Oxazole Units Research Articles

Anti-inflammatory oxazole-, nitro- and hexahydropyrrolo[2,1-b]oxazole-containing abietane diterpenoid alkaloids from Salvia miltiorrhiza

Nine undescibed abietane diterpenoid alkaloids (DAs), salviamines G‒H (1–2), isosalviamines G‒J (3–6), and miltiorramines A‒C (7–9) were isolated from the roots of Salvia miltiorrhiza. Their chemical structures including absolute configurations were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS), combined with the calculated ECD method and single-crystal X-ray diffraction analysis. Among them, compounds 1–6 are unusual 20-nor- or 19,20-bisnor-abietane DAs with an oxazole ring. Compounds 7–8 are the first examples of DAs with a nitro group isolated from plant sources. Notably, compound 9 possesses a rare hexahydropyrrolo[2,1-b]oxazole unit that is fused in the ring B of the abietane skeleton. Bioactivity assay indicated that compound 3 showed significant anti-inflammatory activity by decreasing the gene expressions of IL-1β, IL-6, and TNF-α in LPS-induced RAW264.7 cells in a dose-dependent manner.

Tandem synthesis and antibacterial screening of new thieno[2,3-b]pyridine-fused pyrimidin-4(3H)-ones linked to thiazole or oxazole units

New two series of thieno[2,3-b]pyridine-fused pyrimidinones 1 and 2 linked to thiazole or oxazole units were prepared utilizing a three-component tandem protocol. Therefore, a mixture of 1 equiv. of 3-aminothieno[2,3-b]pyridine-2-carboxylate was first microwave irradiated with 1.5 equiv. of dimethylformamide-dimethylacetal in toluene was at 110 °C for 15 min. Next, the crude enamine was dissolved in dioxane and 1 equiv. of the respective 4-arylazole-based amines was added. The mixture was microwaved at 100 °C for 20–30 min, resulting in a 74–89% yield of the target pyrimidinones. The new products showed a wide spectrum of antibacterial activity. In general, oxazole-linked pyrimidinones 2 exceeded their analogs 1 attached to thiazole units in antibacterial activity. Hybrids 2d, and 2e, with 4-(p-tolyl)oxazole and 4-(4-methoxyphenyl)oxazole units, demonstrated the best antibacterial potency among the new products with MIC/MBC values of 4.4/8.8 and 4.2/8.5 µM, respectively. According to SwissADME, all new pyrimidinones could be classified as drug-like.

IPr*Oxa - a new class of sterically-hindered, wingtip-flexible N,C-chelating oxazole-donor N-heterocyclic carbene ligands.

N-heterocyclic carbenes (NHCs) have emerged as a major direction in ancillary ligand development for stabilization of reactive metal centers in inorganic and organometallic chemistry. In particular, wingtip-flexible NHCs have attracted significant attention due to their unique ability to provide a sterically-demanding environment for transition metals in various oxidation states. Herein, we report a new class of sterically-hindered, wingtip-flexible NHC ligands that feature N,C-chelating oxazole donors. These ligands are readily accessible through a modular arylation of oxazole derivatives. We report their synthesis and complete structural and electronic characterization. The evaluation of steric, electron-donating and π-accepting properties and coordination chemistry to Ag(I), Pd(II) and Rh(I) is described. Preliminary studies of catalytic activity in Ag, Pd and Rh-catalyzed coupling and hydrosilylation reactions are presented. This study establishes the fluxional behavior of a freely-rotatable oxazole unit, wherein the oxazolyl ring adjusts to the steric and electronic environment of the metal center. Considering the tremendous impact of sterically-hindered NHCs and their potential to stabilize reactive metals by N-chelation, we expect that this class of NHC ligands will be of broad interest in inorganic and organometallic chemistry.

A novel reversible fluorescent probe for Cu2+ and S2− ions and imaging in living cells

A novel fluorescent probe TSOC (thiazole salicylaldehyde oxazole chlorinated) was synthesized based on benzothiazole conjugated olefinic bonds with salicylicaldehyde unit as fluorophore and a phenyl oxazole unit as bonding unit. The probe could reversibly detect of Cu2+ and S2− over other common ions with longer emission and large stokes shift in an aqueous solution at pH 7.3 (DMSO-Hepes, v/v, 5:1, 10 mM). The bonding mechanism was supported through the titration experiment of fluorescence and absorption spectroscopy, 1H-NMR titration, HR-MS and DFT calculations. Moreover, the probe further exhibited good cell permeability and were successfully used to visualize Cu2+ and S2− in living cells.

