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A diastereoselective (3 + 2) cycloaddition of N-sulfonyl ketimines with vinylethylene carbonates (VECs) in the presence of Pd2dba3·CHCl3 and PPh3 has been developed. The reaction of various substituted VECs and diverse cyclic N-sulfonyl ketimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to excellent yields with moderate to good diastereoselectivities. With the use of spiroketal-based diphosphine SKP as a chiral ligand, an asymmetric version of the current (3 + 2) cycloaddition was achieved, and chiral products were obtained in >99% ee in most cases.

A highly efficient regio- and stereoselective spontaneous formal [3 + 2]-cycloaddition of CO2 in aqueous medium is developed for the one-pot synthesis of spiro[indoline-3,5′-oxazolidine]-2,2′-dione...

Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

Herein we describe the PhI(OAc)2-mediated 1,1- and 1,2-difunctionalization of alkenes with N-tosyl amino alcohols to form oxazolidine and morpholine derivatives. This transformation was realized under mild reaction conditions and allows application to various substrates furnishing the multi-substituted oxazolidines and morpholines with yields up to 98%. A deuterium-labeling experiment was carried out and the result indicated that a phenyl group migration occurred to generate oxazolidine products.

An efficient palladium-catalyzed reaction of N-propargyl oxazolidines for the construction of 4-substituted isoquinolines under microwave irradiation is developed. This transformation proceeds through a sequential palladium-catalyzed reductive cyclization/ring-opening/aromatization cascade via C-O and C-N bond cleavages of the oxazolidine ring. The practical value of this method has also been explored by conducting a millimole-scale reaction, as well as by transforming the isoquinoline into a key intermediate for the synthesis of a lamellarin analogue.

The stereoconvergent synthesis of N-Boc-(2R,3S)-3-hydroxy-2-phenylpiperidine from (R)-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)piperidin-2-one is described. The key steps involved are α-hydroxylation of quiral lactam with O2, stereoconvergent reduction of (R)- or (S)-3-(benzyloxy)-piperidin-2-one with Red-Al® which afforded in both cases the trans-bicyclic oxazolidine in high stereoselectivity after chromatographic purification and a stereospecific Grignard addition to chiral bicyclic oxazolidine.

A straightforward synthesis of enantiopure α-trifluoromethyl aziridine-2-carboxylic acid (α-TfmAzy) is reported from a trifluoropyruvate derived enantiopure oxazolidine. A key Strecker-type synthetic step and a late cyanide basic hydrolysis gave the target compounds in six steps and 41% yield. A final peptide coupling was performed to demonstrate the usefulness of this highly constrained fluorinated unnatural amino acid.

DBU mediated 5-exo-dig cyclization of isothiocyanate and propargyl alcohol leading to valuable heterocyclic compounds has been accomplished. The different modes of nucleophilicity (either S-selective or N-selective) of isothiocyanates were found to depend on the substitution pattern of propargyl alcohol. The terminal propargyl alcohol and isothiocyanate underwent an N-nucleophilic attack to afford 3-substituted 4-methylene oxazolidine-2-thiones. In contrast, exclusive S-nucleophilic cyclization was observed with internal propargyl alcohol to produce (Z)-1,3-oxathiol-2-ylidenes and (Z)-N-(Z)-4-ethylidene-1,3-oxathiolan-2-ylidenes from secondary and primary propargyl alcohols, respectively. The formation of high Z-selectivity in the imine motif and alkene is the highlight of this new method as multiple selectivities over C[double bond, length as m-dash]N and C[double bond, length as m-dash]C in a single system are synthetically highly challenging. The Z-selectivity in imine and alkene may be attributed to electronic and steric factors respectively.

