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The utilization of CO2 from flue gas as a C1 feedstock for the catalytic synthesis of high-valued oxazolidinones is highly important but challenging due to the low CO2 concentration and high activation barrier for CO2. Herein, we present an efficient and stable CuI-anchored porous covalent organic framework CuI@TpBD-COF for effective catalysis of the carboxylic cyclization reaction between propargylic amines and CO2 to produce various functionalized oxazolidinone derivatives under mild conditions. The yield is up to 99% and the turnover frequency (TOF) reaches a record value of 1058 h−1, significantly surpassing almost all previously reported metal heterogeneous catalysts. Furthermore, CuI@TpBD-COF also demonstrates efficient catalytic activity when simulated flue gas is used as the source of CO2. This work provides new guidance for the design of more efficient and eco-friendly noble-metal-free catalytic materials to drive the ideal CO2 chemical fixation process. [ABSTRACT FROM AUTHOR]

In this contribution, we describe a straightforward and efficient synthesis of oxazolidin‐2‐ones through a Cu(I)‐catalyzed four‐component coupling of amines, aldehydes, terminal alkynes, and CO2 via carboxylative cyclization of propargylamine intermediates. This strategy enables the selective synthesis of a variety of (Z)‐5‐alkylidene‐oxazolidin‐2‐ones substituted in positions 3, 4 and 5 of the heterocyclic core with a variety of functional groups, well‐tolerated in terms of scope. A mechanistic study was carried out monitoring the process in solution by different techniques (operando FTIR, multi‐nuclear NMR), with the aim of identifying the intermediates, both organic compounds and Cu(I) coordination complexes, which showed the plausible multi‐metallic nature of the catalytic intermediates (identified by X‐ray diffraction analyses on monocrystal). [ABSTRACT FROM AUTHOR]

This work involved two parts: the first part included synthesis of new Schiff bases from condensation of 2- aminobenzothiazole with different aldehydes in acidic medium, while and the second part included the synthesis of Oxazolidinones from reaction of the prepared Schiff bases with glycine to produce new heterocyclic. Compounds. The structure of prepared compounds were characterized by 1H-NMR, FT-IR techniques and their biological activity was assessed. [ABSTRACT FROM AUTHOR]

A facile multicomponent, catalyst‐free oxazolidinone synthesis from primary aliphatic or aromatic amines, dibromoethane (DBE), and the usage of either cesium carbonate or cesium hydrogencarbonate as the simultaneous base and C1 source is reported. The applicability of this technically simple reaction was demonstrated by a broad scope with generally high yields, enabling concise late‐stage functionalization of amino groups into N‐substituted oxazolidinones. The proposed operating reaction mechanism consists of a first‐step nucleophilic substitution reaction between DBE and the primary amine, followed by the formation of a carbamate or carbonate intermediate and subsequent cyclization. Additional versatility of the herein‐developed protocol has been showcased in a medicinal chemistry approach by the generation of an oxazolidinone‐modified dipeptidyl peptidase 8 (DPP8) inhibitor. [ABSTRACT FROM AUTHOR]

Cycloaddition of carbon dioxide (CO2) with aziridine catalyzed by a zinc‐salen having B−N coordinated phenanthroimidazole motif as a photocatalyst (1), at 1 bar CO2 pressure and room temperature under solvent free condition is presented. The photocatalyst exhibited excellent selectivity and tolerates a variety of substituted aziridines, and successfully produces the corresponding oxazolidinones at mild conditions. [ABSTRACT FROM AUTHOR]

The protonation of commercially available porphyrin ligands yields a class of bifunctional catalysts able to promote the synthesis of N‐alkyl oxazolidinones by CO2 cycloaddition to corresponding aziridines. The catalytic system does not require the presence of any Lewis base or additive, and shows interesting features both in terms of cost effectiveness and eco‐compatibility. The metal‐free methodology is active even with a low catalytic loading of 1 % mol, and the chemical stability of the protonated porphyrin allowed it to be recycled three times without any decrease in performance. In addition, a DFT study was performed in order to suggest how a simple protonated porphyrin can mediate CO2 cycloaddition to aziridines to yield oxazolidinones. [ABSTRACT FROM AUTHOR]