Synthesis and Antiproliferative Evaluation of Novel 5-Aryl Substituted Oxazolo[4,5-b]pyridin-2-amine Derivatives

The oxazole is a well-known five-membered heterocycle containing both oxygen and nitrogen atoms in its structure. The oxazole unit is frequently found in natural products,1 including bengazole A2 a...

Substituent-Controlled Tailoring of Chalcogen-Bonded Supramolecular Nanoribbons in the Solid State.

In this work, we design and synthesize supramolecular 2,5-substituted chalcogenazolo[5,4-β]pyridine (CGP) synthons arranging in supramolecular ribbons at the solid state. A careful choice of the combination of substituents at the 2- and 5-positions on the CGP scaffold is outlined to accomplish supramolecular materials by means of multiple hybrid interactions, comprising both chalcogen and hydrogen bonds. Depending on the steric and electronic properties of the substituents, different solid-state arrangements have been achieved. Among the different moieties on the 5-position, an oxazole unit has been incorporated on the Se- and Te-congeners by Pd-catalyzed cross-coupling reaction and a supramolecular ribbon-like organization was consistently obtained at the solid state.

Crystals of Phenylene–Oxazole Oligomer with a Central Benzothiadiazole Fragment

The results of growth from solutions of organic crystals of a new π-conjugated linear oligomer (Hex-O-Ph)2-BTD consisting of benzothiadiazole (BTD), phenyl (Ph) and oxazole (O) units and n-hexyl terminal substituents are presented. Well soluble at 20°C in n-hexane (1.7 g/L) and acetone (1.9 g/L), (Hex-O-Ph)2-BTD crystals are formed in the shape of films or plates up to 8 mm long and about 10 μm thick at the liquid–air interface within five days. The polymorphism and melting parameters of the new compound are determined by the method of differential scanning calorimetry. The structure of the single-crystal film is analyzed by Х-ray diffraction. The crystal structure of (Hex-O-Ph)2-BTD is found to be formed from close-packed (001) layers with a thickness of d001 = 2.39 nm.

Synthesis and Biological Activities of Novel Pyrazole Amide Compounds Containing Substituted Oxazole Unit

Synthesis and Biological Activities of Novel Pyrazole Amide Compounds Containing Substituted Oxazole Unit

Growth of New Linear Phenylene-Oxazole Oligomers with a Central Benzothiadiazole Fragment from Solutions of Crystals

For the first time, the results on the solubility and growth of new oligomers with a single conjugated core from solutions of organic crystals are reported. The new oligomers consist of benzothiadiazole, phenylene, and oxazole units and have various terminal substituents. Using DSC and TGA methods, melting parameters are found and thermal stability upon heating is studied.

Macrocyclic Core of Salarin C: Synthesis and Oxidation.

The synthesis of the macrocyclic core of the cytotoxic natural product salarin C from the sponge Fascaplysinopsis sp. is described, with the two epoxides being replaced by alkene moieties. In the key step, ring-closing metathesis exclusively afforded the ( E)-product. NOESY-based conformational analysis of the macrolactone showed that the oxazole ring and its unsaturated side chains are located in a common plane. Mimicking the conversion of salarin C to salarin A, the trisubstituted oxazole unit embedded in the 17-membered ring underwent photooxidation on treatment with singlet oxygen, affording macrocyclic trisacylamines.

Anti-MRSA actinomycins D1-D4 from the marine sponge-associated Streptomyces sp. LHW52447

Actinomycins D1−D4 (1–4), four new D-type actinomycin analogues, were isolated from the fermentation broth of a strain of marine sponge-associated Streptomyces sp. LHW52447, together with actinomycin D (5). The structures of 1−4 were determined by a combination analysis of HRMS and NMR spectroscopic methods, and their absolute configurations of amino acids were determined by Marfey's analysis. Actinomycins D1 (1) and D2 (2) are the first two naturally occurring actinomycins with incorporation an oxazole unit into the central phenoxazinone chromophore. Both 1 and 2 showed more potent antibacterial activities against three strains of pathogenic methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 0.125–0.25 μg/mL than those of 3−5 with MIC values of 0.5–1.0 μg/mL, which suggested that the anti-MRSA activity might be enhanced by the incorporation of an additional oxazole unit. In addition, the cytotoxicity evaluation against WI-38 human diploid lung fibroblasts revealed that the incorporation of oxazole unit could decrease the cytotoxicity of actinomycins on human normal cells.