The objective of this paper was to investigate the protective effect of three potential herbicide safeners (3-dichloroacetyl oxazolidine and its two optical isomers) on detoxifying to chloroacetanilide herbicide acetochlor in maize. In this study, physiological and biochemical tests were conducted under laboratory condition in 2015. All safeners increased the expression levels of herbicide detoxifying enzymes, including glutathione S-transferases (GST), catalase (CAT) and peroxidase (POD) to reduce chloroacetanilide herbicide phytotoxicity in maize seedlings. Our results suggest that the R-isomer of R-29148 can induce glutathione (GSH) expression, GST activity, and affinity for the 1-chloro2,4-dinitrobenzene (CDNB) substrate in maize, which can protect maize from injury by chloroacetanilide herbicide acetochlor. Further information on the chiral safener role in antioxida

Classic acetyl thioester protection/deprotection methodologies are widely used in organic synthesis, but deprotection step usually requires harsh conditions not suitable for labile substrates. In this work, a new method for thioester deprotection using a thiotransesterification approach is described. Firstly, thioglycolic acid (TGA) was identified as a good deprotecting reagent in solution. In order to develop a thiol polymer-supported reagent, TGA was anchored to a PEG-based resin through an amide bond (TG-NCO-SH). Both homogeneous and heterogeneous approaches were conveniently carried out at room temperature, in aqueous buffer at pH 8. The mild conditions were suitable for alkyl and phenyl thioesters. Moreover labile thioesters containing thiazolidine and oxazolidine scaffolds, bearing amine, ester and acetal functionalities were also deprotected. The polymer-supported TGA gave better deprotection yields compared to TGA in solution, yields ranging from 61 to 90%. The feasibility of the recovery and reuse of TG-NCO-SH reagent was explored, showing it can be reused at least five times without lossing the activity.

A short and efficient strategy for the synthesis of (−)-cytoxazone, (−)-4- epi -cyoxazone and their analogues by using DDQ mediated diastereoselective intermolecular benzylic amination has been described. Immunological evaluation of their cytokine modulating activity revealed that the change of hydroxy methyl to methyl group increased the cellular immunity in in-vitro cultures. Changes in the stereochemistry of oxazolidine haven't influenced the biological activity.

Pyrrolobenzodiazepines (PBDs) and their dimers (bis-PBDs) have emerged as some of the most potent chemotherapeutic compounds and are currently under development as novel payloads in antibody-drug conjugates (ADCs). However, when used as stand-alone therapeutics or as warheads for small molecule drug conjugates (SMDCs), dose-limiting toxicities are often observed. As an elegant solution to this inherent problem, we designed and synthesized a diazepine-ring-opened bis-PBD prodrug (pro-PBD-PBD) folate conjugate lacking the one of the two imine moieties found in the corresponding free bis-PBD. Upon entering a targeted cell, cleavage of the linker system, including the hydrolysis of an oxazolidine moiety, results in the formation of a reactive intermediate which possesses a newly formed aldehyde as well as an aromatic amine. A fast and spontaneous intramolecular ring-closing reaction subsequently takes place as the aromatic amine adds to the aldehyde with the loss of water to give the imine, and as a result, the diazepine ring, thereby delivering the bis-PBD to the targeted cell. The in vitro and in vivo activity of this conjugate has been evaluated on folate receptor positive KB cells. Sub-nanomolar activity with good specificity and high cure rates with minimal toxicity have been observed.

International audience; Combining different molecular switching functions in a single molecule is a simple strategy to develop commutable molecules featuring more than two commutation states. The present study reports on two molecular systems consisting of two indolino-oxazolidine (Box) moieties connected to an aromatic bridge (phenyl or bithiophene) by ethylenic junctions. Such systems, referenced as BiBox, are expected to show up multiaddressable and multiresponsive behaviors. On one hand, the oxazolidine ring opening/closure of Box moieties can be addressed by chemical stimuli, and on the other hand, the trans-to-cis isomerization of the ethylenic junctions is induced by visible light irradiation (with a thermal back conversion). NMR and UV−visible spectroscopies allowed to characterize up to nine out of the ten theoretically expected commutation states as well as to measure the kinetics of the interconversions. Also, steady state fluorescence spectroscopy measurements highlighted the strong influence of the open/closed states of the Box moieties on their emission properties.

