Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids

Science, Год журнала: 2022, Номер 376(6600), С. 1481 - 1487

Опубликована: Май 26, 2022

Catalyst-controlled site-selective activation of β- and γ-methylene carbon-hydrogen (C-H) bonds free carboxylic acids is a long-standing challenge. Here we show that, with pair palladium catalysts assembled quinoline-pyridone ligands different chelate ring sizes, it possible to perform highly monolactonization reactions wide range dicarboxylic acids, generating structurally diverse synthetically useful γ- δ-lactones via or C-H activation. The remaining carboxyl group serves as versatile linchpin for further synthetic applications, demonstrated by the total synthesis two natural products, myrotheciumone A pedicellosine, from abundant acids.

Язык: Английский

---

Coumarin Analogues as Promising Anti‐Obesity Agents: In Silico Design, Synthesis, and In Vitro Pancreatic Lipase Inhibitory Activity

Chemical Biology & Drug Design, Год журнала: 2025, Номер 105(1)

Опубликована: Янв. 1, 2025

ABSTRACT A set of coumarin‐3‐carboxamide analogues were designed, synthesized, and evaluated for their ability to impede pancreatic lipase (PL) activity. Out all the analogues, 5dh 5de demonstrated promising inhibitory activity against PL, as indicated by respective IC 50 values 9.20 11.4 μM, compared Orlistat (IC = 0.97 μM). It was found that analogue inhibited PL in a competitive manner with an inhibition constant ( K i ) 4.504 μM. Additionally, docking analysis validated interactions between (MolDock score −140.251 kcal/mol) key amino acids active site, including Leu 153, Gly 76, Arg 256, His 151, Phe 77, 263. The these significantly correlated MolDock scores (Pearson's r 0.6586). Finally, molecular dynamics simulation also performed 100 ns order elucidate stability, confirmation intermolecular . results this investigation suggested complex maintained its stability despite dynamic conditions exhibiting important acids. In summary, outcomes synthesized exhibited potential inhibit

Язык: Английский

---

Construction of Oxygen‐ and Nitrogen‐based Heterocycles from p‐Quinone Methides

The Chemical Record, Год журнала: 2021, Номер 21(12), С. 4150 - 4173

Опубликована: Авг. 9, 2021

In the last few years, there has been an explosive growth in area of para-quinone methide (p-QM) chemistry. This boom is actually due to unique reactivity pattern p-QMs, and also their remarkable synthetic applications. fact, p-QMs serve as synthons for unsymmetrical diaryl- triarylmethanes, construction diverse range carbocycles heterocycles. a wide structurally complex heterocyclic frameworks could be accessed through transformations modified stable p-QMs. Therefore, main focus this review article cover recent advancements transition-metal, Lewis acid base-catalyzed/mediated p-quinone methides (p-QMs) oxygen- nitrogen-containing

Язык: Английский

---

Enzymatic Assembly of Diverse Lactone Structures: An Intramolecular C–H Functionalization Strategy

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(2), С. 1580 - 1587

Опубликована: Янв. 2, 2024

Lactones are cyclic esters with extensive applications in materials science, medicinal chemistry, and the food perfume industries. Nature's strategy for synthesis of many lactones found natural products always relies on a single type retrosynthetic strategy, C–O bond disconnection. Here, we describe set laboratory-engineered enzymes that use new-to-nature C–C bond-forming to assemble diverse lactone structures. These engineered "carbene transferases" catalyze intramolecular carbene insertions into benzylic or allylic C–H bonds, which allow different ring sizes scaffolds from simple starting materials. Starting serine-ligated cytochrome P450 variant previously other carbene-transfer activities, directed evolution generated P411-LAS-5247, exhibits high activity constructing five-membered ε-lactone, lactam, ketone (up 5600 total turnovers (TTN) >99% enantiomeric excess (ee)). Further engineering led variants P411-LAS-5249 P411-LAS-5264, deliver six-membered δ-lactones seven-membered ε-lactones, respectively, overcoming thermodynamically unfavorable strain associated these compared γ-lactones. This new was further extended complex based fused, bridged, spiro rings. The enzymatic platform developed here complements biosynthetic strategies assembly expands structural diversity accessible through functionalization.

