Oxazolidinones Antibiotics, Chemistry, Applications and Role in COVID-19 Treatment

Oxazolidinones are groups of synthetic antimicrobial agents, which have a novel chemical structure. Their mechanism of antimicrobial mainly bacteriostatic via inhibition of protein synthesis. Oxazolidinones are used in serious cases of bacterial infections. Their spectrum of action against a lot of microbes, which often infect humans vigorously, like penicillin and cephalosporin-resistant Streptococcus pneumonia, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Oxazolidinones chemical structure possesses a ring called oxazolidone, which is characterized by the S configuration of the substituent at C5, the acyl-amino-methyl group connected to C5 and the N-aryl substituent. Some oxazolidinones like linezolid were believed to have a role in COVID-19 treatment. It is also noticed that oxazolidinones have a role in improving clinical status of patients with COVID-19 and in decreasing the risk of mortality caused by co-infections. This review was conducted to discuss the chemistry, mechanism, applications and role of oxazolidinones in the treatment of COVID-19.

后基因组时代的抗结核药物靶位

结核病卷土重来和耐多药结核病(MDRTB)的全球蔓延，推动寻找新型抗结核药物的进程。结核分枝杆菌全基因组序列的破译，以及现有一套新的分析潜在药物靶位遗传学和生物信息学工具，对新型抗结核病药物的开发具有重要的价值。

Synthesis and Antibacterial Activity of (S)-5-(Heterocycle Methylene) -3-(3-Fluoro-4-morpholin-4-yl-phenyl)-Oxazolidin-2-one Derivatives

Aim To study the structure-activity relationship of antibacterial oxazolidinone derivatives. Methods Seven （S） -5- （ heterocycle methylene） -3- （3-fluoro-4-morpholin-4-yl-phenyl） -oxazoli- din-2-ones were synthesized by the substitution of （S）-[ 3-（3-fluoro-4-morpholin-4-yl-phenyl）-oxazohdin-2-one-5-yl]-methanol mesylate with some secondary amines and the structures of the product were confirmed by ^1H NMR and elemental analyses or MS. Results None of the seven compounds showed potent activity against the tested 20 strains of bacteria in vitro. Conclusion The replacement of 5- acetylaminometyl of Linezolid by 5-（heterocycle methylene） lost the antibacterial activity.

A New and Efficient Synthetic Method and Antibacterial Activities of Oxazolidinone Analogues

A series of novel oxazolidinone analogues were prepared by a new and efficient synthetic method and their antibacterial activities were determined. These compounds were characterized by LC-MS and 1H NMR.

Synthesis and Antibacterial Activity of Novel Oxazolidinone Analogs Containing Substituted Thiazole/Fused-Bicyclic Groups

Sixteen novel oxazolidinone analogs containing substituted thiazole/fused-bicyclic（imidazo[ 1,2-b] pyridazine/ imidazo[2,1-b] thiazole） groups were designed and synthesized. A new method for the preparation of the key intermediate compound 11 was proposed. The structures of the target compounds were confirmed by ^1H NMR, IR and MS, and their in vitro antibacterial activities against staphylococcus aureus were evaluated. Among them, compound 16a displays a promising antibacterial activity comparable to that of linezolid.

Synthesis,Crystal Structure and Anticoagulant Activity of 5-Chloro-N-[[(5S)-2-oxo-3-[4-(2-oxopyridin-1(2H)-yl)phenyl]oxazolidin-5-yl]methyl]thiophene-2-carboxamide

The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900（12）, b = 13.086（3）, c = 12.889（3） A, β= 100.86（3）°, V = 959.1（3） ）k3, Z = 2, Dc= 1.489 g/cm3, F（000） = 444,μ= 0.342 mm-l, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections （I 〉 20（I）. The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.

Relative Stability of the Key Enamine,Oxazolidinone,and Imine Intermediates in Some Proline-catalyzed Asymmetric Reactions

Many proline-catalyzed asymmetric addition reactions with ketones as substrates were assumed to involve a key intermediate, an enamine, produced by the condensation of proline and ketone. In this paper, the key intermediate enamines derived from L-proline and cyclohexanone （or acetone） as well as the corresponding oxazolidinone and imine tautomers have been investigated by means of density functional calculations at the B3LYP/6-311＋G^＊＊ level. The predicted order of stability for these tautomers is oxazolidinones 〉 enamines 〉 imines in gas phase and oxazolidinones 〉 imines 〉 enamines in aprotic THF solvent. This prediction explains why enamine intermediate can not be observed experimentally. The predicted energy/enthalpy difference between the formal oxazolidinone structure and the zwitterionic imine structures is very small in THF solvent, suggesting the oxazolidinone-to-imine tautomerization can be readily induced in solvent. ^13C NMR chemical shifts of the oxazolidinone and imine structures have been computed and used to explain the experimental NMR spectra observed in oxazolidinone-to-imine tautomerization induced by protic solvent.