A novel series of thiourea, carbamimidothioic acid, 4, 5-dihydrooxazole-2-thiol, oxazolidine-2thine, and 2-amino-1-phenylpropyl-2-chloroacetate derivatives was designed and synthesized using 2-amino-1-phenylpropan-1-ol (L-norephedrine) as a strategic starting material. The structures of the newly synthesized compounds were established by elemental analyses, IR, and 1H NMR and 13C NMR spectral data. The compounds were evaluated for their in vitro anticancer activity against various cancer cell lines. The corresponding acetamide, carbamimidothioic acid, and 2-2-amino-1-phenylpropyl-2-chloroacetate derivatives showed almost the same activity as the standard drug doxorubicin against human breast cancer cell line (MCF-7). Also, the acetamide and 2-thioxoimidazolidin-4-one derivatives exhibited higher activity than the reference drug doxorubicin against human colon cancer cell line (HCT 116).

Plasma amine oxidase (PAO), which is also designated as semicarbazide-sensitive amine oxidase (SSAO), copper-containing amine oxidase 3 (AOC3), or vascular adhesion protein-1 (VAP-1), catalyzes the oxidative deamination of primary amines to aldehydes using copper and a quinone as cofactors. Because it participates in the transmigration of inflammatory cells through the blood vessels into the tissue, PAO is attributed an important role in inflammatory diseases. Therefore, inhibitors of this enzyme could lead to new therapeutics for the treatment of inflammation-related conditions. Assays for the evaluation of PAO inhibitors usually measure the conversion of benzylamine to benzaldehyde by UV spectroscopy. We have developed a test system with the new substrate 6-(5-phenyl-2H-tetrazol-2-yl)hexan-1-amine, monitoring the formation of the enzyme product 6-(5-phenyl-2H-tetrazol-2-yl)hexanal by reversed phase HPLC with UV detection. Since this compound only eluted with poor peak shape due to hydrate formation in the aqueous mobile phase, it was derivatized with tris(hydroxymethyl)aminomethane (TRIS) under mild conditions to an oxazolidine prior HPLC analysis. The validation of the method revealed that the new substrate was bound with higher affinity to PAO and converted with higher velocity than the standard substrate benzylamine.

Pyrolysis of azido- meta -meconine yields only a single product 1D, which has been characterized spectroscopically ( 1 H NMR, 13 C NMR, HSQC, DEPT & MS). These results reveal that the fused five-member lactone ring can influence the product selectivity. The DFT calculations suggest the formation of favourable oxazolidine intermediate compared to azirine ( 1Z ) and ketenimine ( 1H ) intermediates. The isodesmic analysis showed that the fused lactone aryl nitrene ( 1N ) would have more strain to form azirine ( 1Z ) intermediate than the corresponding aryl nitrene ( 1M ).

Anthracyclines are a class of antitumor compounds that are successful and widely used but suffer from cardiotoxicity and acquired tumor resistance. Formaldehyde interacts with anthracyclines to enhance antitumor efficacy, bypass resistance mechanisms, improve the therapeutic profile, and change the mechanism of action from a topoisomerase II poison to a DNA cross-linker. Contrary to current dogma, we show that both efficient DNA cross-linking and potent synergy in combination with formaldehyde correlate with the anthracycline's ability to form cyclic formaldehyde conjugates as oxazolidine moieties and that the cyclic conjugates are better cross-linking agents and cytotoxins than acyclic conjugates. We also provide evidence that suggests that the oxazolidine forms in situ, since cotreatment with doxorubicin and formaldehyde is highly cytotoxic to dox-resistant tumor cell lines, and that this benefit is absent in combinations of formaldehyde and epirubicin, which cannot form stable oxazolidines. These results have potential clinical implications in the active field of anthracycline prodrug design and development.

