a tentative absolute configuration for the synthetic enantiomers and natural 3′,4-di-O-methylcedresin is proposed.

The first tandem double palladium-catalyzed aminations: synthesis of dipyrido[1,2-a∶3′,2′-d]imidazole and its benzo- and aza-analogues

A new strategy for the synthesis of the title compounds via a regio- and chemoselective one-pot inter- and intramolecular Buchwald-Hartwig amination of 2-chloro-3-iodopyridine with aminoazines and -diazines is reported.

Suzuki reactions on chloropyridazinones: an easy approach towards arylated 3(2H)-pyridazinones

Abstract The synthesis of 4-aryl-5-methoxy-, 5-aryl-4-methoxy- and 4,5-diaryl-3(2H)-pyridazinones via Suzuki palladium-catalysed cross-coupling reactions with the corresponding chloro-3(2H)-pyridazinones is described.

Proton relaxation enhancement by means of serum albumin and poly-l-lysine labeled with DTPA-Gd3+: Relaxivities as a function of molecular weight and conjugation efficiency

A series of poly-L-lysine chains, with molecular weight ranging from 3300 up to 102,000 Da, were labeled with DTPA-Gd3+. No significant differences in longitudinal and transversal relaxivity, could be demonstrated as a function of the chain length. The R1 and R2 relaxivities were respectively 2.5 and 5 times superior to those of plain DTPA-Gd3+ (at 2.4 T). Bovine serum albumin was also labeled in a way that a wide (DTPA-Gd3+)/BSA range (3-39) was obtained. The longitudinal relaxivity, of these paramagnetically labeled albumins, increased with increasing (DTPA-Gd3+)/BSA ratios. This effect was most pronounced at very low (DTPA-Gd3+)/BSA ratios.

New α-pyrones from Iboza riparia

Abstract The structures for umuravumbolide, 5,6-dihydro-6-(3-acetoxy-1-heptenyl)-2-pyrone, a new α-pyrone from Iboza riparia (Labiatae) and its corresponding deacylated product have been established. Deacetylboronolide was also isolated and identified by different spectroscopic techniques.

A new approach towards the synthesis of 3-amino-6-(hetero)arylpyridazines based on palladium catalyzed cross-coupling reactions

The synthesis of 3-amino-6-(hetero)arylpyridazines via palladium catalyzed cross-coupling reactions (Suzuki, Stille) on 3-amino-6-chloropyridazine (1a) and 3-amino-6-iodopyridazine (1b) has been investigated. Comparison of the results shows that there is no need to start from 1b. An improved method for the synthesis of compound 1b from 1a is also described.

Unambiguous assignments for free dimeric proanthocyanidin phenols from 2D NMR

Characterization of proanthocyanidin oligomers proceeds commonly through investigation of NMR data of their peracetates or methyl ether acetates, in conjunction with FAB-mass spectrometry and circular dichroism. Since such an approach is unsuitable in bioassay-guided isolations, we applied two-dimensional NMR techniques for the identification of dimeric proanthocyanidins. This afforded not only a powerful probe for distinction between the different procyanidin isomers, but also allowed full assignments, even for both major rotameric forms, whenever present, without the need for derivatisation. Moreover, discrimination between the crucial 6- and 8-protons and carbons was achieved after addition of traces of cadmium nitrate, resulting in the separation of the broad phenolic signals into sharp singlets. As an example of the general strategy followed in the assignment and combination of data of the different spectra available, complete analysis of underivatised procyanidin B3 or catechin-(4α→8)-catechin is discussed for the first time.