Die absolute Konfiguration der optisch aktiven β‐Hydroxy‐β‐phenyl‐propionsäuren

Schöpf, Clemens; Wüst, Willi

doi:10.1002/jlac.19596260117

Cited by 22 publications

(9 citation statements)

References 16 publications

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“…Interpretation of the 2 D spectra correlations (HSQC, HMBC, COSY) revealed compound 14 as a sinapic acid derivative, i. e., methyl 3-hydroxy-3-(4-hydroxy-3,5-dimethoxyphenyl)propanoate. Based on its negative optical rotation, the chiral centre at H-7 could be assigned as S according to the absolute stereochemical assignments given by Schöpf and Wüst [35].…”

Section: Resultsmentioning

confidence: 99%

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

et al. 2008

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The identification of targets whose interaction is likely to result in the successful treatment of a disease is of growing interest for natural product scientists. In the current study we performed an exemplary application of a virtual parallel screening approach to identify potential targets for 16 secondary metabolites isolated and identified from the aerial parts of the medicinal plant Ruta graveolens L. Low energy conformers of the isolated constituents were simultaneously screened against a set of 2208 pharmacophore models generated in-house for the in silico prediction of putative biological targets, i. e., target fishing. Based on the predicted ligand-target interactions, we focused on three biological targets, namely acetylcholinesterase (AChE), the human rhinovirus (HRV) coat protein and the cannabinoid receptor type-2 (CB 2 ). For a critical evaluation of the applied parallel screening approach, virtual hits and non-hits were assayed on the respective targets. For AChE the highest scoring virtual hit, arborinine, showed the best inhibitory in vitro activity on AChE (IC 50 34.7 μM). Determination of the anti-HRV-2 effect revealed 6,7,8-trimethoxycoumarin and arborinine to be the most active antiviral constituents with IC 50 values of 11.98 μM and 3.19 μM, respectively. Of these, arborinine was predicted virtually. Of all the molecules subjected to parallel screening, one virtual CB 2 ligand was obtained, i.e., rutamarin. Interestingly, in experimental studies only this compound showed a selective activity to the CB 2 receptor (Ki of 7.4 μM) by using a radioligand displacement assay. The applied parallel screening paradigm with constituents of R. graveolens on three different proteins has shown promise as an in silico tool for rational target fishing and pharmacological profiling of extracts and single chemical entities in natural product research.

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Section: Resultsmentioning

confidence: 99%

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

et al. 2008

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“…After 23 h, remaining alcohol 2e exhibited a high enantiomeric excess at 55% conversion, reaching 91% ee with an (S)-configuration. 13,14 In our reaction design for kinetic resolution through intermolecular acetalization, the addition of amino alcohol 2e to enol ether 3 proved beneficial. The inherent problem, however, still lies in minimizing the intermolecular acetal exchange between alcohol 2e and formed acetal 4e under acidic conditions (Figure 2a).…”

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confidence: 99%

Kinetic Resolution of Racemic Amino Alcohols through Intermolecular Acetalization Catalyzed by a Chiral Brønsted Acid

2015

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The kinetic resolution of racemic secondary alcohols is a fundamental method for obtaining enantiomerically enriched alcohols. Compared to esterification, which is a well-established method for this purpose, kinetic resolution through enantioselective intermolecular acetalization has not been reported to date despite the fact that the formation of acetals is widely adopted to protect hydroxy groups. By taking advantage of the thermodynamics of acetalization by the addition of alcohols to enol ethers, a highly efficient kinetic resolution of racemic amino alcohols was achieved for the first time and in a practical manner using a chiral phosphoric acid catalyst.

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“…They contain highly reactive double bonds, amenable to stereoselective electrophlic (1 -3) or nucleophilic attack (4, 5). Hydrogenations of the tri-or tetrasubstituted double bonds in the oxazolines thus obtained are highly stereoselective ( 4 14, 19,24,26). Furthermore, substituents may be introduced in position 4 (next to the carbamate group) by lithiation and reaction with electrophiles (products 4, 10).…”

Section: A4-13-oxazoline-3snrboxy~t~mentioning

confidence: 99%

“…-[alD = +87.5 (c = 0.95 in CHCIJ. Man riihrte 5 h bei Raumtemp., versetzte anschlieBend mit 2.13 g (10 mmol) (21), 57 (lo), 55 (19), 41 (20), 39 (11). - ( ', 3000, 2960,2935,2860, 1760, 1720, 1480, 1445, 1400, 1365, 1330, 1195, 1175 2-(tert-Butyl) -5-formyl-A'-1,3-oxazolin-3-carbonsaure-methylester (21): Zu 3.86 ml (50 mmol) D M F wurden innerhalb von 10 rnin 4.56 ml(50 mmol) POCl, getropft, und die Mischung wurde 45 min bei Raumtemp.…”

Section: 4-dicarbonsiiure-dimethylester (18c)unclassified

Substitutionen und Additionen an (R)‐2‐tert‐Butyl‐Δ⁴‐1,3‐oxazolin‐3‐carbonsäure‐methylester

Stucky

Seebàch

1989

Chem. Ber.