A novel amphiphilic copolymer consisting of tetraphenylethylene-oxazolidine (TPE-OX) as a pH-sensitive chromophore and poly(ethylene glycol) methyl ether methacrylate (PEGMA) as a water-soluble chain has been well designed and synthesized. A self-assembled polymeric micelle based on the copolymer exhibited clear dual-emission switching between cyan and red with a decrease of pH value in Tris-HCl buffer solution due to the extended conjugation and emerging intramolecular charge transfer effect when opening the spiro-ring of OX moiety. Fluorescence imaging of HepG2 cells stained by the polymeric micelle shows switched luminescence from cyan to red with high selectivity and contrast, indicating that the polymeric micelle was an effective probe for intracellular pH detection. Additionally, the red emission of the polymeric micelle in lysosomes can reversibly switch back to the original cyan emission in response to the two lysosomal activity inhibitors chloroquine and bafilomycin, which demonstrates that the polymeric micelle has potential applications in detecting the activity of lysosomal and further autophagy in cancer cells.

Targeting of protein tyrosine phosphatase-1B (PTP1B) has emerged as a promising strategy for therapeutic intervention of diabetes and obesity. Investigation of new inhibitors with good bioavailability and high selectivity is the major challenge of drug discovery program targeting PTP1B. Therefore, herein, new neutral benzene-sulfonamide containing compounds were designed, synthesized and biologically evaluated as potent PTP1B inhibitors. New series of thiazolidine, oxazolidine, thiazinan, oxazinan, oxazole, thiazole, tetrazole, cyanopyridine, chromenone, and iminochromene of benzene-sulfonamide derivatives (MSE-1 to MSE-15) were synthesized in a good yield under mild condition using sulfadiazine as a starting material. Among the synthesized compounds, MSE-13 and MSE-14 showed the most in vitro potent PTP-1B inhibitory activity (IC50 of 0.88 µM and 3.33 µM, respectively). Animal treatment by the target compounds significantly improved the insulin resistance, diminished plasma glucose level, decreased initial body weight, and normalized the serum lipid profile compared to pioglitazone, a standard PTP1B inhibitor. The molecular modeling study showed a high affinity and selectivity of our synthesized compounds to the active site and B-site of PTP1B holding hydrogen bonding, hydrophobic, and electrostatic interactions. Furthermore, Electrostatic Surface Potential (ESP) and HOMO/LUMO analysis indicated the importance of sulfamoyl moiety for PTP1B binding. In silico ADME predictions of such compounds also showed the promising pharmacokinetic and physicochemical properties. The proposed compounds could be considered a lead inhibitory scaffold to PTP1B.

[EN] A simple and effective colorimetric method for the detection of normetanephrine (NMN), an O-methylated metabolite of norepinephrine, using functionalised gold nanoparticles is described. This metabolite is an important biomarker in the diagnosis of adrenal tumours such as pheocromocytoma or paraganglioma. The colorimetric probe consists of spherical gold nanoparticles (AuNPs) functionalised with two different ligands, which specifically recognize different functional groups in normetanephrine. Thus, a benzaldehyde-terminated ligand was used for the recognition of the amino alcohol moiety in NMN, by forming the corresponding oxazolidine. On the other hand, N-acetyl-cysteine was chosen for the recognition of the phenolic hydroxyl group through the formation of hydrogen bonds. The selective double molecular recognition between the probe and the hydroxyl and the amino-alcohol moieties of normetanephrine led to interparticle-crosslinking aggregation resulting in a change in the color of the solution, from red to blue, which could be observed by naked eye. The probe was highly selective towards normetanephrine and no color changes were observed in the presence of other neurotransmitter metabolites such as homovanillic acid (HVA) (dopamine metabolite), 5-hydroxyindoleacetic acid (5-HIAA) (serotonin metabolite), or other biomolecules present in urine such as glucose (Glc), uric acid (U.A), and urea. Finally, the probe was evaluated in synthetic urine with constituents that mimic human urine, where a limit of detection of 0.5 mu M was achieved., Financial support from the Spanish Government (project MAT2015-64139-C4) and Generalitat Valenciana (Project PROMETEOII/2014/047 and AICO/2017/093) is gratefully acknowledged. T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisolia fellowship.