A polystyrene-supported 1,5,7-triazabicyclodec-5-ene (TBD) was used as a highly recyclable and stable catalyst for the conversion of epoxy amines into various 2-oxazolidone scaffolds. This approach combines the use of CO2 as an attractive, cheap and abundant C1 source with a halide-free, organocatalytic continuous flow approach to promote the efficient synthesis of a small library of pharmaceutically relevant 2-substituted oxazolidinones, including the known drug Toloxatone. A packed bed reactor containing the same batch of immobilized catalyst could be applied for the continuous synthesis of a series of heterocyclic products over a two week period without significant changes in catalytic activity. [ABSTRACT FROM AUTHOR]

The given article describes the synthesis of 2-Oxazolidinone ring via proline catalyzed stereoselective α-aminoxylation of aldehyde. 2-Oxazolidinone ring is a common core structure during the synthesis of oxazolidinones class molecules. Using this simple, facile and efficient methodology, Linezolid and sutezolid were prepared using asymmetric catalysis. Selective α-aminoxylation was achieved on corresponding aldehyde with great enantiomeric excess to get intermediate (5) using catalytic amount of low cost proline. The oxazolidinone ring was then constructed on common intermediate (5) which was then further converted to Oxazolidinone class compounds like Sutezolid and Eperezolid. [ABSTRACT FROM AUTHOR]

The reaction conditions for an enantiospecific synthesis of various N-aryl-oxazolidinones from N-arylcarbamates and (R) or (S) epichlorohydrin were optimized. The N-aryl-oxazolidinones were applied to the synthesis of compounds of biological interest such as DuP 721, toloxatone and a linezolid analogue. [ABSTRACT FROM AUTHOR]

Herein, we have developed a rhodium-catalyzed C–H functionalization and subsequent intramolecular ring-opening/cyclization of vinylene carbonate with 2-pyrrolyl/indolylanilines, which leads to oxazolidinones in moderate to good yields. In this transformation, vinylene carbonate only eliminates one oxygen atom rather than –CO3 or CO2. Furthermore, some control experiments are conducted to elucidate the reaction mechanism. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed aerobic oxidative azo‐ene cyclization has been developed. The developed CuI/DMAP/O2 system efficiently facilitates the aerobic oxidation of ene‐containing hydrazides to azo compounds, which undergo azo‐ene cyclizations for the synthesis of oxazolidinones. In addition, the present approach enables the synthesis of lactams, as well as a nitroso‐ene cyclization. Preliminary mechanistic studies revealed that two carbonyl groups were essential for the successful azo‐ene cyclization and that a concerted mechanism might be plausible for this azo‐ene cyclization. [ABSTRACT FROM AUTHOR]

Chiral oxazolidinones are of significance in both medicinal and synthetic chemistry, while preparing these compounds usually involves using expensive starting materials and harsh reaction conditions. Herein, a one‐pot biocatalytic cascade process was developed for stereo‐ and regioselective aminohydroxylation of diverse alkenes by combining styrene monooxygenase and halohydrin dehalogenase, providing an approach to enantiopure oxazolidinones. [ABSTRACT FROM AUTHOR]

CO2‐transformations into high value‐added products have become a fascinating area in green chemistry. Herein, a Ru(III)‐porphyrin catalyst (RuCl3 ⋅ 3H2O−H2TPP) was found highly efficient in the three‐component reaction of CO2, aliphatic amines and dichloroethane (or its derivative) for synthesis of oxazolidinones in the yields of 71∼91%. It was indicated by means of the control experiments and UV‐vis spectra that CO2 was stoichiometrically activated by the involved aliphatic amine substrates to form a stable carbamate salt while 1,2‐dichloroethane (or its derivative) was independently activated by the involved Ru(III)‐porphyrin catalyst. The combination of CO2‐activation by aliphatic amines with 1,2‐dichloroethane activation by Ru(III)‐porphyrin catalyst cooperatively contributed to this successful transformation. [ABSTRACT FROM AUTHOR]

Stabilized by a bulky N‐heterocyclic carbene [BPDPr, 1,3‐bis(2,6‐diisopropylphenyl)‐1,3‐diazonine‐2‐ylidene] ligand, new silver carboxylate complexes of the form BPDPrAgO2C‐R (R=Me, Ph) have been synthesized and fully characterized in solution and in the solid state and implemented as sole catalysts (base‐, additive‐, and, in some cases, solvent‐free) in the challenging fixation of carbon dioxide to unsubstituted propargylic derivatives for the synthesis of oxazolidinones and α‐methylene cyclic carbonates. Derived from X‐ray diffraction studies, the molecular geometry and the concept of buried volume were employed to describe the structural and steric features of these silver complexes. Their stability and efficiency as catalysts have been demonstrated by the synthesis of 29 carboxylation products (72–98 % yield) at low catalyst loadings (0.01–1.5 mol%). Characteristics are high turnover numbers (up to 9400), catalyst recyclability (up to 96 % yield after the 7th cycle with no decomposition of the silver complex), and the possibility to scale‐up the reaction. [ABSTRACT FROM AUTHOR]

