The diversity, utility and mechanistic aspects of asymmetric synthesis with ynamides developed during the last decade is discussed.

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Ubiquitin Specific Protease-13 (USP13) promotes protein de-ubiquitination and is poorly understood in neurodegeneration. USP13 is upregulated in Alzheimer’s disease (AD) and Parkinson’s disease (PD), and USP13 knockdown via shRNA reduces neurotoxic proteins and increases proteasome activity in models of neurodegeneration. We synthesized novel analogues of spautin-1 which is a non-specific USP13 inhibitor but unable to penetrate the brain. Our synthesized small molecule compounds are able to enter the brain, more potently inhibit USP13, and significantly reduce alpha-synuclein levels in vivo and in vitro. USP13 inhibition in transgenic mutant alpha-synuclein (A53T) mice increased the ubiquitination of alpha-synuclein and reduced its protein levels. The data suggest that novel USP13 inhibitors improve neurodegenerative pathology via antagonism of de-ubiquitination, thus alleviating neurotoxic protein burden in neurodegenerative diseases.

No abstract

Optical chirality sensing of unprotected amino acids, hydroxy acids, amino alcohols, amines and carboxylic acids based on a practical mix-and-measure protocol with readily available copper, iron, palladium, manganese, cerium or rhodium salts is demonstrated.

A generally useful palladium-catalyzed method for the asymmetric allylic amination with a large variety of isatins, sulfonamides, imides, amines, and N-heterocycles is introduced. A single protocol with a readily available catalyst accomplishes this reaction at room temperature with high yields and enantioselectivities often exceeding 90%, which is demonstrated with 31 examples.

A sterically encumbered aminoborane sensor is introduced and used for quantitative stereochemical analysis of monoalcohols, diols and amino alcohols. The small‐molecule probe exhibits a rigid ortho‐substituted arene scaffold with a proximate boron binding site and a triarylamine circular dichroism (CD) reporter unit which proved to be crucial for the observed chiroptical signal induction. Coordination of the chiral target molecule produces strong Cotton effects and UV changes that are readily correlated to its absolute configuration, enantiomeric composition and concentration to achieve comprehensive stereochemical analysis within a 5 % absolute error margin. The sensing method was successfully applied in the chromatography‐free analysis of less than one milligram of a crude asymmetric reaction mixture and the advantages of this chiroptical sensing approach, which is amenable to high‐throughput experimentation equipment and automation, over traditional methods is discussed.

Die Einführung breit anwendbarer chiroptischer Enantiomerenanalytik ist eine anspruchsvolle Aufgabe und erfordert in der Regel sorgfältig entwickelte molekulare Rezeptoren oder supramolekulare Verbindungen. Hier beschreiben wir die enantioselektive Sondierung von 35 Aminosäuren, Phosphonsäuren, Hydroxysäuren, Aminoalkoholen und Diaminen mit ligandenfreien Cobaltsalzen. Die chiroptische Analyse der Enantiomerenzusammensetzung und Konzentration kleinster Probemengen erfolgt mit hoher Genauigkeit mittels weit verbreiteter Cobaltsalze und Wasserstoffperoxid als Oxidationsmittel. Trotz des Fehlens eines zusätzlichen Liganden kann diese auf einfachen Cobaltsalzen basierende Analyse auf aromatische und aliphatische Verbindungen angewendet werden und ergibt intensive CD‐Signale bei hohen Wellenlängen. Diese Methode beseitigt die allgemeine Notwendigkeit von chromophoren Liganden oder der Analyt‐Liganden‐Chiralitätsinduktion, um chiroptische Signale durch Exciton‐gekoppelten Circulardichroismus zu erzeugen, und sie besticht durch operative Einfachheit, Kosteneffizienz, Abfallreduzierung und Geschwindigkeit.