A dual catalytic system, dirhodium tetrapivalate/ytterbium(III) triflate, enables the three-component reactions of α-alkyl-α-diazoesters, aromatic aldehydes, and N-benzylidenebenzylamine derivatives to afford the corresponding β-amino alcohols in good yields after hydrolysis of the oxazolidine cycloadducts, whereas no β-amino alcohols are obtained in the absence of ytterbium(III) triflate. A similar dual catalytic system, dirhodium tetraacetate/ytterbium(III) triflate, is found to be effective in accelerating the reactions of α-aryl-α-diazoesters in high yields. Furthermore, the reactions using dimethyl diazomalonate are described.

A novel and efficient microwave-assisted protocol to 1,4-diheterocycle-2-butynes was successfully developed. The method is based on one-pot copper-catalyzed A 3 reaction/decarboxylative coupling of a propiolic acid, a formaldehyde, and a 1,2- or 1,3-amino alcohol. This multicomponent coupling reaction provides a straight forward access to introduction oxazolidine or 1,3-oxazinane at the 1,4-position of a but-2-yne from readily available starting materials. 1,4-Diheterocycle-2-butynes with diverse substitution patterns are obtained in moderate to good yields.

A versatile, operationally simple and highly efficient one-pot three-component approach for the synthesis of spiro oxazolidine oxindole derivatives has been developed by the domino reaction of isatins, arylacetylenes, and N -tosyl aldimines in acetonitrile catalyzed by InBr 3 at ambient temperature. The significant advantages of this protocol are highlighted by excellent yields, cleaner reaction profiles, avoidance of toxic catalyst, broader substrate scope, and successful assembly of three new C–C, C–N and C–O bonds.

A new development in the palladium-catalyzed allylation reaction of trifluoromethylated ketene aminoacetals was reported. These nucleophilic reagents were prepared by adding aminoalcohols to methyl 3,3,3-trifluoro-2-trifluoromethylpropanoate. The asymmetric version of the allylation reaction was investigated using chiral oxazolidine-based starting materials or chiral palladium catalysts. Asymmetric allylic alkylation was carried out with up to 74% ee using a chiral catalyst. However, no improvement was observed using double stereodifferentiation. These results provided a novel access for trifluoromethylated all-carbon quaternary carbon centers.

In this work, the synthesis of a new class of trans-oxazolidines by the regio- and stereocontrolled reaction of NH-ketoaziridines with phenylisocyanate is reported. A plausible mechanism has been proposed.

A controlled and facile synthesis of various glycosyl 1,3-oxazolidine-2-thiones and 1,3- thiozolidine-2-thiones has been accomplished from corresponding sugar azido alcohols utilizing Staudinger reaction (PPh3 and CS2) via isothiocynate route. A series of reactions were performed to investigate the effects of CS2 and PPh3 on the selectivity of product formed. The excessive addition of CS2 with PPh3(1.2 equiv) afforded oxazolidine-2-thione alone, while the solitary addition of PPh3 for 30 min followed by addition of CS2 to the reaction mixture resulted both the products in different ratios, which were successfully isolated using column chromatography (SiO2). Furthermore, synthesis of 1,3-oxathiolan-2-imine from glycosyl epoxide has also been attempted. Structures of all the developed compounds have been elucidated using extensive spectroscopic techniques including IR, NMR and MS analysis.

Safeners are important tools used to ensure to safe useof herbicide. The aim of this paper is to evaluate the protective effect of four safeners (R-28725, 3-dichloroacetyl oxazolidine and its two optical isomers) and investigate the mechanism of herbicide detoxication by safener. Laboratory studies were conducted to evaluate the effectiveness of safeners for protecting maize from the residues of preemergent herbicide fomesafen in Northeast Agricultural University, China. Physiological and biochemical tests were herein conducted under laboratory conditions, by using seed treatment with safeners and soil treatment with fomesafen, respectively. R-28725 provoked high glutathione level, glutathione-Stransferase activity and affinity of glutathione-S-transferase than other safeners, but R-isomer treatment resulted in complete reversal of injury caused by fomesafen.&nbsp

