Stereoselective synthesis of glycerol-based lipids

In de natuur, lipiden bestaan als een mensgel van vele verschillende maar sterk gerelateerde moleculen. Sommige lipiden hebben een unieke functie. Bijvoorbeeld sommigen specifieke triacylglycerolen uit moedermelk helpen de adsorptie van calcium in de darm van kinderen. Calcium is essentieel voor een gezonde groei. Een ander voobeeld is in visolie .Ook hier zitten specifieke tryacylglycerolen, deze zorgen voor verlagening van de slechte LDL cholesterol. Om te onderzoeken hoe deze specifieke tryacylglyercolen precise werken moeten deze worden geisoleerd uit een natuurlijke bron, dit is vaak tijdrovend werk. Een alternatief is om deze moleculen chemisch te synthetiseren. Dit vereist echter een efficiënte methodes, die zeer vaak ontbreken. Dit probleem wordt verholpen in dit proefschrift , waar nieuwe en efficiënte methoden voor het synthetiseren van verschillende ( bioactieve ) lipiden wordt gepresenteerd. Dit Onderzoek gaat niet alleen over de synthese van lipiden, maar ook hun eigenschappen worden gebestudeerd. Sommige van de lipiden zijn naar FrieslandCampina gegaan, waar ze bijdragen aaan de analyse van melkvet. Andere lipiden werden gebruikt voor onderzoek naar de werkzaamheid van antimycotica of ze leveren een bijdragen aan andere wetenschappers die metabool reactiepad studeren in Archaea

Quality assessment of food matrices on the basis of changes in content of volatile components

One of the factors influencing the quality of foodstuff matrix is content of volatile compounds -- aromatic complex.The aim of investigation is not final foodstuff matrices containing for example foreign compounds either in form of abovementioned aromatic complex, colourants, or conservation agents, but native untreated matrices particularly fruit and savouriesNative foodstuff matrices are analyzed commonly while qualitative abundance of individual components in the mixture of whole complex of volatile compounds. Every disruption of the quality of volatile complex is always alerting and points to external intervention either pointed or random.This report points out possible impacts e.g. wrapping storing or change of soil-climatic factor. However the influences of the surroundings which are indefinable in advance and can influence the quality of aromatic complex cannot be ignored

Multigram-scale chemoenzymatic synthesis of diverse aminopolycarboxylic acids as potential metallo-β-lactamase inhibitors

Toxin A, a precursor to naturally occurring aspergillomarasmine A, aspergillomarasmine B, lycomarasmine and related aminopolycarboxylic acids, was synthesized as the desired (2S,2′S)-diastereomer on a multigram-scale (&gt;99% conversion, 82% isolated yield, dr &gt; 95 : 5) from commercially available starting materials using the enzyme ethylenediamine-N,N′-disuccinic acid lyase. A single-step protection route of this chiral synthon was developed to aid N-sulfonylation/-alkylation and reductive amination at the terminal primary amine for easy derivatization, followed by global deprotection to give the corresponding toxin A derivatives, including lycomarasmine, in moderate to good yields (23-66%) and with high stereopurity (dr &gt; 95 : 5). Furthermore, a chemoenzymatic route was developed to introduce a click handle on toxin A (yield 72%, dr &gt; 95 : 5) and its cyclized congener for further analogue design. Finally, a chemoenzymatic route towards the synthesis of photocaged aspergillomarasmine B (yield 8%, dr &gt; 95 : 5) was established, prompting further steps into smart prodrug design and precision delivery. These new synthetic methodologies have the prospective of facilitating research into the finding of more selective and potent metallo-β-lactamase (MBL) inhibitors, which are urgently needed to combat MBL-based infections.</p

Multigram-scale chemoenzymatic synthesis of diverse aminopolycarboxylic acids as potential metallo-β-lactamase inhibitors

Toxin A, a precursor to naturally occurring aspergillomarasmine A, aspergillomarasmine B, lycomarasmine and related aminopolycarboxylic acids, was synthesized as the desired (2S,2′S)-diastereomer on a multigram-scale (&gt;99% conversion, 82% isolated yield, dr &gt; 95 : 5) from commercially available starting materials using the enzyme ethylenediamine-N,N′-disuccinic acid lyase. A single-step protection route of this chiral synthon was developed to aid N-sulfonylation/-alkylation and reductive amination at the terminal primary amine for easy derivatization, followed by global deprotection to give the corresponding toxin A derivatives, including lycomarasmine, in moderate to good yields (23-66%) and with high stereopurity (dr &gt; 95 : 5). Furthermore, a chemoenzymatic route was developed to introduce a click handle on toxin A (yield 72%, dr &gt; 95 : 5) and its cyclized congener for further analogue design. Finally, a chemoenzymatic route towards the synthesis of photocaged aspergillomarasmine B (yield 8%, dr &gt; 95 : 5) was established, prompting further steps into smart prodrug design and precision delivery. These new synthetic methodologies have the prospective of facilitating research into the finding of more selective and potent metallo-β-lactamase (MBL) inhibitors, which are urgently needed to combat MBL-based infections.</p

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis

In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters ("cord factor") form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn-methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material

Late-Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3') Kinases

The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug‐resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad‐spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram‐positive and Gram‐negative bacteria is phosphorylation of these amino sugars at the 3’‐position by O‐phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’‐position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi‐step synthesis, which is not appealing for pharma industry in this low‐return‐on‐investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’‐position via palladium‐catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s‐mediated resistance employing only four synthetic steps