Regulating Competing Supramolecular Interactions Using Ligand Concentration

Teunissen, Abraham J. P.; Paffen, Tim F. E.; Ercolani, Gianfranco; Greef, Tom F. A. de; Meijer, E. W.

doi:10.1021/jacs.6b03421

Cited by 18 publications

(20 citation statements)

References 42 publications

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“…The spectroscopic data obtained for 6a and b corresponded with literature values. 11,12) 6-(Benzyloxy)hexanal (7a) To a stirred solution of 6a (4.96 g, 23.8 mmol) in CH 2 Cl 2 (120 mL) at 0°C were added iodobenzene diacetate (11.5 g, 35.7 mmol) and TEMPO (743 mg, 4.76 mmol). After warming to 20°C and stirring for 15 h, saturated aq.…”

Section: Experimental General Methods and Materialsmentioning

confidence: 99%

Concise Synthesis of Hydroxy β-Methyl Fatty Acid Ethyl Esters

Sakai

Asakura

Morita

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Hydroxy β-methyl fatty acid ethyl esters bearing different carbon chain lengths and varying hydroxyl group positions were successfully synthesized from symmetric diols. These fatty acid derivatives are useful intermediates of chemical probes for metabolic analyses of fatty acid.Key words β-methyl fatty acid; chemical synthesis; Johnson-Claisen rearrangement; hydroxy fatty acid Fatty acids are hydrocarbon compounds that contain various lengths of saturated carbon chains, unsaturated carbon chains, and substituted carbon chains. Fatty acids and their derivatives (including phospholipids and glycerolipids) are widely distributed in living organism and have various roles as structural and metabolic substrates.1) More specifically, methyl-substituted fatty acids are widespread in both prokaryotic and eukaryotic cells. For example, phytanic acid (1) (Fig. 1), a tetramethyl-substituted fatty acid derived from phytol, is substituted at the β-position by one of the four methyl groups.2) Although fatty acids are generally metabolized by β-oxidation, the presence of a methyl group on the β-position inhibits β-oxidation, and so metabolism via α-oxidation dominates. In terms of their biological influence, the accumulation of methyl-substituted fatty acids can cause a neurotic disorder known as Refsum disease. This disease results from a deficiency in peroxisomal α-oxidation enzymes, and manifests an accumulation of 1.3) The suppression of β-oxidation by a methyl group can also be employed for molecular imaging, as probe molecules can accumulate in the target tissue. ) for myocardial imaging. Based on this importance of hydroxy β-methyl fatty acids as valuable chemical probes in metabolic analyses, we herein report the concise synthesis of hydroxy β-methyl fatty acid ethyl esters bearing different carbon chain lengths and varying hydroxyl group positions. Results and DiscussionThe synthesis of β-methylated fatty acid derivatives was carried out from the symmetric diols 1,6-hexanediol (5a) and 1,12-dodecandiol (5b) (see Chart 1). Initially, a single hydroxyl group from each diol was converted into the corresponding benzyl ether under basic conditions to give 6a and b in moderate yields, while the remaining hydroxyl group was efficiently converted to an aldehyde by a (2,2,6,6-tetramethylpiperidin-1-yl) oxyl (TEMPO)-mediated oxidation reaction. 8)The resulting aldehydes (7a, b) were then converted to allylic alcohols in good yields using propenylmagnesium bromide at −60°C, and the resulting allylic alcohols (8a, b) were heated under reflux in the presence of triethyl orthoacetate and catalytic amounts of pivalic acid to give the β-methylated γ, δ-unsaturated ethyl esters. 9) Finally, the γ, δ-unsaturated ethyl esters were reduced and the benzyl ether groups were removed under hydrogenation conditions to yield the desired ω-1-hydroxy-β-methyl fatty acids (9a, b) in good yields.Subsequently, the corresponding ω-7-hydroxy-β-methyl fatty acids were synthesized from alcohols 9a and b, as depicted in Chart 2. This was achieved throug...

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Section: Experimental General Methods and Materialsmentioning

confidence: 99%

Concise Synthesis of Hydroxy β-Methyl Fatty Acid Ethyl Esters

Sakai

Asakura

Morita

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…We hypothesized that covalently protecting the UPy moieties with a benzyl group would destabilize the intramolecular UPy–UPy dimerization21 and afford full conversion in the RCM. To verify our hypothesis, we synthesized benzyl protected ligand 12 , which afforded catenane precursor 13 after Cu(I) complexation (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

“…To circumvent the need of using a catalyst, we opted for the UV‐labile o ‐nitrobenzyl protecting group 21 , 22 in the UPys. Compound 17 was synthesized with a similar route to 14 (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

Supramolecular polymerization of a ureidopyrimidinone‐based [2]catenane prepared via ring‐closing metathesis

Teunissen

Berrocal

Corbet

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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“…Thus, model-driven engineering is defined here as the intensive utilization of computing and informatics with the aim to assess the viability of novel molecular designs and to extract design rules, thereby decreasing the time required for experimental work. The development of synthetic supramolecular systems is currently at a level of complexity that requires a similar synergistic experimental and theoretical treatment ( 4 – 6 ). Analogously, theoretical descriptions are beginning to approach the required level of predictive accuracy required for model-driven engineering ( 7 ).…”

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confidence: 99%

“…Next to the binding affinity, linker flexibility plays an important role: Rigid linkers require extremely precise ligand positioning to obtain high binding affinities and selectivity, while flexible linkers offer more freedom in molecular design at the cost of lower affinity and selectivity ( 18 – 20 ). Furthermore, additional competing equilibria can be used to enhance binding selectivity or to steer an assembly toward a preferred state ( 5 , 21 ).…”

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confidence: 99%

Model-driven engineering of supramolecular buffering by multivalency

Paffen

Teunissen

Greef

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceThe ability of chemists to regulate the concentration of molecules is extremely important. However, as reactions are slowly superseded by more complex reaction networks, new ways of regulating molecular concentrations are needed. Recently, we described a system in which the concentration of a monovalent molecule with catalytic activity was buffered over a wide concentration range by its binding to a divalent molecule. Guided by model predictions, we are able to experimentally optimize the system by increasing the valency of the buffer, with even-numbered valencies displaying superior buffering capabilities. These results allow us to understand and gain more control over the activities of molecules in complex molecular systems, thereby obtaining insights into natural systems as well as creating adaptive artificial systems.

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Regulating Competing Supramolecular Interactions Using Ligand Concentration

Cited by 18 publications

References 42 publications

Concise Synthesis of Hydroxy β-Methyl Fatty Acid Ethyl Esters

Concise Synthesis of Hydroxy β-Methyl Fatty Acid Ethyl Esters

Supramolecular polymerization of a ureidopyrimidinone‐based [2]catenane prepared via ring‐closing metathesis

Model-driven engineering of supramolecular buffering by multivalency

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