RESUMEN
In recent years, N-heterocyclic carbenes (NHC) have gained recognition as versatile molecules capable of acting as organocatalysts in various reactions, particularly through the activation of aldehydes via Breslow-type adducts. This organocatalytic activation has enabled the production of numerous 3,4-dihydropyran-2-ones and related derivatives. In this review, we provide an overview of the production of 3,4-dihydropyran-2-ones and derivatives via organocatalytic processes involving NHCs over the past eight years. These processes involve the use of a diverse range of substrates, catalysts, and reaction conditions, which can be classified into [4+2]-and [3+3]-type cycloadditions, primarily aimed at synthesizing this skeleton due to its biological activity and multiple stereocenters. These processes are scaled up to the gram scale, and the resulting products are often directed towards epimerization and functionalization to produce more complex molecules with potential applications in the biological field. Finally, we provide a perspective and the future directions of this topic in organic synthesis.
RESUMEN
Novel Ta- MOF was synthesized under mild conditions by ultrasound irradiations. The sample was characterized by SEM, FTIR, XRD, XPS, TG and BET technique. The final structures showed high physicho-chemical properties including narrow particle size distribution, homogenous morphology, high thermal stability and remarkable surface area. Ta- MOF synthesized in this study was used as a catalyst in the synthesis of 1,4-dihydropyran derivatives. The results proved that it has a high catalyst capability. Its advantages include high recyclability, less reaction time with higher efficiency and synthesis of new1,4-dihydropyran derivatives. In the following, antimicrobial activity including antifungal and antibacterial activity of Ta- MOF nanoparticles based on Minimum Inhibitory Concentration, Minimum Fungicidal Concentration and Minimum Bactericidal Concentration were evaluated. The synthesized Ta- MOF, in addition to high catalytic properties, showed high antimicrobial activity with MIC value between 16 and -256 µg/ml, and can be introduced as an agent against bacteria and fungi.
RESUMEN
(±)-Hyperpyran A (1a/1b), a pair of new terpenoid-based bicyclic dihydropyran enantiomers, were isolated from the aerial parts of Hypericum perforatum (St. John's wort). Their structures and absolute configurations were elucidated by NMR spectroscopic analyses, ECD comparison, and X-ray crystal diffraction. Compounds 1a/1b possess hexahydrocyclopenta[c]pyran ring system and a plausible biosynthetic pathway was also proposed. In addition, compound 1a exhibited a moderate promotion of glucose uptake activity in hepatocytes.
Asunto(s)
Hypericum , Hypericum/química , Hipoglucemiantes/farmacología , Estructura Molecular , Fitoterapia , Extractos Vegetales , Aceites de Plantas , TerpenosRESUMEN
A new, modified total synthesis of (-)-cleistenolide (1) and sixteen new analogues or derivatives was achieved starting from commercially available 1,2-O-isopropylidene-α-d-glucofuranose. The synthesis of 1 proceeds in six steps and 67% overall yield, using single-carbon atom degradation of a protected chiral precursor, (Z)-selective Wittig olefination, and acid catalyzed δ-lactonization. A new Lewis acid promoted procedure for one-pot O-debenzylation/O-acylation has been developed to complete the synthesis of natural product 1 and selected analogues. The synthesized compounds were tested in vitro to evaluate their cytotoxicity against K562, HL-60, Jurkat, Raji, MCF-7, MDA-MB 231, HeLa, A549, and MRC-5 cell lines. All (-)-cleistenolide analogues exhibited significantly higher cytotoxicity than lead 1 against the majority of cell lines tested. Most of the synthesized compounds are more active than doxorubicin on at least one malignant cell line, but were almost completely inactive against normal MRC-5 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis.
Asunto(s)
Antineoplásicos/farmacología , Pironas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Pironas/síntesis química , Pironas/química , Relación Estructura-ActividadRESUMEN
The BF3·Et2O-catalysed acetolysis of steroid sapogenins diosgenin, sarsasapogenin and tigogenin in dichloromethane as the solvent instead of acetic anhydride afforded (20S)- and (20R)-22,26-epoxycholestanes (compounds 1 and 2). 22S-23-Acetylsapogenins (compounds 4) were synthesized stereospecifically from 20R-22,26-epoxycholestanes (compounds 2) in good yield. The rearrangement of 22S-23-acetylsapogenins (compounds 4) afforded novel disubstituted dihydropyran furostanol frameworks. Exhaustive NMR characterization of the obtained compounds is provided. Additionally, the structures of the critical compounds (6a and 7a) were unequivocallyconfirmed by single crystal X-ray diffraction studies.
Asunto(s)
Sapogeninas/síntesis química , Boranos , Catálisis , Óxido de Etileno , Conformación Molecular , Sapogeninas/química , EstereoisomerismoRESUMEN
Asymmetric total syntheses of dihydropyran containing natural products, (+)-eurotiumide F and (+)-eurotiumide G have been described. These total syntheses revealed the absolute configuration of eurotiumide F and G, and confirmed the reported structure of eurotiumide F and revised the reported structure of eurotiumide G. Highlight of these syntheses is thermal rearrangement with 4-methoxyisochroman-1-one derivative having propargyl ether on phenolic ether under thermal condition to construct dihydropyran ring. X-Ray crystallographic analysis of (+)-eurotiumide G clarified the stereochemistry at the C1-position.