We have previously reported on a study of the structure–activity relationship in a series of 2,3,4-substituted oxazolidines recently discovered by our group varying the substituent at the ring or stereochemistry of the oxazolidine ring. We discovered the cytotoxic and pro-apoptotic potential of compounds 1 and 2 with good selectivity against cancer cell lines. In the present study we describe the synthesis and cytotoxic evaluation against cancer cell lines (HL60, JURKAT, MDA-MB-231 and LNCaP) of a series of oxazolidines designed by isosteric replacement or rigidification of the oxymethylene spacer of compounds 1 and 2. Alkenes 3 and 4 retained the activity against MDA-MB-231 cells and they were more active on HL60, JURKAT and LNCaP cells. Considering LNCaP cells, E-isomer 4 was at least 7 times and about 3 times more potent than lead 1 and Z-isomer 3, respectively. Compound 4 exerted significant activity against LNCaP with IC50 in the low micromolar range (11 μM) without affecting VERO cells and PBMC proliferation (IC50 > 100 μM) indicating its low toxicity to normal cells.

A facile and catalytic asymmetric synthesis of the pentacyclic core of (-)-nakadomarin A, containing all the stereogenic centers of the natural product was achieved. The key intermediate involves the oxazolidine moiety as an iminium cation equivalent. An efficient method for the removal of the N-hydroxyethyl group is also described.

A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines, derived from (R*, S*)-(±)-mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 μg/mL. In general compounds with aryl groups having strong electron-releasing substituents, such as HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are active. However, other factors such as steric effects may play a role. As both the active and non-active conformations of the mefloquine-oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.

Phenyl oxazolidinones were prepared from R - glycidyl butarate and Para bromo aniline, further (3 - (4 - bromophenyl) methylene oxazolidine - 5yl) and substituted benzothiazinen was refluxed resulted in oxazoli dinones benzothiazinen moieties. Treatment of these oxazolidinones benzo thiazinen moieties with methane sulfonyl gives its sulphonates on further treatment with sodium azide and tri phenyl phosphine in acetic anhydride gives acetamide derivatives . Further synthesized compounds were characterized by IR, H NMR 1 and Mass spectral studies. T he synthesized compounds were evaluated for antibacterial activity against Bacillus subtilis , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa and antifungal activity against , Candida albicans and Aspergillus

An expedient regio-, stereo- and product-selective synthesis of novel hybrid heterocyclic systems comprising [1,2-c]oxazolidine, pyrrolidine and piperidine units, in good to excellent yields, has been developed via three-component 1,3-dipolar cycloaddition/annulation domino reactions and concomitant trifluoroacetic acid mediated condensative annulation with paraformaldehyde. These novel structurally complex heterocyclic hybrids, accessed by a two-step protocol, possess seven rings and seven contiguous stereocentres.

A convenient one-pot method for the preparation of (4Z)-4-(arylmethylidene)-5-ethoxy-1,3-oxazolidine-2-thiones 2 and 3 from ethyl (2Z)-3-aryl-2-isothiocyanatoprop-2-enoates 1, which can be easily prepared from ethyl 2-azidoacetate and aromatic aldehydes, has been developed. Thus, these α-isothiocyanato α,β-unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5-substituted (4Z)-4-(arylmethylidene)-5-ethoxy-1,3-oxazolidine-2-thiones, 2, and 2-[(4Z)-(4-arylmethylidene)-5-ethoxy-2-thioxo-1,3-oxazolidin-5-yl]acetates, 3.

Chemoselective Dieckmann cyclization reactions may be used on oxazolidine and thiazolidine templates derived from various aldehydes to access bicyclic tetramates, which have potential as templates for chemical library construction. Bioassay against Staphylococcus aureus and Escherichia coli showed that these systems have little or no intrinsic antibacterial bioactivity.

