Coupling of 1-alkyl-2-(bromomethyl)aziridines with heteroatom-centered nucleophiles towards 2-[(heteroatom)methyl]aziridines

The reactivity of 1-alkyl-2-(bromomethyl)aziridines with respect to different types of oxygen-, nitrogen- and sulphur-centered nucleophiles has been evaluated, pointing to the conclusion that these substrates can be applied successfully as synthetic equivalents for the aziridinylmethyl cation synthon towards the corresponding 2-[(heteroatom)methyl]aziridines in good yields

Microwave-assisted regioselective ring opening of non-activated aziridines by lithium aluminium hydride

A new synthetic protocol for the LiAlH4-promoted reduction of non-activated aziridines under microwave conditions was developed. Thus, ring opening of 2-(acetoxymethyl)aziridines provided the corresponding beta-amino alcohols, which were then used as eligible substrates in the synthesis of 5-methylmorpholin-2-ones via condensation with glyoxal in THF. The same procedure was applied for the preparation of novel 5(R)- and 5(S)-methylmorpholin-2-ones starting from the corresponding enantiopure 2-(hydroxymethyl)aziridines. Additionally, 2-(methoxymethyl)- and 2-(phenoxymethyl)aziridines were treated with LiAlH4 under microwave irradiation, giving rise to either isopropylamines or 1-methoxypropan-2-amines depending on the reaction conditions

Synthesis and analysis of stable isotope-labelled N-acyl homoserine lactones

Aliphatic aldehydes were deuterated at the alpha-position via a base-catalyzed exchange reaction with D2O. These deuterated building blocks were used for the synthesis of labelled analogues of quorum sensing signal molecules belonging to the three major classes of naturally occurring N-acylated homoserine lactones (AHLs), with the label on a non-enolizable and therefore stable position. Besides the application of these stable isotope-labelled AHLs as a labelled standard for analysis via isotope dilution mass spectrometry, these compounds can be used to study the metabolic fate of the fatty acid tail of the AHL-molecule. These isotope-labelled compounds were fully characterized and used to synthesize the deuterated analogues of two commonly occurring AHL-degradation products, a tetramic acid and a ring opened N-acyl homoserine

Model studies on the pattern of volatiles generated in mixtures of amino acids, lipid oxidation-derived aldehydes, and glucose

The development of flavor and browning in thermally treated foods results mainly from the Maillard reaction and lipid degradation but also from the interactions between both reaction pathways. To study these interactions, we analyzed the volatile compounds resulting from model reactions of lysine or glycine with aldehydes originating from lipid oxidation [hexanal, (E)-2-hexenal, or (2E,4E)-decadienal] in the presence and absence of glucose. The main reaction products identified in these model mixtures were carbonyl compounds, resulting essentially from amino-acid-catalyzed aldol condensation reactions. Several 2-alkylfurans were detected as well. Only a few azaheterocyclic compounds were identified, in particular 5-butyl-2-propylpyridine from (E)-2-hexenal model systems and 2-pentylpyridine from (2E,4E)-decadienal model reactions. Although few reaction products were found resulting from the condensation of an amino acid With a lipid-derived aldehyde, the amino acid plays an important role in catalyzing the degradation and further reaction of these carbonyl compounds. These results suggest that amino-acid-induced degradations and further reactions of lipid oxidation products may be of considerable importance in thermally processed foods

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

Novel N-α-haloacylated homoserine lactones, in which a halogen atom was introduced at the α-position of the carbonyl function of the N-acyl chain, have been studied as quorum sensing (QS) modulators and compared with a library of natural N-acylated homoserine lactones (AHLs). The series of novel analogues consists of α-chloro, α-bromo and α-iodo AHL analogues. Furthermore, the biological QS activity of the synthetic AHL analogues compared to the natural AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the Escherichia coli JB523 bioassay, with the α-iodo lactones being the less active ones and the α-chloro AHLs the most potent QS agonists. Most of the α-haloacylated analogues did not exhibit a significant reduction when tested in the QS inhibition test. Therefore, these novel analogues could be utilized as chemical probes for QS structure–activity studies

Rhodium-catalysed hydroformylation of N-(2-propenyl)-β-lactams as a key step in the synthesis of functionalised N-[4-(2-oxoazetidin-1-yl)but-1-enyl]acetamides

Biologically relevant functionalised N-[4-(2-oxoazetidin-1-yl)but-1-enyl]acetamides have been prepared in a two-step approach starting from N-(2-propenyl)-beta-lactams, involving initial rhodium-catalysed hydroformylation followed by subjection of the obtained aldehydes to Staudinger reaction conditions after initial imination

Intramolecular pi-pi stacking interactions in 2-substituted N,N-dibenzylaziridinium ions and their regioselectivity in nucleophilic ring-opening reactions

The ring opening of 2-substituted N,N-dibenzylaziridinium ions by bromide is known to occur exclusively at the Substituted aziridine carbon atom via ail S(N)2 mechanism, whereas the opposite regioselectivity has been observed as the main pathway for ring opening by fluoride. Similarly, the hydride-induced ring opening of 2-substituted N,N-dibenzylaziridinium ions has been shown to take place solely at the less hindered position. To gain insight into the main factors causing this difference in regioselectivity, a thorough and detailed computational analysis was performed on the hydride- and halide-induced ring openings of l-benzyl-l-(alpha-(R)-methylbenzyl)-2(S)-(phenoxymethyl)aziridinium bromide. Intramolecular pi-pi stacking interactions in the aziridinium System were investigated at a range of levels that enable a proper description of dispersive interactions; a T-stacking conformer was found to be the most stable. Ring-opening mechanisms were investigated with it variety of DFT and high level ab initio methods to test the robustness of the energetics along the pathway in terms of the electronic level of theory. The necessity to utilize explicit solvent molecules to solvate halide ions was clearly shown; the potential energy surfaces for nonsolvated and solvated cases differed dramatically. It was shown that in the presence of a kinetically viable route, product distribution will be dictated by the energetically preferred pathway; this was observed in the case of hard nucleophiles (both hydride donors and fluoride). However, For the highly polarizable soft nucleophile (bromide), it was shown that in the absence of a large energy difference between transition states leading to competing pathways, the formation of the thermodynamic product is likely to be the driving force. Distortion/interaction analysis on the transition states has shown a considerable difference in interaction energies for the solvated fluoride case, pointing to the fact that sterics plays a major role in the outcome, whereas for the bromide this difference was insignificant, suggesting bromide is less influenced by the difference in sterics

Synthesis and reactions of 1-amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones

1-Amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones, as previously unknown ring-annelated isoquinolines with a 3-aminoimidazolidin-4-one scaffold, were selectively prepared upon reacting 2-carbamoylmethyl- or 2-ethoxycarbonylmethyl-3,4-dihydroisoquinolinium salts with hydrazine hydrate. Acylation of the primary amino group with benzoyl chlorides, followed by reductive ring cleavage of the annelated 4-imidazolidinone ring and final cyclodehydration of the N,N'-diacylhydrazines resulted in the synthesis of 1-methyl-2(5-aryl-[1,3,4]oxadiazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolines which are of interest due to their potential use as bioisosteres of biologically active N-aryl-2-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl) acetamides