The preparation of oxazolidinones by the hypervalent iodine mediated cyclization of allylcarbamates is described. A versatile range of substrates can be converted into substituted oxazolidinones primed for further transformations. Derivatization of the products at both ends is demonstrated. A preliminary attempt at the enantioselective formation of an oxazolidinone using a chiral iodane is also presented. [ABSTRACT FROM AUTHOR]

• Heteroleptic Fe-bisiminopyridine catalysts for cyclic carbonate synthesis. • Ligand functionalization as epoxide activator; hydrogen bond donor of hydroxyl group. • Ligand functionalization as CO 2 activator; nucleophilic imidazole group. • Sustainable and efficient Fe catalytic system with 0.05 mol % of catalyst loading. Novel, efficient and multifunctional binary systems consisting of Fe-bisiminopyridine complexes and additives are presented as effective catalysts for the synthesis of cyclic carbonates from epoxides and carbon dioxide. Due to the synergistic effects arising from the presence of a hydrogen bond donor and a carbon dioxide activator in well-designed heteroleptic ligands, the catalysts exhibited excellent capabilities and selectivities in carbon dioxide utilization at 50 °C and 5 bar pressure under solvent-free conditions. The control experiments and DFT calculations proposed the cooperative mechanism with functional groups combined. The reaction scope was successfully expanded to the synthesis of oxazolidinones with N -alkyl substituted aziridines. [ABSTRACT FROM AUTHOR]

Oxazolidinone synthesis through the coupling of carbon dioxide and aziridines was catalysed by an aluminium(salphen) complex at 50–100 °C and 1–10 bar pressure under solvent‐free conditions. The process was applicable to a variety of substituted aziridines, giving products with high regioselectivity. It involved the use of a sustainable and reusable aluminium‐based catalyst, used carbon dioxide as a C1 source and provided access to pharmaceutically important oxazolidinones as illustrated by a total synthesis of toloxatone. This protocol was scalable, and the catalyst could be recovered and reused. A catalytic cycle was proposed based on stereochemical, kinetic and Hammett studies. [ABSTRACT FROM AUTHOR]

Abstract Carbon-heteoratom chemistry is a method of choice for rapid construction of complex molecules. In the recent decade, its various applications flourished thanks to the click chemistry approach. Herein, we use a combination of C-X bond formation reactions to complete the synthesis of 1,2,3-triazolyl spirooxazolidines, bearing the fluorenylmethoxycarbonyl (fmoc) substituent. Thanks to the application of 2D-NMR spectroscopic methods and a multilevel computational approach, including a medicinal chemistry – inspired conformational search, PM7 semiempirical and DFT-based geometry optimization finalized with DFT-GIAO NMR shielding constant calculation, we were able to investigate the conformational space and assign cis/trans configuration in complex NMR spectra. For the obtained fmoc derivatives we recorded UV-VIS absorption and emission spectra. The obtained compounds contain pharmacophoric groups characteristic for endocannabinoid system modulators- CB1 receptor ligands or FAAH inhibitors. Graphical abstract Image 1 Highlights • An efficient synthetic pathway towards novel spirooxazolidine derivatives. • PM7 semiempirical studies explored large conformational space. • 1D and 2D NMR combined with DFT allowed to explain complex spectra. • UV-VIS absorption and emission spectra were recorded. • NOESY spectra indicated dimer formation. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The protic ionic liquid [HDBU][Im] was easily prepared from easily accessible materials. • [HDBU][Im] was developed as an efficient catalyst for carboxylative cyclization of the anilines with cyclic carbonate. • This protocol offers low catalyst loading, wide functionality tolerance and recycling of the catalyst. • This method can be regarded as indirect path to CO 2 fixation. • Bifunctional role of [HDBU][Im] is verified by NMR technique and DFT study. Abstract The thermodynamic stability and kinetic inertness represent substantial obstacles for direct chemical transformation of CO 2. Consequently, conversion of the CO 2 equivalent in an efficient and energy-saving manner has gained much attention being viewed as an indirect pathway to chemical utilization of CO 2. In this article, we would like to report the synthesis of oxazolidinones via the carboxylative cyclization of anilines with cyclic carbonate using protic ionic liquid 1,8-diazabicyclo[5.4.0]-7-undecenium imidazolide [HDBU][Im] as the bifunctional catalyst under mild conditions without addition of conventional organic solvents. The distinguished features of this protocol include low catalyst loading, wide functionality tolerance and convenient recycling of the catalyst. A series of functional groups such as Cl, Br, CH 3 , OCH 3 and NO 2 can be well tolerated under the reaction conditions, providing the corresponding products in moderate to good yields (61–92%). In addition, to shed light on the cooperative interactions of [HDBU][Im]/EC and [HDBU][Im]/aniline, NMR technique and DFT study were also performed, respectively. [ABSTRACT FROM AUTHOR]

