Synthesis, Resolution, and Absolute Stereochemistry of (−)-Blestriarene C

Chiral nonracemic cis-4,5-bis(aryl) imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (−)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (−20 °C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (−)-Nutlin-3 in a 17 gram batch, and elimination of all but three chromatographic purifications.

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“…Subsequent hydrolysis of the dialkylated compound provided the desired carboxylic acid 15 in excellent yield (94%, 10.4 g). 28 …”

Section: Resultsmentioning

confidence: 99%

Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

et al. 2013

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“…[72][73][74] Das bei Raumtemperatur konfigurativ stabile 1,1'-Binaphthyl (23) (Abbildung 5) racemisiert rasch über den angeregten Triplettzustand 41 (Abbildung 10). [73] Es wurde vorgeschlagen, dass der Diradikal-Charakter des Triplettzustands die Bindungsordnung der Aryl-Aryl-Bindung erhöht, was eine Abflachung der Struktur (kleinerer Torsionswinkel a T ) zur Folge hat.…”

Section: Photochemisch Induzierte Atropisomerisierungunclassified

“…Die so gewonnene elektronische Stabilisierungsenergie senkt -trotz der stärkeren sterischen Wechselwirkungen, die aus der kürzeren Aryl-Aryl-Bindung resultieren -stark die Rotationsbarriere (E Akt.,Triplett = 8 kJ mol À1 ). Das natürliche 1,1'-Biphenanthren Bestriaren C (42) zeigt eine bemerkenswert schnelle Photoracemisierung: [74] Bestrahlen mit einer Fluoreszenzlampe führt zu einem raschen Verlust an optischer Reinheit (t 295 K = 30 min).…”

Section: Photochemisch Induzierte Atropisomerisierungunclassified

Atropselektive Synthese axial‐chiraler Biaryle

et al. 2005

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Eine rotationsgehinderte und dadurch stereogene Biarylachse ist das strukturell und stereochemisch entscheidende Element einer ständig wachsenden Zahl von Naturstoffen, chiralen Auxiliaren und Katalysatoren. Daher ist es nicht überraschend, dass im letzten Jahrzehnt bedeutende Fortschritte in der asymmetrischen Synthese axial‐chiraler Biaryle erzielt worden sind. Neben dem klassischen Zugangsweg, der direkten Aryl‐Aryl‐Kupplung, sind innovative Konzepte entwickelt worden, in denen die asymmetrische Information in ein schon vorhandenes, aber nicht optisch aktives – symmetrisches oder konfigurativ labiles – Biaryl eingeführt oder eine Aryl‐C‐Einfachbindung stereoselektiv in eine Achse umgewandelt wird. In diesem Aufsatz werden die Strategien nach den zugrunde liegenden Konzepten klassifiziert, und ihre Anwendungsbreite und ihre Beschränkungen werden anhand ausgewählter Beispiele kritisch beurteilt. Ferner werden die Voraussetzungen für das Auftreten von Axialchiralität diskutiert.

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“…12 In the current study, the fibrous roots of the pseudobulbs of B. striata were detached and their phytochemical constituents were investigated for the first time. Six biphenanthrenes, including four new 1,2′-linked (1), 1,3′-linked (2), and 1,1′-linked (3,4) biphenanthrenes, as well as two known compounds (5,6), were isolated from the 95% ethanol extract. The planar structures of 1−4 were determined by spectroscopic data interpretation.…”

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confidence: 99%

Antibacterial Biphenanthrenes from the Fibrous Roots of Bletilla striata

Qian

Jiang

et al. 2015

J. Nat. Prod.

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Four new 9',10'-dihydro-biphenanthrenes, including an unprecedented 1,2'-linked biphenanthrene, 4,7,3',5'-tetramethoxy-9',10'-dihydro(1,2'-biphenanthrene)-2,7'-diol (1), a new 1,3'-linked biphenanthrene, 4,7,7'-trimethoxy-9',10'-dihydro(1,3'-biphenanthrene)-2,2',5'-triol (2), and two new 1,1'-linked biphenanthrenes, 4,7,4'-trimethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (3) and 4,7,3',5'-tetramethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (4), as well as two known biphenanthrenes (5, 6), were isolated from a 95% ethanol extract of the fibrous roots of Bletilla striata. Their structures were determined by spectroscopic and spectrometric methods. Atropisomerism of these compounds was considered based on their chiral optical properties and potential energy surface scans at the ab initio HF/3-21G level, which revealed their racemic mixture form. Compounds 2-6 showed potent antibacterial activities against six Gram-positive bacterial strains.

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Synthesis, Resolution, and Absolute Stereochemistry of (−)-Blestriarene C

Cited by 64 publications

References 73 publications

Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

Atropselektive Synthese axial‐chiraler Biaryle

Antibacterial Biphenanthrenes from the Fibrous Roots of Bletilla striata

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