Synthesis and Crystal Structure of 1′-Methyl-4′- (4-chlorophenyl)-1H-indole-3-spiro-2′-pyrrolidine- 3′-spiro-4''-(2''-phenyloxazole)-2,5''(3H,4''H)-dione

The title compound （C26H20ClN3O3） has been synthesized by 1,3-dipolar cycloaddition reaction from isatin, sarcosine and （Z）-4-（4-chlorobenzylidene）-2-phenyloxazol-5（4H）-one through a one-pot procedure, and its structure was confirmed by IR, IH NMR, elemental analysis and single-crystal X-ray diffraction analysis. The crystal belongs to the triclinic system, space group PI, with a = 9.3903（19）, b = 11.398（2）, c = 12.603（3） A, α = 83.495（3）, β = 68.988（3）, γ = 67.178（3）^o, V= 1160.1（4）A^3 Z = 2, Mr= 457.90, Dc= 1.311 g/cm^3, p = 0.198 mm ^-1, F（000） = 476, the final R = 0.0489 and wR = 0.1144 for 3109 observed reflections with I 〉 2σ（I）.

Stable metal-organic frameworks with high catalytic performance in the cycloaddition of CO_2 with aziridines

Based on the mixed ligands XN(4′-(4-pyridine)4,2′:2′,4′′-terpyridine) and isophthalic acid(IPA), three new metal-organic frameworks(MOFs) {[M_2(XN)_2(IPA)_2]·2 H_2O}_n(M=Co(1), Mn(2), Ni(3)) were assembled and structurally characterized,presenting 3 D pillar-chain feature structures. Stability measurements demonstrate that these compounds possess high thermostability and can endure different organic solvents as well as various acid/base solutions with pH range of 1 to 14. Importantly,compounds 1–3 can serve as high-efficiency catalysts for the transformation of CO_2 and aziridines to form high-value oxazolidinones under mild conditions, exhibiting excellent cyclicity at least five times.

The synthesis and antibacterial activity evaluation of oxazolidinone-deferasirox conjugates

We reported herein the synthesis and antibacterial activity evaluation of two oxazolidinone-deferasirox conjugates with different linkers that were designed based on the“Trojan horse”strategy.The conjugates could combine with Fe^(3+)ions as the deferasirox.However,both conjugates were inactive against tested bacteria,including S.aureus,E.coli,A.baumannii,and P.aeruginosa.The results suggested that the synthesized iron chelator deferasirox was not suitable as a siderophore of the bacteria to transport the antibiotic,or the coupling linker of the synthesized conjugates could not be hydrolyzed to release the oxazolidinone in the cytoplasm.Therefore,the design and synthesis of oxazolidinone-deferasirox conjugates need further exploration.

Synthesis and Antibacterial Activity of Oxazolidinone Derivatives Containing Nitro Heteroaromatic Moiety

A series of novel oxazolidinone derivatives containing nitro heteroaromatic moiety was synthesized and characterized by means of ^1H NMR and MS spectra. All target compounds were evaluated for their in vitro antibacterial activities against S.au 29213, methicillin-resistant Staphylococcus aureus（MRSA） and vancomycin-resistant Enterococcus（VRE） by minimum inhibitory concentration（MIC） assay. Most of them exhibited antibacterial activity against S. au 29213, MRSA and VRE. Among them, compounds 10e and 10f displayed better activity than the control.

Asymmetric Synthesis of All Four Isomers of an Unusual Heterocycle-Containing Amino Acid ： 2-Amino-3-furan-2-yl-pentanoic Acid

All four isomers of a novel fl-branched unusual amino acid were designed and synthesized with high stereoselectivity （〉 90% de） and in 33%--44% overall yields by the use of 4（R/S）-5,5-dimethyl-4-phenyl-oxazolidin-2-one as the chiral auxiliary via asymmetric 1,4-Michael addition, direct or indirect azidation, hydrolysis and hydrogenation reactions.