The formal synthesis of (–)‐PHTX is described. Our approach was based on the anodic cyanation of (S)‐1‐(1‐phenylethyl)‐piperidine (–)‐1 to afford α‐aminonitrile 2 in 85 % yield in a 53:47 dr. The presence of the α‐phenylethyl group as the chiral auxiliary ensured the control of the absolute configuration of the future C6 spiro‐center during the alkylation step of 2, which was carried out with 1‐bromo‐4‐chlorobutane. Next, elaboration of the 1‐azaspiro[5,5]undecane‐7‐one ring system was achieved in a two‐step sequence, involving (a) a Thorpe‐Ziegler annulation, and (b) the hydrolysis–decarboxylation of enaminonitrile (–)‐5 to afford spiroketone (+)‐6 in >99:1 dr. Finally, the incorporation of the future C7 butyl chain was carried out stereoselectively through a new reaction sequence which involved the synthesis of tricyclic oxazolidinone (–)‐11 and alkylation of the intermediary syn‐fluorohydrin (+)‐13 with nBuMgCl to form oxazolidinone (+)‐15 in an overall 19 % yield from (–)‐1. The stereoselective synthesis of spiropiperidone (+)‐9, a known intermediate to PHTX, has been achieved in an overall 66 % yield from 2. The introduction of the future C7 butyl chain of the title alkaloid has been achieved by condensing the fluorohydrin (+)‐13 with the corresponding Grignard reagent. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety. • Compound 10e exhibited a MIC value of 0.125 μg/mL against all tested bacteria. • The potency of compound 10e against LREF was 64-fold higher than that of linezolid. • Compound 10e was non-cytotoxic with an IC 50 value of 91.04 μM against HepG2 cell. Abstract Novel biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety were designed, synthesized and evaluated for their antibacterial activity. The key compounds 7 and 9 were synthesized by the knoevenagel condensation of intermediate aldehyde 5 with rhodanine derivatives 6a−6b. The preliminary study showed that compounds 7 , 9 and 10e exhibited potent antibacterial activity with MIC values of 0.125 µg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as the positive controls. The most promising compound 10e exhibited potent antibacterial activity against tested clinical isolates of MRSA, MSSA, VRE and LREF with MIC values in the range of 0.125–0.5 µg/mL, and the potency of 10e against clinical isolates of LREF was 64-fold higher than that of linezolid. Moreover, compound 10e was non-cytotoxic with an IC 50 value of 91.04 μM against HepG2 cell. Together, compound 10e might serve as a novel antibacterial agent for further investigation. [ABSTRACT FROM AUTHOR]

Abstract A series of linezolid analogues containing a hydrazone moiety were designed, synthesized and evaluated for their antibacterial activity. Most compounds exhibited more potent antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE pathogens as compared with linezolid and radezolid. Compounds 9a , 9c , 9f , 9g , 10m and 10t were more potent against tested clinical isolates of MRSA, MSSA, VRE and LREF as compared to linezolid. Compound 9a exhibited comparable activity with linezolid against human MAO-A for safety evaluation and showed moderate metabolism in human liver microsome. The most promising compound 9a showed remarkable antibacterial activity against S.aureus , MRSA, MSSA, LREF and VRE pathogens with MIC value of 0.0675 mg/mL, respectively, which was 15- to 30-fold more potent than linezolid. Graphical abstract Image 1 Highlights • Biaryloxazolidinone analogues containing a hydrazone moiety. • Compound 9a exhibited a MIC value of 0.0675 μg/mL against all tested bacteria. • The potency of 9a against LREF was 15–30-fold higher than that of linezolid. • 9a exhibited comparable inhibitory activity with linezolid against human MAO-A. [ABSTRACT FROM AUTHOR]