Язык: Английский

---

Versatile Copper-Catalyzed γ-C(sp³)–H Lactonization of Aliphatic Acids

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17311 - 17317

Опубликована: Июнь 13, 2024

Site-selective C(sp3)–H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp3)–H lactonization free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant inexpensive acids; however, a versatile catalyst for this transformation with broad substrate scope remains elusive. Herein, we report simple yet broadly applicable scalable γ-lactonization reaction aliphatic enabled by copper combination Selectfluor as oxidant. This exhibits compatibility tertiary, benzylic, allylic, methylene, primary γ-C–H bonds, affording access wide range structurally diverse lactones such spiro, fused, bridged lactones. Notably, exclusive γ-methylene C–H cycloalkane acetic was observed, giving either fused or γ-lactones that are difficult other methods. δ-C–H only favored presence tertiary bonds. The synthetic utility methodology demonstrated late-stage functionalization amino acids, molecules, natural products, well two-step total (iso)mintlactones (the shortest reported date).

Язык: Английский

---

Antimicrobial Activity of Lactones

Antibiotics, Год журнала: 2022, Номер 11(10), С. 1327 - 1327

Опубликована: Сен. 29, 2022

The development of bacterial resistance to antibiotics and the consequent lack effective therapy is one biggest problems in modern medicine. A consequence these processes an urgent need continuously design develop novel antimicrobial agents. Among compounds showing potential, lactones are a group explore. For centuries, their activities have been used folk Currently, lactone described literature. Some those structures exhibit high potential some inspiration for synthesis future drugs. This paper describes recent developments on with smaller ring sizes, up seven membered ε-lactones. Their isolation from natural sources, chemical synthesis, synergistic activity antibiotics, effects quorum sensing presented herein.

Язык: Английский

---

Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 9, 2024

Abstract Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals aqueous environments. Here, we show that this challenge can be addressed through reaction engineering using immobilized peroxygenase from Agrocybe aegerita ( Aae UPO) under neat conditions, which allows for selective C-H bond oxyfunctionalization environmentally significant cyclic ethers to hemiacetals. A wide range chiral hemiacetal products prepared >99% enantiomeric excess 95170 turnover numbers UPO. Furthermore, changing medium pure organic solvent alkaline situ transformed into lactones. Lactams obtained applied albeit with low enzyme activity. These findings showcase potential UPO offer a practical approach produce mild conditions.

Язык: Английский

---

Aromas: Lovely to Smell and Nice Solvents for Polyphenols? Curcumin Solubilisation Power of Fragrances and Flavours

Molecules, Год журнала: 2024, Номер 29(2), С. 294 - 294

Опубликована: Янв. 5, 2024

Natural aromas like cinnamaldehyde are suitable solvents to extract curcuminoids, the active ingredients found in rhizomes of

Язык: Английский

---

γ-Butyrolactone Synthesis from Allylic Alcohols Using the CO₂ Radical Anion

Precision Chemistry, Год журнала: 2024, Номер 2(3), С. 88 - 95

Опубликована: Фев. 16, 2024

γ-Butyrolactone structures are commonly found in various natural products and serve as crucial building blocks organic synthesis. Consequently, the development of methods for synthesizing γ-butyrolactones has garnered significant interest within synthesis community. In this study, we present a direct highly efficient approach from allylic alcohols. Notably, study represents first instance γ-butyrolactone initiated by radical hydrocarboxylation using CO2•–, generated metal formates, followed cyclization. This two-step process is achieved through synergistic interaction photoredox hydrogen atom transfer (HAT) catalysis, resulting production with exceptional efficiency. Additionally, when employing α,α-diaryl alcohol derivatives substrates, reaction involves 1,2-aryl migration, which occurs concomitantly CO2•– addition, leading to formation 4,5-substituted lactones good yield. The artificial force induced (AFIR) method identified preferred migration pathway along potential byproduct pathways, targeted 1,2-migration was be most plausible pathway.

Язык: Английский

---

Synthetic and Semisynthetic Compounds as Antibacterials Targeting Virulence Traits in Resistant Strains: A Narrative Updated Review

Antibiotics, Год журнала: 2023, Номер 12(6), С. 963 - 963

Опубликована: Май 25, 2023

This narrative review paper provides an up-to-date overview of the potential novel synthetic and semisynthetic compounds as antibacterials that target virulence traits in resistant strains. The focused on research conducted last five years investigated a range including azoles, indoles, thiophenes, glycopeptides, pleuromutilin derivatives, lactone chalcones. emergence spread antibiotic-resistant bacterial strains is growing public health concern, new approaches are urgently needed to combat this threat. One promising approach factors, which essential for survival pathogenesis, but not growth. By targeting it may be possible reduce severity infections without promoting development resistance. We discuss mechanisms action various their antibacterials. highlights factors strategy antibiotic resistance suggests further identify optimize efficacy. findings suggest have great fight against

Язык: Английский

---