Asunto(s)
Productos Biológicos/química , Piranos/química , Productos Biológicos/síntesis química , Cristalografía por Rayos X , Conformación Molecular , Piranos/síntesis química , Solventes/química , EstereoisomerismoRESUMEN
A versatile and economical reaction of diketene (1), aryl amines 2, cyclic 1,3-diketones 3, primary amines 4, and aryl aldehydes 5 was explored to synthesize 3,4-dihydropyran-3-carboxamide derivatives under mild conditions. Three stereogenic centers are generated in the products, and the structure of the major diastereomer of 6{1,1,3,1} was identified by X-ray diffraction and 2D NMR spectroscopy. The scope and limitation investigation provided two series of (2S,3R,4S)-chromene-3-carboxamides in good to excellent yields with high diastereoselectivity. Two products, 6{5,3,1,1} and 6{7,3,1,1}, exhibited in vitro anti-inflammatory activity with significant inhibition of pro-inflammatory cytokine IL-6 and TNF-α expression in lipopolysaccharide (LPS)-treated Raw 264.7 cells.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Interleucina-6/antagonistas & inhibidores , Piranos/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Técnicas Químicas Combinatorias , Diseño de Fármacos , Humanos , Interleucina-6/biosíntesis , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Conformación Molecular , Piranos/síntesis química , Piranos/química , Células RAW 264.7 , Estereoisomerismo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1-4) and dihydropyran (5-16) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds 2, 7, 10 and 13 confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound 4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI=3.1-7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI=1.6-1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.
Asunto(s)
Antineoplásicos/química , Cumarinas/química , Piranos/química , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Cumarinas/síntesis química , Cumarinas/toxicidad , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Conformación Molecular , Piranos/síntesis química , Piranos/toxicidad , Relación Estructura-ActividadRESUMEN
A series of bisoumarin (1-4) and dihydropyran (5-8) derivatives were successfully synthesized as new antibacterial agents. The molecular structures of three representative compounds 1, 5 and 7 were confirmed by single crystal X-ray diffraction study. Among these compounds tested toward Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC), compounds 1 and 2 displayed the most potent antibacterial activity. Additionally, the HB energy in biscoumarins 1-4 was calculated by density functional theory (DFT) [B3LYP/6-31G*] method.
Asunto(s)
Antibacterianos/clasificación , Antibacterianos/síntesis química , Cumarinas/clasificación , Cumarinas/síntesis química , Antibacterianos/farmacología , Cumarinas/farmacología , Cristalografía por Rayos X/métodos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
Two series of biscoumarin (1-3) and dihydropyran (4-12) derivatives were successfully synthesized as new antitumor and antibacterial agents. The molecular structures of four representative compounds 2, 4, 7 and 10 were confirmed by single crystal X-ray diffraction study. The synthesized compounds (1-12) were evaluated for their antitumor activities against human intestinal epithelial adenocarcinoma cell line (HuTu80), mammary adenocarcinoma cell line (4T1) and pancreatic cancer cell line (PANC1) and antibacterial activities against one drug-sensitive Staphylococcus aureus (S. aureus ATCC 29213) strain and three MRSA strains (MRSA XJ 75302, Mu50, USA 300 LAC). The further mechanism study demonstrated that the most potent compound 1 could obviously inhibit the proliferation of cancer cells via the mechanism to induce apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Cumarinas/síntesis química , Cumarinas/farmacología , Piranos/síntesis química , Piranos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Carboplatino/síntesis química , Carboplatino/química , Carboplatino/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cumarinas/química , Cristalografía por Rayos X , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Piranos/químicaRESUMEN
A novel series of biscoumarin (1-4) and dihydropyran (5-13) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT) showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB) energy in their structures.
Asunto(s)
Antibacterianos/síntesis química , Antineoplásicos/síntesis química , Cumarinas/síntesis química , Piranos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Cumarinas/química , Cumarinas/farmacología , Cristalografía por Rayos X , Humanos , Enlace de Hidrógeno , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Piranos/química , Piranos/farmacología , Staphylococcus aureus/efectos de los fármacosRESUMEN
In an attempt to find a new class antibacterial agents, a series of biscoumarins (1-4) and dihydropyrans (5-13) were successfully prepared. The molecular structures of four representative compounds, that is, 4, 5, 8 and 12 were confirmed by single crystal X-ray diffraction study. These synthesized compounds were screened for their antibacterial activity in vitro against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), USA 300 (Los Angeles County clone, LAC), Staphylococcus epidermidis (S. epidermidis ATCC 14990), methicillin-resistant S. epidermidis (MRSE XJ 75284) and Escherichia coli (E. coli ATCC 25922). Additionally, there are two classical intramolecular O-H···O hydrogen bonds (HBs) in biscoumarins 1-4 and the corresponding HB energies were further performed with the density functional theory (DFT) [B3LYP/6-31G*] method.