Overuse of fossil energy has accelerated the development of industrialization and improved the quality of human life. However, it also leads to the excessive emission of CO 2 , and the greenhouse effect is threatening global climate stability and human health. Various countries have implemented measures and initiatives to promote carbon emission reduction and the carbon cycle. Chemical capture and utilizing CO 2 generated by fossil energy combustion has proved an efficient and valuable method. This review describes the recent progress in synthesizing high-value-added oxazolidinones from CO 2 as a C1 source. Firstly, the development and value of oxazolidinones are discussed, and the necessity of finding efficient and green chemical synthesis methods for oxazolidinones is proved. Furthermore, the significance of the CO 2 cycloaddition reaction in the green and efficient synthesis of oxazolidinones is introduced, and we summarize and compare various transition metal-based and organic-based reaction systems that catalyze the cycloaddition reaction of CO 2 to oxazolidinones. In order to achieve potential industrial applications, the significance of novel heterogeneous catalysts, such as atomically dispersed catalysis for the CO 2 reduction reaction, is expounded by comparing the characteristics of homogeneous and heterogeneous catalysis. Finally, the interaction mechanism of cycloaddition reaction between CO 2 and N-propargylamine is discussed in the metallic and metal-free catalytic system, which provides insights for the precise design and control of the reaction and promotes the further development of catalytic systems. [Display omitted] • Currently, various methods have been developed for the synthesis of oxazolidinones, among which the CO 2 cycloaddition reaction shows the most challenge and potential in organic chemistry. • Therefore, the fabrication of well-defined catalysts and precise control of the reaction process are of great significance. • In this context, we focused on the significance of oxazolidinones synthesis and the influence of different catalytic systems on CO 2 cycloaddition reactions. • We analyzed and summarized the interaction mechanism of these reactions hoping to stimulate the enthusiasm and thinking of researchers in this field. [ABSTRACT FROM AUTHOR]

Annulation, carbonate C1 source, DPP8 and DPP9 inhibitors, multicomponent reactions, oxazolidinones Front Cover: Facile Multicomponent Synthesis of Oxazolidinones from Primary Amines and Cesium (Hydrogen)Carbonate (Eur. J. Org. Keywords: annulation; carbonate C1 source; DPP8 and DPP9 inhibitors; multicomponent reactions; oxazolidinones EN annulation carbonate C1 source DPP8 and DPP9 inhibitors multicomponent reactions oxazolidinones 1 1 1 07/19/23 20230717 NES 230717 B The Front Cover b illustrates the straightforward synthesis pathway leading to oxazolidinones like a highway without any curves or obstacles. [Extracted from the article]

New class of chiral ionic liquids/ionic salts based on 2-oxazolidinone were designed and synthesized using a very simple method and in good yields. The properties of these compounds were studied. [ABSTRACT FROM AUTHOR]

A stereoselective and simple method for the synthesis of trans-2-hydroxymethyl-N-alkyl-1,3-oxazolidin-2-ones is described. The synthesis involved the reduction of trans-aziridine-2-carboxylates with LiAlH4, followed by a ring opening and a cyclization reaction in the presence of methyl chloroformate to afford the target trans-oxazolidinones in completely regio- and stereoselective process. A plausible reaction mechanism has been proposed involving an SN1 pathway and a detailed computational study of this mechanistic process has been carried out using theoretical calculations. [ABSTRACT FROM AUTHOR]

Abstract: An effective three‐component fixation of atmospheric CO2 with readily available 1,2‐dichloroethane and aromatic amine toward oxazolidinones catalyzed by in situ NHC was developed. The reaction occurred in good to excellent yields with good generality and wide functional group tolerance, including challenging steric hindered substituted‐dichloroethane (e.g. 1,2‐dichloropropane and 2,3‐dichlorobutane). The catalytic system is not sensitive to air and moisture, and high yield of oxazolidinone was achieved even with about 0.3 atm of pressure of carbon dioxide. The mechanistic study suggests that the reaction catalyze by in situ NHC via NHC‐CO2 adduct, 1‐butyl‐3‐methylimidazolium‐2‐carboxylate as intermediate and aminochloride involves in reaction pathways. The catalyst can be recycled for at least 3 times without obvious loss of catalytic activity. The protocol is also effective to prepare six‐membered 3‐aryl‐1,3‐oxazinan‐2‐one and even seven‐membered 3‐aryl‐1,3‐oxazepan‐2‐one, when 1,3‐dichloropropane and 1,4‐dichlorobutane was employed. [ABSTRACT FROM AUTHOR]

