Beilstein Journal of Organic Chemistry最新文献

Abstract

The concept of bioisostere replacement is of paramount importance in medicinal chemistry, as it can be employed as a rational to expand bioactive chemical space to tackle lead optimization issues like lack of potency, efficacy, and selectivity or pharmacokinetic/dynamic issues. One of the most important building blocks (in the sense of participating in a vast area of chemical space of biological importance) in medicinal chemistry is the 2-phenethyl moiety, a key component of diverse drug-like entities. Although the core 2-phenethylamine structure has been recognized by the drug discovery community, little attention has been given to the various ring-based rescaffolding procedures that can be conducted with this unit. In this regard, a review on the use of 2-heteroarylethylamines displaying pharmacological activity is reported. A detailed description of flexible, amine-opened motifs is provided, that describes therapeutic targets and other potent bioactive examples, which will be a valuable repository of phenyl, heteroaryl, and other replacement units of high value to the drug discovery community.

Beilstein J. Org. Chem. 2024, 20, 1880–1893. doi:10.3762/bjoc.20.163

Abstract

The Groebke–Blackburn–Bienaymé (GBB) three-component reaction, discovered in 1998, is a very efficient strategy to assemble imidazo[1,2-a]-heterocycles starting from amidines, aldehydes and isocyanides. This review aims to exhaustively describe innovative aspects of this reaction achieved during the last five years, and classifies them into five categories: synthetic methods, building blocks, scaffolds, biological activities and physical properties.

Beilstein J. Org. Chem. 2024, 20, 1839–1879. doi:10.3762/bjoc.20.162

Abstract

Functionalized 5-aryldeazaalloxazines have been successfully synthesised through a one-pot, three-component reaction involving N,N-dimethylbarbituric acid, an aromatic aldehyde and aniline. By utilizing readily available reagents, this approach opens up the opportunity for the efficient formation of a variety of 5-aryldeazaalloxazines bearing electron-donating or halogen groups. This practical method is characterised by atom economy and offers a direct route to the introduction of an aryl moiety into the C(5)-position of deazaalloxazines, thereby generating novel catalysts for photoredox catalysis without the need for subsequent purification. Thus, it significantly improves existing approaches.

Beilstein J. Org. Chem. 2024, 20, 1831–1838. doi:10.3762/bjoc.20.161

Abstract

Polycyclic aromatic systems (PASs) are pervasive compounds that have a substantial impact in chemistry and materials science. Although their specific structure–property relationships hold the key to the design of new functional molecules, a detailed understanding of these relationships remains elusive. To elucidate these relationships, we performed a data-driven investigation of the newly generated COMPAS-2 dataset, which contains ~500k molecules consisting of 11 types of aromatic and antiaromatic rings and ranging in size from one to ten rings. Our analysis explores the effects of electron count, geometry, atomic composition, and heterocyclic composition on a range of electronic molecular properties of PASs.

Beilstein J. Org. Chem. 2024, 20, 1817–1830. doi:10.3762/bjoc.20.160

Abstract

Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates without substituents on the carbon–carbon double bond have remained a formidable challenge. To address this limitation, we report herein the asymmetric bromolactonization of 5-hexenoic acid derivatives catalyzed by a BINOL-derived chiral bifunctional sulfide.

Beilstein J. Org. Chem. 2024, 20, 1794–1799. doi:10.3762/bjoc.20.158

Abstract

Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs, including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptide were confirmed by MS–MS/MS analysis for cellulosin, while clostrisin was not post-translationally modified. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and Pseudomonas aeruginosa PA14. This is the first report of lanthipeptides from the Clostridium genus produced with its native biosynthetic machinery, as well as chemically and biologically characterized. This study showcases the immense potential of genome mining in identifying new RiPP synthetases and associated bioactive peptides.

Beilstein J. Org. Chem. 2024, 20, 1800–1816. doi:10.3762/bjoc.20.159

The ability to investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V) fluorides in good isolated yields (72-90%). Stability studies revealed that bicyclic difluoro(aryl)-λ⁵-iodane 6 was much more stable in acetonitrile-d ₃ than in chloroform-d ₁, presumably due to acetonitrile coordinating to the iodine(V) centre and stabilising it via halogen bonding.

Abstract

By one-pot four- and three-component Ugi reactions involving convertible isocyanides and unexplored pyrrole-containing β-chlorovinylaldehyde, a small library of 20 bisamides with unusual behavior in post-Ugi transformations was prepared and characterized. Surprisingly, a well-documented approach to obtain peptide-containing carboxylic acids through acid hydrolysis of the convertible isocyanide moiety in the Ugi bisamides proceeded in an unexpected manner in our case, leading to the formation of derivatives of amides of heterylidenepyruvic acid. An optimized synthetic protocol for this transformation was elaborated and a plausible sequence involving the elimination of the 2-chloroacetamide moiety and the conversion of the β-chlorovinyl fragment into a vinyl one is provided.

Beilstein J. Org. Chem. 2024, 20, 1773–1784. doi:10.3762/bjoc.20.156

Abstract

Piperazines and diazepines are examples of nitrogen heterocycles present in many marketed drugs highlighting their importance in the discovery of novel bioactive compounds. However, their synthesis often faces challenges, including complex functionalization and lengthy reaction sequences. Multicomponent reactions, notably the Ugi reaction, have emerged as powerful tools to address these hurdles. Here, we have demonstrated the possibility of using the combination of arylglyoxals and carboxylic acids tethered to nonprotected deactivated amines as a powerful strategy for the synthesis of complex fused heterocycles. The limited nucleophilic character of the amino group of the anthranilic acid, indole-2-carboxylic acid, pyrrole-2-carboxylic acid or N-phenylglycine has allowed the use of these compounds in the Ugi reaction without triggering competitive reactions. The additional functional group present in the resulting Ugi adduct can be leveraged in different post-condensation strategies to easily generate multiple fused nitrogen heterocycles including benzodiazepinone and piperazinone cores.

Beilstein J. Org. Chem. 2024, 20, 1758–1766. doi:10.3762/bjoc.20.154

Abstract

We report the synthesis and characterization of naphthalene and anthracene scaffolds end-capped by cyclic imides. The solid-state structures of the N-phenyl derivatives, determined by X-ray crystallography, reveal changes in packing preference based on the number of aromatic rings in the core. The optical and electronic properties of the title compounds compare favorably with other previously described isomers and expand the toolbox of electron-deficient aromatic compounds available to organic materials chemists.

Beilstein J. Org. Chem. 2024, 20, 1767–1772. doi:10.3762/bjoc.20.155