Synthesis Of Oxazolidinones Research Articles

Convenient Synthesis of Oxazolidinones and Oxazinones from Allyl and Homoallyl Amines under Mild Conditions

An efficient one‐pot general method for the high‐yield synthesis in solution of oxazolidinones and oxazinones from allyl‐ and homoallylamines, respectively, has been developed. The reaction is carried out at an atmospheric pressure between 0°C and room temperature using a solution of carbon dioxide in acetonitrile and hindered guanidine as the base.

Lipase-mediated resolution of 3-hydroxy-4-trityloxybutanenitrile: synthesis of 2-amino alcohols, oxazolidinones and GABOB

Lipase-mediated kinetic resolution of 3-hydroxy-4-trityloxybutanenitrile gave the ( S)-alcohol and ( R)-acetate in good yields and high enantioselectivities. The resolution using Pseudomonas cepacia lipase ( Burkholderia cepacia) immobilized on modified ceramic particles (PS-C) in diisopropyl ether gave the best results. The use of base additives in this transesterification drastically reduces the reaction time without effecting the yields or enantioselectivities. Resolved 3-hydroxy-4-trityloxybutanenitrile has been utilized for the synthesis of enantiomerically pure 5-tosyloxymethyl-1,3-oxazolidine-2-one, which is an important intermediate for the preparation of β-adrenergic blocking agents and oxazolidinone based antimicrobial agents. Enantiomerically pure ( R)-3-hydroxy-4-trityloxybutanenitrile and ( S)-5-tosyloxymethyl-1,3-oxazolidine-2-one have been utilized in the enantioconvergent synthesis of ( R)-GABOB.

Synthesis of annulated oxazolidinones as potential precursors of cyclic cis-β-amino alcohols

A simple method for the synthesis of annulated 1,3-oxazolidin-2-ones from accessible ketones, acetylene, and carbon dioxide was developed. If their molecules contain arylalkyl substituents, intramolecular cyclization in acidic media gave rise to fused heterocyclic systems in high yields. The effects of the substituents in positions 3 and 5 of the oxazolidine ring on the regioselectivity of this cyclization were studied. The possibilities of converting oxazolidinones into cyclic cis-β-amino alcohols were studied.

Synthesis and SAR of novel oxazolidinones: Discovery of ranbezolid

Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the ‘piperazinyl–phenyl–oxazolidinone’ core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible Gram-positive organisms, along with the identification of ranbezolid ( RBx 7644) as a clinical candidate.

Convenient Synthesis of Oxazolidinones by the Use of Halomethyloxirane, Primary Amine, and Carbonate Salt

[reaction: see text] Primary amines reacted with carbonate salts (Na2CO3, K2CO3, Cs2CO3, and Ag2CO3) and halomethyloxiranes in the presence of a base such as DBU or TEA to give oxazolidinones in high yields. The use of K2CO3 among these carbonate gave the best yield in this synthesis. A reaction mechanism was proposed that the oxazolidinone was obtained from an oxazinanone intermediate via a bicyclo[2.2.1] intermediate. The present reaction can be widely applied to convenient synthesis of useful N-substituted oxazolidinones and chiral oxazolidinones.

Synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones: novel analogs of linezolid

The synthesis and antibacterial activity of oxazolidinones containing dihydro-1,2-oxazine and 2-pyrazoline ring systems are described. Linezolid analogs utilizing dihydro-1,2-oxazines as morpholine mimics were prepared utilizing a nitrosoamine/diene 4+2 cycloaddition strategy. Pyrazolidine, hexahydro-pyridazine, and 2-pyrazoline analogs more closely related to eperezolid were also prepared. The most active of these new oxazolidinones were the dihydro-1,2-oxazine 6 and the 2-pyrazoline 20 both of which had potency similar to linezolid against a panel of Gram-positive bacteria.

Synthesis and antibacterial activity of new N-linked 5-triazolylmethyl oxazolidinones

A new series of N-linked 5-triazolylmethyl oxazolidinones with varying substitution at the piperazine nitrogen 4-position were synthesized and tested against a panel of Gram-positive and Gram-negative bacteria including clinical isolates. Most of the compounds showed excellent antibacterial activity against susceptible and resistant Gram-positive organisms. One of the compounds showed enhanced antibacterial activity against Moraxella catarrhalis.

Synthesis of Oxazolidinones and 1,2‐Diamines from N‐Alkyl Aziridines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring

A series of oxazolidinone derivatives, which morpholino group of linezolid was replaced with heteroaromatic ring substituted pyridine moiety, were newly synthesized, and their substituted effects on in vitro and in vivo antibacterial activities were evaluated against four problematic gram-positive strains including drug resistant strains and two gram-negative strains. Most compounds exhibited the enhanced in vitro activities with 4–16-fold and three compounds exerted more than 2-fold increased in vivo efficacies than linezolid.