Four new cinnamoyl-phloroglucinols from the leaves of Xanthostemon chrysanthus

Four new cinnamoyl-phloroglucinols (1–4) were isolated from the leaves of Xanthostemon chrysanthus. Compounds 1 and 2 represent the first example of natural phloroglucinols with an oxazole unit. Their structures were elucidated on the basis of NMR spectroscopic data and single crystal X-ray diffraction. Compound 3 showed moderate cytotoxic activity against MDA-MB-231 and SGC-7901 cells with IC50 values of 25.26 ± 0.35 μM and 31.2 ± 0.94 μM, respectively.

Synthesis and Conformational Analysis of Quinoline–Oxazole Peptides

AbstractThe incorporation of flexible aliphatic units into otherwise rigid aromatic foldamer sequences may result in different outcomes. The flexible units may have conformational preferences of their own that can be expressed orthogonally to those of the aromatic units. Alternatively, the latter may dictate their folding behavior onto the former. Hybrid aliphatic–aromatic peptidic oligomers combining oxazole‐based (O) and quinoline‐based (Q) amino acids have been synthesized, and their folding behavior has been investigated in solution by NMR spectroscopy and CD spectroscopy, and in the solid state by X‐ray crystallography. Sequences based on the OQQ repeat motif were shown to fold into a canonical aromatic helix motif dominated by the preferences of the quinoline, whereas sequences based on OQ repetitions preferred to fold into a herringbone helix in which the conformational preference of the oxazole units is also expressed.

Molecular Design and Synthesis of a Planar Telomestatin Analogue

Hypothetical macrocycles containing eight fused oxazole units would be logical planar analogues of telomestatin, but DFT calculations suggest the presence of excessive macrocyclic ring strain in such molecules that could complicate their synthesis and/or stability. We therefore designed a planar, C4-symmetric macrocycle composed of four oxazole and four thiazole units containing little or no ring strain. Cyclo(-ox-thia)4 (1) was successfully prepared from serine and cysteine in 19 steps to furnish the first example of an octa-azole macrocycle containing eight fused azole units.

Design, Synthesis and Bioactivities Evaluation of Novel Quinazoline Analogs Containing Oxazole Units

AbstractA novel type of quinazoline derivatives, which were designed by the combination of quinazoline as the backbone and oxazole scaffold as the substituent, have been synthesized and their biological activities were evaluated for anti‐proliferative activities and EGFR inhibitory potency. Compound 12b demonstrated the most potent inhibitory activity (IC50=0.95 µmol/L for EGFR), which could be optimized as a potential EGFR inhibitor in the further study. The structures of the synthesized quinazoline analogs and all intermediates were comfirmed by 1H and 13C NMR, 2D NMR spectra, IR spectra and MS spectra.

Theoretical Design of n-Type Organic Semiconducting Materials Containing Thiazole and Oxazole Frameworks

The characteristics of molecular structure and charge transport of some new n-type organic semiconductors containing thiazole 1a-6a and oxazole 1b-6b frameworks and trifluoromethylphenyl as terminal groups were predicted using density functional theory (DFT) methods. The energy levels of HOMO and LUMO of these compounds are decreased when thiophene and furan units are replaced by thiazole and oxazole units, respectively. The same trend was observed when benzo[1,2-d:4,5-d']bisthiazole groups were replaced with benzo[1,2-d:4,5-d']bisthiazole-4,8-diones. The reorganization energies for electron of compounds are computed in a range of 0.21-0.37 eV, which is comparable to the value of 0.25 eV of well-known n-type semiconductors such as perfluoropentacene. Some important trends can be pointed out as follows: (i) replacing the core thiazolothiazole unit of compounds 1a and 2a by the larger core benzo[1,2-d:4,5-d']bisthiazole units of 3a and 4a decreases both reorganization energies for electron (λ(e)); (ii) the λ(e) values of compounds containing thiazole 2a, 4a, and 6a are smaller than those of compounds containing thiophene 1a, 3a, and 5a, respectively; (iii) there is no clear trend when replacing benzene rings of compounds 3a and 4a by quinone rings of 5a and 6a. The λ(e) values of 5 and 6 are only somewhat larger. The same trend is also found for compounds containing oxazole 1b-6b. The intermolecular charge transports in solid state of these compounds mainly occur among molecules in the same molecular layer, whereas intermolecular interactions between molecules in different molecular layers are very small. Generally, beside some experimentally reported molecules 1a-4a, the remaining molecules designed here are good candidates for n-type organic semiconducting materials with small reorganization energies for electron and low energy levels of LUMO.