Asunto(s)
Antibacterianos/síntesis química , Cumarinas/farmacología , Piranos/farmacología , Antibacterianos/farmacología , Cumarinas/síntesis química , Cristalografía por Rayos X , Enlace de Hidrógeno , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Estructura Molecular , Piranos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
OBJECTIVES: Due to the increasing prevalence of drug-resistant Staphylococcus aureus infection, we develop novel 4-hydroxycoumarin derivatives as antimicrobials. METHODS: The antibacterial activity of 4-hydroxycoumarin derivatives against drug-susceptive S. aureus (ATCC 29213) and methicillin-resistant S. aureus (MRSA) were evaluated using minimal inhibitory concentration (MIC) assay; the activity of favourable compound was further observed using bacterial growth curves assay and in the MRSA infection mice. KEY FINDINGS: Compared with dihydropyran derivatives, compound 1 as one of biscoumarins showed most potent activity with MIC values of 4-8 µg/ml and apparently inhibited the growth rate of S. aureusâ ATCC 29213 and USA300 strain in concentrations of both 16 and 32 mg/ml. In the mice infected with MRSA USA300, administration of 5 mg/kg compound 1 improved the animal survival rate to 66.7%, and improved the pathological change in lung tissue compared with the infection model animals. No significant cytotoxicity of compound 1 was observed on the umbilical vein endothelial cells (HUVECs) under the concentration of 800 µg/ml. CONCLUSION: Compared with the dihydropyran derivatives, biscoumarins exhibited more promising activity against both drug-sensitive and drug-resistant S. aureus, and it is efficacious in treating MRSA infections in mouse models with a favourable safety in human cells.
Asunto(s)
4-Hidroxicumarinas/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Pulmón/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , 4-Hidroxicumarinas/biosíntesis , 4-Hidroxicumarinas/farmacología , Animales , Antibacterianos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Pulmón/microbiología , Pulmón/patología , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/patología , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Infecciones Estafilocócicas/microbiología , Staphylococcus aureusRESUMEN
Cryptocarya diacetate and each of its stereoisomers were stereoselectively synthesized in 8-16 steps. One of the three chiral carbons was converted from the chiral center of a yeast-reduction product. The other two chiral carbons were constructed by employing stereoselective allylation and syn-and anti-1,3-reductions. The enantiomeric excesses of the synthesized cryptocarya diacetate and its stereoisomers were determined to be more than 99%ee using a chiral column.
Asunto(s)
Acetatos/síntesis química , Cryptocarya/química , Piranos/química , Pironas/síntesis química , Estructura Molecular , Oxidación-Reducción , Estereoisomerismo , Levaduras/químicaRESUMEN
In the title mol-ecule, C11H10ClFO2, the benzene ring, the F atom and the O atom of the di-hydro-pyran ring are essentially coplanar, with an r.m.s. deviation of 0.007â Å. The di-hydro-pyran ring is in a half-chair conformation. In the crystal, mol-ecules are linked by pairs of weak C-Hâ¯π hydrogen bonds, forming inversion dimers.
RESUMEN
In the structure of the title compound, C12H12O3, the di-hydro-pyran ring is fused with the benzene ring. The di-hydro-pyran ring is in a half-chair conformation, with the ring O and methyl-ene C atoms positioned 1.367â (3) and 1.504â (4)â Å, respectively, on either side of the mean plane formed by the other four atoms. The meth-oxy group is coplanar with the benzene ring to which it is connected [Cb-Cb-Om-Cm torsion angle = -0.2â (4)°; b = benzene and m = meth-oxy], and similarly the aldehyde is coplanar with respect to the double bond of the di-hydro-pyran ring [Cdh-Cdh-Ca-Oa = -178.1â (3)°; dh = di-hydro-pyran and a = aldehyde]. In the crystal, mol-ecules are linked by weak meth-yl-meth-oxy C-Hâ¯O hydrogen bonds into supra-molecular chains along the a-axis direction.
RESUMEN
We herein report for the first time the successful use of the dipeptidyl peptidase IV (DPPIV/CD26) prodrug approach to guanine derivatives such as the antiviral acyclovir (ACV). The solution- and solid-phase synthesis of the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of acyclovir are reported. The synthesis of the demanding tetrapeptide amide prodrug of ACV 3 was first established in solution and successfully transferred onto solid support by using Ellman's dihydropyran (DHP) resin. In contrast with the valyl ester prodrug (valacyclovir, VACV), the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of ACV proved fully stable in PBS. Both prodrugs converted to VACV (for 4) or ACV (for 3) upon exposure to purified DPPIV/CD26 or human or bovine serum. Vildagliptin, a potent inhibitor of DPPIV/CD26 efficiently inhibited the DPPIV/CD26-catalysed hydrolysis reaction. Both amide and ester prodrugs of ACV showed pronounced anti-herpetic activity in cell culture and significantly improved the water solubility in comparison with the parent drug.