(Salen)chromium(III)/DMAP: An Efficient Catalyst System for the Selective Synthesis of 5-Substituted Oxazolidinones from Carbon Dioxide and Aziridines

[reaction: see text] (Salen)chromium(III)/DMAP was found to be an active catalyst system for the coupling of CO(2) and aziridines. The oxazolidinone products were produced in high yield and selectivity from the opening of the aziridine at the most substituted N-C bond. This catalyst system worked well for a wide variety of monosubstituted N-aryl and N-alkyl aziridines as well as a 2,3-disubstituted N-alkyl aziridine.

Solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates.

The first solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates is described. Synthesis of the title compounds was achieved by alkylation of resin-bound carbamates with glycidyl tosylate, followed by cycloaddition of the resulting epoxides with isocyanates at elevated temperature in high yields and purity. Because N-aryloxazolidinones have been known to possess various biological activities, this method is useful from the viewpoint of drug discovery.

Stereoisomeric Synthesis of Oxazolidinone and Fused Pyrrolidine Derivatives via Azomethine Ylides and Their Antimicrobial Activity.

The reaction of isatin with secondary cyclic α-amino acid 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid gives rise to azomethine ylide which undergoes [3+2] cycloaddition with various dipolarophiles to afford inseparable stereoisomeric mixture of spiro oxazolidinone and fused pyrrolidinc derivatives. The newly synthesized compounds have been screened for their antimicrobial activities.

Design, Synthesis and Biological Evaluation of Oxazolidinone–Quinolone Hybrids

Oxazolidinone–quinolone hybrids that combine the pharmacophores of a quinolone and an oxazolidinone were synthesised and shown to be active against a variety of resistant and susceptible Gram-positive and fastidious Gram-negative organisms. The best compounds in this series overcome all types of resistance in relevant clinical Gram-positive pathogens. The nature of the spacer greatly influences the antibacterial activity. The dual mode of action could be demonstrated for compounds having a piperazinyl spacer. Antibacterial activity was higher at acidic pH.

Synthesis of Oxazolidinones by a Solid-Phase/Activation Cycloelimination (SP/ACE) Methodology

A versatile method for the solid-phase synthesis of oxazolidinones is described. An appropriate 1,2-diol is attached to immobilized sulfonyl chloride, resulting in the selective activation of one of the alcohol functions. The subsequent reaction of the other alcohol group with an isocyanate, followed by a base-promoted cycloelimination gives an oxazolidinone. By proper choice of isocyanates, functionalities can be introduced which are essential for antibiotic activity.

Synthesis of N-arylated oxazolidinones via a palladium catalyzed cross coupling reaction. Application to the synthesis of the antibacterial agent Dup-721

A method for the intermolecular coupling of aryl bromides and oxazolidinones is described. Application to intermediates useful for the preparation of a known class of antibacterial agent and the synthesis of the known antibacterial oxazolidinone Dup-721 are described.

Solid phase synthesis of oxazolidinones via a novel cyclisation/cleavage reaction

The solid phase synthesis of oxazolidinones via a novel cylisation/cleavage reaction is described. Resin bound carbamates 2, which were obtained by reaction of Wang-resin with commercially available isocyanates 1, were alkylated with glycidyltosylate to the corresponding epoxides 3. Nucleophilic opening of the epoxides 3 with pyrrolidine and subsequent cyclisation leads to the title compounds in high yield and purity.

Sulfoxide-Mediated Asymmetric Synthesis of Glycosidase Inhibitor Precursors.

The highly diastereoselective DIBALH and DIBALH/ZnBr(2) reduction of enantiomerically pure (5S,(S)S)-3-ethoxy-5-(p-tolylsulfinyl)cyclopentenone (9) is used as a key step to the synthesis of oxazolidinone 2, a precursor of glycosidase inhibitor mannostatin. Compound 9 was obtained from 3-ethoxycyclopentenone by direct sulfinylation with (S)-N-benzyl-N-(p-tolylsulfinyl)propionamide.

ChemInform Abstract: One‐Pot Synthesis of Oxazolidinones by Tosylation or Mesylation of N‐ Boc‐β‐amino Alcohols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A Facile Synthesis of Oxazolidinones via Lanthanide‐Catalyzed Cycloaddition of Epoxides with Isocyanates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Facile Synthesis of Oxazolidinones via Lanthanide-Catalyzed Cycloaddition of Epoxides with Isocyanates

A Facile Synthesis of Oxazolidinones via Lanthanide-Catalyzed Cycloaddition of Epoxides with Isocyanates