Synthesis and unusual ring transformation of 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones

The reaction of 1,4-diacyl-piperazine-2,5-diones with ferrocenecarbaldehyde in the presence of tBuOK in tBuOH–DMF at room temperature afforded 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones in 69–79% yields. The attempted N(4)-acylation of these compounds with carboxylic acids (2 equiv.) in the presence of N,N′-diisopropylcarbodiimide (2 equiv.) and 4-(dimethylamino)pyridine (3 equiv.) in dichloromethane at room temperature showed that the expected 1,4-diacylated products are initially formed, but undergo further transformations leading to compounds featuring conjugated ferrocenylmethylidene, azlactone (oxazolone) and oxazole units. As shown on the basis of one example, the azlactone ring in these compounds is opened in a room-temperature reaction with hydrazine, thus yielding the corresponding acyl hydrazide. The crystal structure of the starting material and the product of this reaction were confirmed by X-ray diffraction.

N-Type Field Effect Transistors Based on Rigid Rod and Liquid Crystalline Alternating Copoly(benzobisoxazole) Imides Containing Perylene and/or Naphthalene

The synthesis, characterization, and device studies of poly(benzobisoxazole imide)s containing perylene or naphthalene units in an alternating fashion with the oxazole unit are described. Photoinduced energy transfer and charge separation were studied in methanesulfonic acid (MSA) solution via absorption, excitation, and steady-state fluorescence studies. Excitation of the bisoxazole moiety resulted in enhanced emission from the perylene bisimide unit as a result of FRET (Förster resonance energy transfer). The influence of the imide substitution into the linear chain of poly(benzobisoxazole) (PBO) on its solid-state packing was examined by wide-angle X-ray diffraction (WXRD) analysis. Bottom contact field effect transistors (FET) based on thermally annealed polymer films were fabricated and studied. The polymers showed n-type charge transport and current modulation with an on/off ratio greater than 10(2). It was observed that the FETs consisting of the random copolymer of bisoxazole containing both perylene as well as naphthalene bisimide units had higher performance parameters such as better mobility (μ(e)) and I(on)/I(off) ratio compared to those of the pristine systems.

Them-phenylene-bridged bis-oxazole 4,4′,5,5′-tetraphenyl-2,2′-m-phenylenedi-1,3-oxazole and its bulkily substituted analogue 4,4′,5,5′-tetrakis(4-tert-butylphenyl)-2,2′-m-phenylenedi-1,3-oxazole

The title m-phenylene-bridged bis-oxazoles, C(36)H(24)N(2)O(2), (I), and C(52)H(56)N(2)O(2), (II), feature different aryl substituents in the 4- and 5-positions of the oxazole units. In the solid state, aside from the different twist of the peripheral aryl rings, the molecules show distinctly different conformations, with anti and syn orientations of the O and N atoms for (I) and (II), respectively. Connected with this property, in the crystal structure of (I), extensive π-stacking is found between the molecules, while the crystal structure of (II) only involves dimer formation as the prominent packing motif.

ChemInform Abstract: Stereocontrolled Synthesis of Calyculin A: Construction of the C(26)-C( 37) Amide-Oxazole Unit.

(–)-B-[3-(Diisopropylaminodimethylsilyl)allyl]diisopinocampheylborane and Cornforth–Meyers chemistry, and Evans alkylation were employed to construct the C(26)–C(37) amide–oxazole unit of calyculin A.