RBx 11760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11760 in PLA–PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11760 loaded NPs were found to be 106.4 nm and −22.2 mV, respectively. The absolute size of nanoparticles by HRTEM was found to be approximately 80 nm. In vitro antibacterial agar well diffusion assay showed clear zone of inhibition of bacterial growth. In pharmacokinetic study, nanoparticle showed 4.6-fold and 7-fold increase in AUC inf and half-life, respectively, as compared to free drug. RBx 11760 nanoparticle significantly reduced bacterial counts in lungs and improved the survival rate of immunocompromised mice as compared to free drugs. Thus, RBx 11760 loaded nanoparticles have strong potential to be used as nanomedicine against sensitive and drug resistant Staphylococcus aureus infections. [ABSTRACT FROM AUTHOR]

A new porous metal–metalloporphyrin framework, MMPF-10, has been constructed from an octatopic porphyrin ligand, which links copper paddlewheel units to form a framework with fmj topology. In situ metallation of the porphyrin ligands provides MMPF-10 with two unique accessible Cu(ii) centers. This allows it to behave as an efficient Lewis acid catalyst in the first reported reaction of CO2 with aziridines to synthesize oxazolidinones catalyzed by an MMPF. [ABSTRACT FROM AUTHOR]

This study investigates the potential application of the (Ammonio)butane-1-sulfonate modified Spirulina (Arthrospira) platensis biomasses in the synthesis of 3-aryl-2-oxazolidinones from CO, ethylene oxide, and anilines. High catalytic activity and ease of recovery from the reaction mixture using filtration and several reuse times without significant losses in performance are additional eco-friendly attributes of this catalytic system. The effects of the structure of ionic liquid on the catalytic performance were investigated and the various reaction conditions were optimized. This observation was exploited in the direct and selective chemical fixation of CO, affording high degrees of CO capture and conversion. Graphical Abstract: [ABSTRACT FROM AUTHOR]

A straightforward method to construct oxazolidinones through a three-component reaction involving CO2, epoxides, and amines promoted by a combination of Bu4NI and 1,8-diazabicyclo[5.4.0]undec-7-ene was developed. A wide range of aromatic and aliphatic amines and monosubstituted epoxides were converted into 3,5-disubstituted-2-oxazolidines in up to 95 % yield. This metal-free and easily available catalytic system was applicable to a broad range of substrates, including conventionally challenging ones such as aliphatic epoxides, at atmospheric pressure. Preliminary mechanistic studies suggested a reaction pathway involving β-amino alcohols. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. Evidence suggests that the specific mutations in IDH1 are critical to the growth and reproduction of some tumor cells such as gliomas and acute myeloid leukemia, emerging as an attractive antitumor target. In order to discovery potent new mutant IDH1 inhibitors, we designed, synthesized and evaluated a series of allosteric mIDH1 inhibitors harboring the scaffold of 3-pyrazine-2-yl-oxazolidin-2-ones. All tested compounds effectively suppress the D-2-hydroxyglutarate (D-2-HG) production in cells transfected with IDH1-R132H and IDH1-R132C mutations at 10 μM and 50 μM. Importantly, compound 3g owns the similar inhibitory activity to the positive agent NI-1 and shows no significant toxicity at the two concentrations. The parallel artificial membrane permeation assay of the blood–brain barrier (PAMPA-BBB) identified 3g with a good ability to penetrate the blood–brain barrier (BBB). These findings indicate that 3g deserves further optimization as a lead compound for the treatment of patients with IDH1 mutated brain cancers. [ABSTRACT FROM AUTHOR]

The reactions of acid hydrolysis of 5-(α-halobenzyl)- and 5-benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones were studied. A possibility of the synthesis of corresponding α-hydroxy acids was shown. [ABSTRACT FROM AUTHOR]

Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (<400), ii) high polarity (clogD 7.4 <1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts. [ABSTRACT FROM AUTHOR]

Preparation of a range of oxazolidinones, including enantioenriched N-aryl-substituted oxazolidinones, in which tetraarylphosphonium salts (TAPS) catalyze the [3 + 2] coupling reaction of isocyanates and epoxides effectively, is described. The key finding is a Brønsted acid/halide ion bifunctional catalyst that can accelerate epoxide ring opening with high regioselectivity. Mechanistic studies disclosed that the ylide generated from TAPS, along with the formation of halohydrins, plays a crucial role in the reaction with isocyanates. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a Gram-negative pathogenic bacterium responsible for severe infections, and it is naturally resistant to many clinically approved antibiotic families. Oxazolidinone antibiotics are active against many Gram-positive bacteria, but are inactive against P. aeruginosa . Increasing the uptake of oxazolidinones through the bacterial envelope could lead to an increased antibiotic effect. Pyochelin is a siderophore of P. aeruginosa which delivers external iron to the bacterial cytoplasm and is a potential vector for the development of Trojan Horse oxazolidinone conjugates. Novel pyochelin-oxazolidinone conjugates were synthesized using an unexpectedly regioselective peptide coupling between an amine functionalized pyochelin and oxazolidinones functionalized with a terminal carboxylate. [ABSTRACT FROM AUTHOR]

