Site-selective Amide Functionalization by Catalytic Azoline Engrafting

Amide activation is a challenging transformation due to the stabilizing effect of the amide group. While enzymes can be considered as prototypical systems that have evolved to achieve high selectivity and specificity, small-molecule catalysts that functionalize the amide group may accommodate a much larger selection of substrates but currently re-main scarce. Here, by combining the desired features from both catalytic regimes we designed an artificial cyclodehy-dratase, a catalytic system for site-selective modification of peptides and natural products by engrafting heterocyclic into their scaffolds. The catalytic system features molybdenum(VI) center that was decorated with a sterically congest-ed tripod ligand. The optimized catalyst can introduce azolines into small molecules, natural products, and oligopeptides with high efficiency and minimal waste. We further demonstrate the utility of the new protocol in direct func-tionalization of a single amide group in the presence of up to seven other chemically similar positions, and direct conversion into amines and thioamides. This new mechanistic paradigm may address an unmet need for a general method for selective and sustainable functionalization of peptides and natural products.

ANTIMICROBIAL ACTIVITY STUDY OF NEW QUINAZOLIN-4(3H)-ONES AGAINST STAPHYLOCOCCUS AUREUS AND STREPTOCOCCUS PNEUMONIAE

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics

N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), regulates various gene expressions, including growth, virulence, biofilms formation, and toxin production. Considering the role of QS in bacterial pathogenicity, its modulation appears as a possible complementary approach in antibacterial strategies. Analogues and mimics of AHLs are therefore biologically relevant targets, including several families in which heterocyclic chemistry provides a strategic contribution in the molecular design and the synthetic approach. AHLs consist of three main sections, the homoserine lactone ring, the central amide group, and the side chain, which can vary in length and level of oxygenation. The purpose of this review is to summarize the contribution of heterocyclic chemistry in the design of AHLs analogues, insisting on the way heterocyclic building blocks can serve as replacements of the lactone moiety, as a bioisostere for the amide group, or as an additional pattern appended to the side chain. A few non-AHL-related heterocyclic compounds with AHL-like QS activity are also mentioned.

Enantioselective synthesis of tertiary boronic esters through catalytic asymmetric reversed hydroboration

Chiral tertiary boronic esters are important precursors to bioactive compounds and versatile synthetic intermediates to molecules containing quaternary stereocenters. The development of conjugate boryl addition to α,β-unsaturated amide has been hampered by the intrinsic low electrophilicity of the amide group. Here we show the catalytic asymmetric synthesis of enantioenriched tertiary boronic esters through hydroboration of β,β-disubstituted α,β-unsaturated amides. The Rh-catalyzed hydroboration occurs with previously unattainable selectivity to provide tertiary boronic esters in high enantioselectivity. This strategy opens a door for the hydroboration of inert Michael acceptors with high stereocontrol and may provide future applications in the synthesis of biologically active molecules.

A Convenient Synthesis and Spectral Studies of Diamines Derivatives

<div>A new series of substituted anthranilic esters derivatives linked with a 1,3-dithiolane and</div><div>benzyloximino moiety was synthesized using the simple esterfication reaction and products were</div><div>fully characterized. The isolated yields of these compounds range from 59 to 96%. 1,3-</div><div>dithiolane ester and the benzyloxy substituted diamine derivatives are white solids and stable to</div><div>air and moisture. The synthesized compounds can be exhibits UV-vis absorption properties by</div><div>their structures with a amine or amide group, It is observed that absorption maximum is excellent</div><div>for 2,6-disubstituted benzyloxy esters which can be explained by electron transfer or conjugation</div><div>is steric effect in ortho substitution from the amino group and the amide group.</div>

A Convenient Synthesis and Spectral Studies of Diamines Derivatives

<div>A new series of substituted anthranilic esters derivatives linked with a 1,3-dithiolane and</div><div>benzyloximino moiety was synthesized using the simple esterfication reaction and products were</div><div>fully characterized. The isolated yields of these compounds range from 59 to 96%. 1,3-</div><div>dithiolane ester and the benzyloxy substituted diamine derivatives are white solids and stable to</div><div>air and moisture. The synthesized compounds can be exhibits UV-vis absorption properties by</div><div>their structures with a amine or amide group, It is observed that absorption maximum is excellent</div><div>for 2,6-disubstituted benzyloxy esters which can be explained by electron transfer or conjugation</div><div>is steric effect in ortho substitution from the amino group and the amide group.</div>

Bifunctional Ligand-Assisted Cu-Catalyzed Intermolecular Cyclo-hexenone γ‑C(sp3)-H Amination: Controlled Synthesis of p-Aminophenols

A 1,10-phenanthroline-type bifunctional ligand has been developed for Cu catalyzed direct γ-C(sp3)-H amination with intermolecular anilines. Stabilizing N-centered radicals via amide group installed on the bifunctional ligands, a new catalytic system for site-selective γ-C(sp3)-H amination to synthesize p-aminophenols was established. The economical and practical approach by using oxygen as the terminal oxidant was mild and environmental friendly.

Three New Quinazoline-Containing Indole Alkaloids From the Marine-Derived Fungus Aspergillus sp. HNMF114

By feeding tryptophan to the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis, 3 new quinazoline-containing indole alkaloids, named aspertoryadins H–J (1–3), along with 16 known ones (4–19), were obtained. The structures of the new compounds were elucidated by the analysis of spectroscopic data combined with quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts and electron capture detector (ECD) spectra. Structurally, compound 3 represents the first example of this type of compound, bearing an amide group at C-3. Compounds 10 and 16 showed potent α-glucosidase inhibitory activity with IC50 values of 7.18 and 5.29 μM, and compounds 13 and 14 showed a clear activation effect on the ryanodine receptor from Spodoptera frugiperda (sfRyR), which reduced the [Ca2+]ER by 37.1 and 36.2%, respectively.

Pyrimidine-Based Push–Pull Systems with a New Anchoring Amide Group for Dye-Sensitized Solar Cells

New donor–π–acceptor pyrimidine-based dyes comprising an amide moiety as an anchoring group have been designed. The dyes were synthesized by sequential procedures based on the microwave-assisted Suzuki cross-coupling and bromination reactions. The influence of the dye structure and length of π-linker on the photophysical and electrochemical properties and on the photovoltaic effectiveness of dye-sensitized solar cells was investigated. An increase in efficiency with a decrease in the length of π-linker was revealed. The D1 dye with only one 2,5-thienylene-linker provided the highest power conversion efficiency among the fabricated dye sensitized solar cells.