The synthesis of substituted [4.3.0] bicyclic lactams derived from 6-oxo-2-hydroxymethylpiperidine is described. The enolate derived from these systems can be alkylated with a range of reactive electrophiles; the diastereoselectivity which can be achieved depends on the substitution pattern of the oxazolidine ring system and the nature of the alkylating reagent, and can vary from 1:1 to as much as 10:1.

A novel iron-catalyzed synthesis of substituted N-aryl oxazolidines was developed via C–N bond formation and methylenation. The reaction of aryl hydroxylamines with allyl alcohols, in the presence of formaldehyde or its equivalents, afforded variety of oxazolidine heterocycles in very good yields. This catalytic method is most effective for para-substituted aryl hydroxylamines and 3-methyl allyl alcohols. Furthermore, acid catalyzed demethylenation of oxazolidines allowed access to N-aryl amino alcohols in good yields.

1.The first generation 5HT-4 partial agonist, 4-{4-[4-Tetrahydrofuran-3-yloxy)-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol, PF-4995274 (TBPT), was metabolized to N-dealkylated (M1) and an unusual, cyclized oxazolidine (M2) metabolites. M1 and M2 demonstrated pharmacological activity at 5HT receptor subtypes warranting further investigation into their dispositional properties in humans; M2 was a minor component in vitro but was the pre-dominant metabolite identified in human plasma. 2.To shift metabolism away from the piperidine ring of TBPT, a series of heterocyclic replacements were designed, synthesized, and profiled. Groups including azetidines, pyrrolidines, as well as functionalized piperidines were evaluated with the goal of identifying an alternative group that maintained the desired potency, functional activity, and reduced turnover in human hepatocytes. 3.Activities of 4-substituted piperidines or pyrrolidine analogs at the pharmacological target were not significantly altered, but the same metabolic pathways of N-dealkylation and oxazolidine formation were still observed. Altering these to bridged ring systems lowered oxazolidine metabolite formation, but not N-dealkylation. 4.The effort concluded with identification of azetidines as second-generation 5HT4 partial agonists. These were neither metabolized via N-dealkylation nor converted to cyclized oxazolidine metabolites rather oxidized on the isoxazole ring. The use of azetidine as a replacement for aliphatic aza-heterocyclic rings in drug design to alter drug metabolism and pharmacology is discussed.

Substrates bearing electron-withdrawing substituents afford the products with higher enantioselectivities.

Conjugate addition of thiazolidinethiones and oxazolidinethiones to N-crotonylthiazolidinethiones and -oxazolidinethiones was observed in the presence of excess triethylamine in dichloromethane. The addition takes place by the nitrogen of the heterocycle with high diastereoselectivity. It was observed that the stereoselective addition occurs on the anti-s-cis conformation of the N-enoyl sulfur-containing heterocycle.

The alkylation reactions of an amide sodium enolate derived from a C-2 disubstituted trifluoromethylated oxazolidine (Fox) chiral auxiliary occurred in good yields with a very high diastereoselectivity (>98% de). Compared to the C-2 monosubstituted trifluoromethyl analogue, this chiral auxiliary is much more stable towards bases at temperature over −35 °C because the dehydrofluorination reaction is avoided. However asymmetric enolates quaternarization was not successfully achieved with this new chiral auxiliary.

An efficient and stereoselective reaction between 3-isothiocyanato oxindoles and isatins/isatinimines has been developed to afford structurally diverse dispiro[oxazolidine-2-thione]bisoxindoles and dispiro[imidazolidine-2-thione]bisoxindoles in excellent results under mild conditions. The potential of asymmetric induction by means of a chiral auxiliary was explored. The isomers are separable, and products could be isolated as single diastereomers by column chromatography. Further synthetic transformations of the reaction product were also successfully realized.

Selective saturation of the conjugated C–C double bonds in the title compounds was examined in a systematic way for the first time. Many established protocols effective for similar reduction of α,β-unsaturated ketones and esters in the literature were found to be inapplicable in the present context. The most satisfactory results were finally obtained using the DIBAL-H/MeLi/CuI/HMPA/THF conditions.