Improvement of subtype selectivity of an inhibitor’s binding activity using the conformational restriction approach has become an effective strategy in drug discovery. In this study, we applied this approach to PDE4 inhibitors and designed a series of novel oxazolidinone-fused 1,2,3,4-tetrahydroisoquinoline derivatives as conformationally restricted analogues of rolipram. The bioassay results demonstrated the oxazolidinone-fused tetrahydroisoquinoline derivatives exhibited moderate to good inhibitory activity against PDE4B and high selectivity for PDE4B/PDE4D. Among these derivatives, compound 12 showed both the strongest inhibition activity (IC 50 = 0.60 μM) as well as good selectivity against PDE4B and good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary SAR study showed that restricting the conformation of the catechol moiety in rolipram with the scaffold of oxazolidinone-fused tetrahydroisoquinoline could lead to an increase in selectivity for PDE4B over PDE4D, which was consistent with the observed docking simulation. [ABSTRACT FROM AUTHOR]

Chromium(salphen) complex 10 is found to be a catalyst for the preparation of oxazolidinones from epoxides and isocyanates. Using the optimal reaction conditions (1.5 mol % of chromium(salphen) complex 10 at 80 °C in toluene for 4 hours), six epoxides were reacted with five isocyanates, providing 15 oxazolidinones in up to 90 % yield. With electron-deficient isocyanates, cyclotrimerisation of the isocyanate to the corresponding isocyanurates is a competing reaction, showing the importance of matching catalyst activity to that of the substrates. [ABSTRACT FROM AUTHOR]

In the present study, we report the fabrication and characterization of novel acetate-based butylimidazolium ionic liquid immobilized silica-coated magnetic nanoparticles (IL-OAc@FSMNP). The synthesized nanocomposite proves its supremacy as an environmentally benign catalyst in the reaction of aniline and its derivatives with ethylene carbonate to form bioactive N-aryl oxazolidin-2-ones under metal-, ligand-, and solvent-free conditions. The catalyst offers excellent assemblies of hydrogen-bond donors and acceptors, which activate the substrates, thereby delivering good-to-excellent product yields with a conversion and selectivity of more than 99%. Additionally, mild reaction conditions, wide substrate scope, effortless catalytic recovery and recyclability of the catalyst up to eight consecutive cycles offer the potential for scale-up in various pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Radezolid (RAD, 12), biaryl oxazolidinone, was synthesised with small modifications according to the methods described in the literature. The pharmacological activity is observed only for (S)-enantiomer, therefore its synthesis is oriented towards obtaining a single isomer of required purity and desired optical configuration. The intermediate products of RAD synthesis were characterised using 1H- and 13C-NMR, as well as the 2D correlation HSQC and HMBC (2, 5, 9, 10), furthermore studied using infrared radiation (FT-IR), Raman scattering (3, 5, 9), and electronic circular dichroism (ECD) (5, 12) spectroscopy. Each technique provides a unique and specific set of information. Hence, the full spectral characteristics of key intermediates obtained from the chiral pool synthesis to the finished product of RAD were summarised and compared. For a more accurate analysis, and due to the lack of reliable and reproducible reference standards for intermediate products, their vibrational analysis was supported by quantum chemical calculations based on the density functional theory (DFT) utilising the B3LYP hybrid functional and the 6-311G(d,p) basis set. Good agreement was observed between the empirical and theoretical spectra. [ABSTRACT FROM AUTHOR]

A novel synthetic pathway towards the 2-oxazolidinone derivatives involving the halo-induced cyclisation of tert -butyl allyl(phenyl)carbamate was successfully developed. Various halogenating reagents were evaluated under different reaction conditions for the reaction optimisation. Interestingly, the synthetic route to 2-oxazolidinone derivatives containing one halogen atom in the aliphatic site or two halogen atoms including the extra halogen atom substituted in the aryl group at the para position, were thoroughly established for all chloro-, bromo- and iodo compounds. Either halo-unsubstituted-aryl oxazolidinone or p -halo-substituted-aryl oxazolidinone could be selectively produced by selecting the appropriate choices of halogenated reagents and reaction conditions e.g. reaction time and temperature. Toloxatone, a commercial antidepressant, was successfully synthesized by using this developed method. [ABSTRACT FROM AUTHOR]

