Ron Hulst

Geminal Bis-ureas as Gelators for Organic Solvents : Gelation Properties and Structural Studies in Solution and in the Gel State

Several geminal bis-urea compounds were synthesised by means of an acid-catalysed condensation of various benzaldehydes with different monoalkylureas. Many of these compounds form thermoreversible gels with a number of organic solvents at very low concentrations (<3mM) and which are stable to temperatures higher than 100 degrees C. Electron microscopy revealed a three-dimensional (3D) network of intertwined fibres, which are several tens of micrometers long and have a width ranging from approximately 30 to 300 nm. The possible aggregate forms and aggregate symmetries were evaluated by means of molecular mechanics calculations. 1H NMR, 2D NMR, 13C NMR and 13C-CP/MAS NMR techniques were used to obtain information about the aggregation and possible aggregate symmetry of geminal bis-ureas in solution, in the gel state, and in the solid state.

α-Phenylethylamine based chiral phospholidines; new agents for the determination of the enantiomeric excess of chiral alcohols, amines and thiols by means of 31P NMR

The synthesis and application of two new trivalent phosphorus derivatizing agents, based upon (S)-α-phenylethylamine, for the enantiomeric excess determination of alcohols, amines and thiols using 31P NMR, is presented.

Synthesis and characteristics of biodegradable pyridinium amphiphiles used for in vitro DNA delivery

Pyridinium amphiphiles have found practical application for the delivery of DNA into eukaryotic cells. A general synthetic method starting from (iso)nicotinoyl chloride has been devised for the preparation of pyridinium amphiphiles based on (bio)degradable esters, allowing structural variation both in the hydrophobic part and in the headgroup area. By means of differential scanning calorimetry, transmission electron microscopy and UV measurements, some characteristics, including hydrolytic behaviour, have been determined. In vitro transfection ability and toxicity have been determined using the eukaryotic COS-7 cell line.

Thiol and disulfide derivatives of ephedra alkaloids 2: A mechanistic study of their effect on the addition of diethyl zinc to benzaldehyde

Thiol and disulfide derivatives of ephedrine have been shown previously to catalyse in high enantiomeric excess (ee) the reaction of diethyl zinc with benzaldehyde. We find that this reaction involves non-linear correlations between the ee of product and catalyst. Osmotic measurements indicate a high degree of aggregation of the zinc thiolates. The behaviour of the thiol derivatives deviates sharply from that of the oxygen analogue, N-methyl ephedrine.

Synthesis and Application of New Chiral Ligands for the Asymmetric Borane Reduction of Prochiral Ketones

Two chiral nonracemic γ-amino alcohols, ephedrine thiol and the corresponding (thio)-phosphoramidates and (thio)-phosphinamides have been examined as catalysts for the reduction of propiophenone by various boranes. Up to 95% e.e. can be obtained with the phosphorus derivatives.

(S)-2H-2-oxo-5,5-dimethyl-4(R)-phenyl-1,3,2-dioxaphosphorinane, a new reagent for the enantiomeric excess determination of unprotected amino acids using 31P NMR

Diastereomeric amide derivatives of title phosphorinane 2 and unprotected amino acids are easily prepared in aqueous solutions, showing well separated signals in the 31P NMR spectra allowing accurate e.e. determination.

Diastereoselective Noncovalent Synthesis of Hydrogen-Bonded Double-Rosette Assemblies

Chiral centers present either in the dimelamine components of calix[4]arene 1 or in the cyanurate components CA quantitatively induce one handedness (P or M) in the corresponding hydrogen-bonded assemblies 1(3).(CA)(6) (de>98 %). The high degree of chiral induction results from the presence of six chiral centers in close proximity (C(alpha)) to the core of the assembly. A much lower level of chiral induction is observed for assemblies with chiral centers that are more remote (C(beta)). All diastereomerically pure assemblies 1(3).(CA)(6) exhibit very high CD activities (deltavarepsilon(max) approximately 100 L mol(-1) cm(-1)), in sharp contrast to the low CD activities (deltavarepsilon(max)<or=8 L mol(-1) cm(-1)) shown by the free components. The assemblies display spontaneous resolution under thermodynamically controlled conditions (i.e., heteromeric assemblies containing both peripheral R and S centers are not observed. Remarkable assembly behavior is observed if both components 1 and CA are chiral. In general, formation of well-defined assemblies is only observed when both components contain unidirectional information for the induction of either M or P chirality.

Improved Synthesis of C2-Symmetrical Pyridinediols and Synthesis of Cs-Symmetrical Pyridinediols

Base-induced reaction of 2,6-dimethylpyridine (2,6-lutidine) (1) with two equivalents of various ketones has been reported to provide C-2-symmetrical pyridine diols 3. Closer examination reveals that competitive di-addition to a single methyl group can occur providing C-s-symmetrical pyridine diols 7. By varying the lithiation times, the formation of this side product could be maximized or minimized on the basis of a mechanistic proposal for the competing pathways. The formation of the C-s-diol 7 could be excluded completely by using potassium diisopropylamide as base; high yields of C-2-symmetrical pyridine diols 3 are obtained. Regioselective additions of 1 to (R)-fenchone and (-)-menthone were also achieved.

Catalytic Enantioselective Alkylation of Benzaldehyde with Diethylzinc Using Chiral Nonracemic (Thio)-phosphoramidates

Abstract Two chiral nonracemic γ-amino alcohols, ephedrine thiol and the corresponding (thio)-phosphoramidates have been examined as catalysts for the enantioselective alkylation of benzaldehyde by diethylzinc. Addition of titanium tetraisopropoxide increases the yield as well as the enantioselectivity; 1-phenyl-propanol is obtained in up to 98% yield and e.e. Two chiral nonracemic y-amino alcohols, ephedrine thiol and the corresponding (thio)-phosphoramidates have been examined as catalysts for the enantioselective alkylation of benzaldehyde by titanium tetraisopropoxide/diethylzinc yielding 1-phenyl-propanol in up to 98% yield and e.e.

Complexation and (templated) synthesis of rhenium complexes with cyclodextrins and cyclodextrin dimers in water

Several small, lipophilic rhenium complexes form inclusion complexes with native beta-cyclodextrin (beta-CD) and beta-CD dimers. Association constants larger than 10(9)M(-1) were obtained using dimers. The use of beta-CD also enabled the synthesis of these rhenium complexes in water, in excellent yields, through complexation of the otherwise insoluble corresponding ligands. The influence of the reaction time and temperature on the configuration of the reaction products has been investigated in depth for one of these complexes. Using a beta-CD dimer, it proved possible to specifically template the formation of one configuration. The strength of the complexes of the rhenium complexes in cyclodextrin dimers may allow radiolabeling of biomolecules.