Photolysis of diacyl peroxides: a radical-based approach for the synthesis of functionalized amino acids

[reaction: see text] Photolysis of the amino acid derived symmetrical and unsymmetrical diacyl peroxides at 254 nm at low temperature (-78 to -196 degrees C) generates various bis(amino acids) in a concise manner and with orthogonal protection. The methodology was applied to the synthesis of (4R)-5-propyl-L-leucine (PrLeu), a component of HUN-7293.     

Continuous sample deposition from reversed-phase liquid chromatography to tracks on a matrix-assisted laser desorption/ionization precoated target for the analysis of protein digests

Peptide mass fingerprinting by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) is one of the standard high-throughput methods for protein identification today. Traditionally this method has been based on spotting peptide mixtures onto MALDI targets. While this method works well for more abundant proteins, low-abundance proteins mixed with high-abundance proteins tend to go undetected due to ion suppression effects, instrumental dynamic range limitations and chemical noise interference. We present an alternative approach where liquid chromatography (LC) effluent is continuously collected as linear tracks on a MALDI target. In this manner the chromatographic separation is spatially preserved on the target, which enables generation of off-line LC-MS and LC-MS/MS data by MALDI. LC-MALDI sample collection provides improved sensitivity and dynamic range, spatial resolution of peptides along the sample track, and permits peptide mass mapping of low-abundance proteins in mixtures containing high-abundance proteins. In this work, standard and ribosomal protein digests are resolved and captured using LC-MALDI sample collection and analyzed by MALDI-TOF-MS.     

Et3SiH + KOtBu provide multiple reactive intermediates that compete in the reactions and rearrangements of benzylnitriles and indolenines

The combination of potassium tert-butoxide and triethylsilane is unusual because it generates multiple different types of reactive intermediates simultaneously that provide access to (i) silyl radical reactions, (ii) hydrogen atom transfer reactions to closed shell molecules and to radicals, (iii) electron transfer reductions and (iv) hydride ion chemistry, giving scope for unprecedented outcomes. Until now, reactions with this reagent pair have generally been explained by reference to one of the intermediates, but we now highlight the interplay and competition between them.

The combination of potassium tert-butoxide and triethylsilane provides simultaneous access to multiple reactive intermediates, radicals, H-atom donors, hydride donors and electron donors, giving scope for unprecedented reaction outcomes.     

Infrared Observation of the Effects of Aqueous Oxidizing Agents on the Functional Groups on Carbon Surfaces

FTIR photothermal beam deflection spectroscopy (PBDS) was used to record infrared spectra of medium-temperature carbons before and after they had been subjected to treatments with aqueous HNO₃ or H₂O₂ solution. Changes in the functional groups present on the carbon surfaces can be clearly observed.     

Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron-Rich Substrates

Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and conformation. The oxidative difluorination of alkenes represents an important strategy for their preparation, yet current methods are limited in their alkene-types and tolerance of electron-rich, readily oxidized functionalities, as well as in their safety and scalability. Herein, we report a method for the difluorination of a number of unactivated alkene-types that is tolerant of electron-rich functionality, giving products that are otherwise unattainable. Key to success is the electrochemical generation of a hypervalent iodine mediator using an “ex-cell” approach, which avoids oxidative substrate decomposition. The more sustainable conditions give good to excellent yields in up to decagram scales.     

Advances in the Synthesis of Ring-Fused Benzimidazoles and Imidazobenzimidazoles

This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-f]benzimidazoles, and imidazo[5,4-f]benzimidazoles. These heterocycles have a plethora of biological activities with the iminoquinone and quinone derivatives displaying potent bioreductive antitumor activity. Synthesis is categorized according to the cyclization reaction and mechanisms are detailed. Nitrobenzene reduction, cyclization of aryl amidines, lactams and isothiocyanates are described. Protocols include condensation, cross-dehydrogenative coupling with transition metal catalysis, annulation onto benzimidazole, often using CuI-catalysis, and radical cyclization with homolytic aromatic substitution. Many oxidative transformations are under metal-free conditions, including using thermal, photochemical, and electrochemical methods. Syntheses of diazole analogues of mitomycin C derivatives are described. Traditional oxidations of o-(cycloamino)anilines using peroxides in acid via the t-amino effect remain popular.