Jadomycin A and related jadomycin M and W aglycons were synthesized. Easy re-construction of 4-(hydroxymethyl)-1,3-oxazolidin-5-one system into an isomeric 1,3-oxazolidine-4-carboxylic acid system during the synthetic trial of jadomycin S aglycon requests us to more precisely re-examine the structures proposed for jadomycins S and T, derived from hydroxyl-containing amino acids of l -serine and l -threonine, respectively.

The cytochrome bc₁ complex (EC 1.10.2.2, bc₁) is one of the most promising targets for new drugs and agricultural fungicides. Among the existing bc₁ complex inhibitors specifically binding to the Q(o) site, oxazolidinedione derivatives have attracted great attention. With the aim to understand the substituent effects of oxazolidinedione derivatives on the inhibition activity against the bc₁ complex, a series of new oxazolidinedione derivatives were designed, synthesized, and biologically evaluated. The further inhibitory kinetics studies against porcine succinate-cytochrome c reductase (SCR) revealed that the representative compound 8d and famoxadone are both non-competitive inhibitors with respect to the substrate cytochrome c, but competitive inhibitors with respect to substrate decylubiquinol (DBH₂). In addition, compound 8d and famoxadone showed, respectively, 35-fold and 15-fold greater inhibitory activity against the porcine SCR than the porcine bc₁ complex, indicating that these two inhibitors not only inhibited the activity of the bc₁ complex, but possibly affect the interaction between the complex II and the bc₁ complex. To our knowledge, this is the first report that famoxadone and its analogs have effects on the interaction between the complex II and the bc₁ complex.

The drug resistant bacteria pose a severe threat to human health. The increasing resistance of those pathogens to traditional antibacterial therapy renders the identification of new antibacterial agents with novel antibacterial mechanisms an urgent need. In this study, a series of (2S)-N-substituted-1-[(formyhydroxyamino)methyl]-1-oxohexyl]-2-oxazolidinecarboxamides were designed, synthesized and evaluated for in vitro antibacterial activity. Most of these compounds displayed good activities against Gram-positive organisms comparable to reference agent LBM-415.

An easy one-pot, multistep cascade reaction which could afford a series of substituted benzo[d]pyrido[2,1-b]oxazolidine and [1,3]oxazine derivatives in a highly enantio- (up to 98% ee) and diastereoselective (4:1 to >20:1 dr) manner with generally good to excellent yields (up to 99%) has been developed. This well designed strategy could be applied to a wide scope of substrates under mild conditions with simple operations.

A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at 30 °C using a CO(2) balloon in the presence of K(2)CO(3) has been developed, which leads to an efficient assembly of oxazolidine-2,4-diones. It is observed that the regioselectivity was controlled by the aryl group.

A nonstabilized azomethine ylide reacts with a wide range of substituted isatoic anhydrides to afford novel 1,3-benzodiazepin-5-one derivatives, which are generally isolated in high yield. The transformations involve 1,3-dipolar cycloaddition reactions of the ylide with the anhydrides to give transient, and in a representative case spectroscopically observable, oxazolidine intermediates that undergo ring-opening-decarboxylation-ring-closing reaction cascades to yield the 1,3-benzodiazepin-5-one products.

A new approach to the synthesis of 1,3-oxazolidine-2,4-diones, via a two-step reaction sequence, starting from the readily available α-ketols and isocyanates, is reported. The condensation of the latter led to the key precursors 4-methylene-2-oxazolidinones, which are converted into the diones by an oxidative cleavage of the exocyclic double bond. Thus, 5,5-disubstituted 1,3-oxazolidine-2,4-diones can be accessed in good yields from the appropriate functionalized α-ketols. Moreover, two alternative routes are also described either by functionalization of 4-oxazolin-2-ones or by alkylation of the 1,3-oxazolidine-2,4-dione core previously prepared. Upon hydrolysis of the 1,3-oxazolidine-2,4-diones, a series of α-hydroxyamides bearing a quaternary stereocenter were obtained.