LongLarf

Synthesis
DOI: 10.1055/a-1742-2821

We have developed a two-step synthesis of dibenzotetrathiafulvalene (DBTTF) derivatives by combining the indium-catalyzed reductive dithioacetalization of oxalic acid and electron-rich aromatic dithiols with a subsequent oxidation of the resultant dithioacetals. The same transformation of electron-rich aromatic dithiols with either 9-fluorenecarboxylic acid derivatives or dicarboxylic acids effectively produced the corresponding benzo-1,3-dithiafulvene derivatives.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Synthesis
DOI: 10.1055/a-1766-2416

Preparative thin-layer chromatography (prepTLC) is a commonly used method of purification suitable for small-scale reactions. However, descriptions of the preferred methodology to load, run, and recover samples from prepTLC are non-standard and varied, making it part of the ‘hidden curriculum’ of laboratory techniques. In this article we report on the simple, cost-effective methods we use to load and collect samples from a plate, which enhance the convenience, speed, and precision of this technique.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature Chemistry, Published online: 17 March 2022; doi:10.1038/s41557-022-00898-0

Chemical biology tools have emerged as a highly significant and promising means to investigate lysine post-translational modifications (PTMs). This Review discusses different strategies using chemical biology probes to study lysine acylation and related regulatory proteins. Solutions to overcome problems in existing systems and future research directions are also proposed.

Abstract

Lysine acylation plays pivotal roles in cell physiology, including DNA transcription and repair, signal transduction, immune defense, metabolism, and many other key cellular processes. Molecular mechanisms of dysregulated lysine acylation are closely involved in the pathophysiological progress of many human diseases, most notably cancers. In recent years, chemical biology tools have become instrumental in studying the function of post-translational modifications (PTMs), identifying new “writers”, “erasers” and “readers”, and in targeted therapies. Here, we describe key developments in chemical biology approaches that have advanced the study of lysine acylation and its regulatory proteins (2016–2021). We further discuss the discovery of ligands (inhibitors and PROTACs) that are capable of targeting regulators of lysine acylation. Next, we discuss some current challenges of these chemical biology probes and suggest how chemists and biologists can utilize chemical probes with more discriminating capacity. Finally, we suggest some critical considerations in future studies of PTMs from our perspective.

Nature, Published online: 02 March 2022; doi:10.1038/s41586-021-04365-7

Abstract

A protocol for the synthesis of unsymmetrical ureas substituted by pyridyl/quinolinyl moiety has been developed. This method concluded in metal- and base-free reamination of N,N-dimethyl-N‘-hetaryl ureas with a wide range of aryl and alkyl amines. The isolated yields vary from 40 to 96% depending on the nucleophilicity of the amines. The scope of this method includes more than 50 examples. The reaction is not hindered by either donor or acceptor groups as well as diverse functionalities. The synthesis can be easily scaled to gram quantities. Theoretical calculations supported by experimental data allowed us to propose a plausible mechanism for the process. This reaction takes place through the intermediate formation of hetaryl isocyanate.

A simple prolinamide bearing a single H-bond donor urea function catalyzes the Pictet–Spengler reaction between tryptamines and α-ketoamides to afford 1,1-disubstituted tetrahydro-β-carbolines in excellent yields and enantiomeric excesses.

Abstract

The asymmetric Pictet–Spengler reaction (PSR) with aldehydes is well known. However, PSR involving ketones as electrophilic partners is far-less developed. We report herein the first examples of catalytic enantioselective PSR of tryptamines with α-ketoamides. A new class of easily accessible prolyl-urea organocatalysts bearing a single H-bond donor function catalyzes the title reaction to afford 1,1-disubstituted tetrahydro-β-carbolines in excellent yields and enantioselectivities. The kinetic isotope effect using C2-deuterium-labelled tryptamine indicates that the rearomatization of the pentahydro-β-carbolinium ion intermediate might be the rate- and the enantioselectivity-determining step.

An efficient protocol to access a set of arylated glycinamide derivatives through a C( sp ² / sp ³ )−H activation assisted by the directing group picolinamide and Pd(OAc)₂ has been developed. The methodology has a high atom economy and broad substrate scope.

Abstract

A Pd(II)-catalyzed C(sp ² /sp ³ )−H bond arylation protocol has been developed to access ortho-diaryl, ortho-mono-aryl, and biaryl-diarylmethane-glycinamide derivatives bearing picolinamide as directing group. Mechanistic details of the process have been obtained by computational modelling of the activation reaction through DFT calculations.

Nature Reviews Chemistry, Published online: 25 February 2022; doi:10.1038/s41570-022-00371-z

Nature Catalysis, Published online: 25 February 2022; doi:10.1038/s41929-022-00747-w

Isolable and hydrocarbon-soluble β-diketiminato calcium phenyls are accessible from the reaction of Ph₂Hg and [(BDI)CaH]₂. The compounds were shown to react with bromoarenes through a direct S_NAr displacement of halide, leading to the uncatalyzed formation of biaryl molecules.

Abstract

Hydrocarbon-soluble β-diketiminato phenylcalcium derivatives, which display various modes of Ca−μ₂-Ph−Ca bridging, are accessible from reactions of Ph₂Hg and [(BDI)CaH]₂. Although the resultant compounds are inert toward the C−H bonds of benzene, they yield selective and uncatalyzed biaryl formation when reacted with readily available aryl bromides.