Chemical conversion of CO2 under atmospheric pressure and metal-free conditions remains a great challenge. In this work, a series of alkanolamines, low-cost and biodegradable bases, were used to catalyze the carboxylative cyclization of propargylic amines with CO2. Among these alkanolamines, triethanolamine (TEOA) was found to be a highly efficient organocatalyst for this important transformation at atmospheric pressure, and a series of desired products were synthesized in good to excellent yields. After the reactions, TEOA could be easily recovered and reused without obvious reduction in the efficiency. DFT studies revealed that TEOA may activate CO2 to form a ring-shaped carbonate intermediate that plays an important role in the catalysis of the reaction. This finding provides an effective and environmentally friendly alternative route for the production of 2-oxazolidinones. [ABSTRACT FROM AUTHOR]

This review article surveys literature methods for the carboxylative cyclization of N -propargylamines with CO 2 to provide 2-oxazolidinones. We have classified these reactions based on the type of catalysts. [ABSTRACT FROM AUTHOR]

A organocatalytic system based on economical and readily available cyanuric acid has been developed for the synthesis of 2-oxazolidinones and quinazoline-2,4(1 H,3 H)-diones from propargylamines and 2-aminobenzonitriles under atmospheric pressure carbon dioxide. Notably, a low concentration of carbon dioxide in air was directly converted into 2-oxazolidinone in excellent yields without an external base. Through mechanistic investigation by in situ FTIR spectroscopy, cyanuric acid was demonstrated to be an efficient catalyst for carbon dioxide fixation. [ABSTRACT FROM AUTHOR]

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC90s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistant S. aureus (LRSA) strains (range 2-4 mg/L). The results of the time-kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptible Staphylococcus aureus MSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci. [ABSTRACT FROM AUTHOR]

The article discusses synthesis of rivaroxaban through the synthesis of 5-(S)-aminomethyl oxazolidinone 3, highlighting impurities of rivaroxaban; their mode of formation during preparation; and its use in the prevention of venous thromboembolism after total hip or knee replacement surgery.

In order to address the current downturn in the drug discovery pipeline, initiatives are being undertaken to synthesise screening libraries of sp 3 -rich, low molecular weight compounds. As part of the European Lead Factory initiative, the synthesis and derivatisation of a simple hexahydrooxazolo[5,4- c ]pyridin-2(1 H )-one bicyclic carbamate has been achieved. The synthetic route employed involved a telescoped hetero-Diels–Alder/[2,3]-sigmatropic rearrangement/cyclisation sequence to deliver the desired core scaffold containing two points for further diversification. When applied, this synthesis was found to be robust and scalable which allowed the production of a 155 compound library. [ABSTRACT FROM AUTHOR]

The first broad-spectrum antibiotic chloramphenicol and one of the newest clinically important antibacterials, linezolid, inhibit protein synthesis by targeting the peptidyl transferase center of the bacterial ribosome. Because antibiotic binding should prevent the placement of aminoacyl-tRNA in the catalytic site, it is commonly assumed that these drugs are universal inhibitors of peptidyl transfer and should readily block the formation of every peptide bond. However, our in vitro experiments showed that chloramphenicol and linezolid stall ribosomes at specific mRNA locations. Treatment of bacterial cells with high concentrations of these antibiotics leads to preferential arrest of translation at defined sites, resulting in redistribution of the ribosomes on mRNA. Antibiotic-mediated inhibition of protein synthesis is most efficient when the nascent peptide in the ribosome carries an alanine residue and, to a lesser extent, serine or threonine in its penultimate position. In contrast, the inhibitory action of the drugs is counteracted by glycine when it is either at the nascent-chain C terminus or at the incoming aminoacyl-tRNA. The context-specific action of chloramphenicol illuminates the operation of the mechanism of inducible resistance that relies on programmed drug-induced translation arrest. In addition, our findings expose the functional interplay between the nascent chain and the peptidyl transferase center. [ABSTRACT FROM AUTHOR]

A novel gold(I)-containing ionic liquid-based KCC-1 catalyst was applied for the of propargylic amines with CO2 to provide 2-oxazolidinones. High and ease of recovery from the reaction mixture using an external magnet, and several recycle runs without significant loss in performance are additional eco-friendly attributes of this catalytic system. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]