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Electrochemistry, oxidative decarboxylation (Hofer-Moest) Enantiomerenreine A4-1,3-Oxazoline (1 -5) mit einer tert-ButylGruppe in 2-Stellung werden uber einen elektrochemischen Schliisselschritt im 100-g-MaBstab aus Serin oder Threonin hergestellt; sie enthalten gegeniiber Elektrophilen (1 -3) oder Nucleophilen (4, 5) hochreaktive Doppelbindungen, so daB Formylierungen, Acylierungen (-+ 21, 22) oder konjugierte Additionen (-+ 11, 13) an C-5 durchgefiihrt werden k6nnen. Eine Art ortho-Metallierung (neben der Carbamoyl-Gruppe) an C-4 erlaubt es, auch in dieser Position Substituenten einzufiihren (-4, 10). SchlieBlich reagiert das Dienolat aus 5 mit Aldehyden in der exocyclischen Position (-+ 18). In so hergestellten Oxazolinen kann die tri-oder tetrasubstituierte Doppelbindung stereoselektiv hydriert werden (-+ 14, 19, 24, 26). In den meisten Fillen dirigiert die tert-ButylGruppe in 2-Stellung des Heterocyclus den Angriff von Reaktionspartnern auf die andere Seite des Fiinfringes. Eine retrosynthetische Analyse zeigt auf, welche Bindungen der urspriinglich eingesetzten Aminoduren Serin und Threonin durch die hier beschriebenen Reaktionen letztlich betroflen sind. A) Zielsetzung und Herstellung der EdukteIm Rahmen unserer Arbeiten iiber die Selbstregeneration stereogener Zentren2' stellten wir auch ungesattigte Heterocyclen vom Typ A (X, Y = NR, 0, S, SO, SOz) aus den Aminosauren Serin, Cystein und Threonin her. In diesen Heterocyclen ist das ursprungliche Chiralitatszentrum der Aminosauren nicht mehr vorhanden, sie sind aber chiral aufgrund eines Acetal-Zentrums (R' *CHXY) und enantiomerenrein aufgrund der gewahlten Synthese aus den entsprechenden Aminosauren ' ). Als besonders interessant erschienen uns die Oxazoline 1 -3 mit der sperrigen tert-Butyl-Gruppe am Acetal-Zentrum und einer Doppelbindung mit Enolether-und zugleich Methoxycarbonyl-EnaminStruktur, sowie die Ester 4 und 5, in denen die Doppelbindung des Heterocyclus zusatzlich mit einer CarbonylGruppe konjugiert ist. Wir hofften, daD die zu erwartenden vielfaltigen Reaktionen durch die tert-Butyl-Gruppe sterisch gelenkt wiirden. Durch die Verfiigbarkeit der entsprechenden Aminosauren waren auch die Enantiomeren der in Schema 1 gezeigten Oxazoline und daraus erhaltener Produkte zuganglich.Voraussetzung fur eine breit angelegte Studie war der Zugang zu diesen Heterocyclen in praparativ ergiebigem MaDstab. Der Schliisselschritt fur die Umwandlung von Serin in das an der Doppelbindung unsubstituierte Oxazolin 1 ist Enantiomerically pure A4-l,3-oxazolines (1 -5) bearing a tert-butyl group in the position 2 are prepared on a 100-g scale from serine or threonine using an electrochemical key step. They contain highly reactive double bonds, amenable to stereoselective electrophlic (1 -3) or nucleophilic attack (4, 5). Thus, Vilsmeier and Friedel-Crafts-type reactions (-21, 22) and Michael additions (-+ 11, 13) occur at C-5. Furthermore, substituents may be introduced in position 4 (next to the carbamate group) by lithiation and reaction with electrophiles (products...

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Die absolute Konfiguration der optisch aktiven β‐Hydroxy‐β‐phenyl‐propionsäuren

Cited by 22 publications

References 16 publications

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

Kinetic Resolution of Racemic Amino Alcohols through Intermolecular Acetalization Catalyzed by a Chiral Brønsted Acid

Substitutionen und Additionen an (R)‐2‐tert‐Butyl‐Δ⁴‐1,3‐oxazolin‐3‐carbonsäure‐methylester

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Die absolute Konfiguration der optisch aktiven β‐Hydroxy‐β‐phenyl‐propionsäuren

Cited by 22 publications

References 16 publications

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

In silicoTarget Fishing for Rationalized Ligand Discovery Exemplified on Constituents ofRuta graveolens

Kinetic Resolution of Racemic Amino Alcohols through Intermolecular Acetalization Catalyzed by a Chiral Brønsted Acid

Substitutionen und Additionen an (R)‐2‐tert‐Butyl‐Δ4‐1,3‐oxazolin‐3‐carbonsäure‐methylester

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Substitutionen und Additionen an (R)‐2‐tert‐Butyl‐Δ⁴‐1,3‐oxazolin‐3‐carbonsäure‐methylester