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Enantioselective organocatalytic michael addition of nitroalkanes and other nucleophiles to beta-trifluoromethylated acrylamides

An organocatalytic asymmetric Michael addition of nitroalkanes to trifluoromethylated acrylamides in good yields and with good to excellent diastereoselectivities and excellent enantioselectivities is described. The Michael adducts could be readily transformed into optically pure trifluoromethylated gamma-aminobutyric acid 7 in high yields without loss in enantioselectivities.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H1129NO – PubChem

 

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History of antimicrobial drug discovery: Major classes and health impact

The introduction of antibiotics into clinical practice revolutionized the treatment and management of infectious diseases. Before the introduction of antibiotics, these diseases were the leading cause of morbidity and mortality in human populations. This review presents a brief history of discovery of the main antimicrobial classes (arsphenamines, beta-lactams, sulphonamides, polypeptides, aminoglycosides, tetracyclines, amphenicols, lipopeptides, macrolides, oxazolidinones, glycopeptides, streptogramins, ansamycins, quinolones, and lincosamides) that have changed the landscape of contemporary medicine. Given within a historical timeline context, the review discusses how the introduction of certain antimicrobial classes affected the morbidity and mortality rates due to bacterial infectious diseases in human populations. Problems of resistance to antibiotics of different classes are also extensively discussed.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H297NO – PubChem

 

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Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors

Mutant isocitrate dehydrogenase 1 (IDH1) is an attractive therapeutic target for the treatment of various cancers such as AML, glioma, and glioblastoma. We have evaluated 3-pyrimidin-4-yl-oxazolidin-2-ones as mutant IDH1 inhibitors that bind to an allosteric, induced pocket of IDH1R132H. This Letter describes SAR exploration focused on improving both the in vitro and in vivo metabolic stability of the compounds, leading to the identification of 19 as a potent and selective mutant IDH1 inhibitor that has demonstrated brain penetration and excellent oral bioavailability in rodents. In a preclinical patient-derived IDH1 mutant xenograft tumor model study, 19 efficiently inhibited the production of the biomarker 2-HG.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H1207NO – PubChem

 

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Selective preparation of isomers and enantiomers of cyclopropane carboxylic acids

A process has been discovered for selective preparation of isomers and enantiomers of 2,2-dimethyl-3-(2,2-dihalovinyl)cyclopropane carboxylic acids. In this process an adduct of an alkyl 3,3-dimethyl-4-pentenoate and a substituted 2-oxazolidone is reacted with a substituted dihalomethane compound. The resulting compound is cyclized, dehydrohalogenated and hydrolyzed to yield the desired product. These cyclopropane carboxylic acids are useful precursors for pyrethroid insecticides.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H144NO – PubChem

 

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Remote, Late-Stage Oxidation of Aliphatic C-H Bonds in Amide-Containing Molecules

Amide-containing molecules are ubiquitous in natural products, pharmaceuticals, and materials science. Due to their intermediate electron-richness, they are not amenable to any of the previously developed N-protection strategies known to enable remote aliphatic C-H oxidations. Using information gleaned from a systematic study of the main features that makes remote oxidations of amides in peptide settings possible, we developed an imidate salt protecting strategy that employs methyl trifluoromethanesulfonate as a reversible alkylating agent. The imidate salt strategy enables, for the first time, remote, nondirected, site-selective C(sp3)-H oxidation with Fe(PDP) and Fe(CF3PDP) catalysis in the presence of a broad scope of tertiary amides, anilide, 2-pyridone, and carbamate functionality. Secondary and primary amides can be masked as N-Ns amides to undergo remote oxidation. This novel imidate strategy facilitates late-stage oxidations in a broader scope of medicinally important molecules and may find use in other C-H oxidations and metal-mediated reactions that do not tolerate amide functionality.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H855NO – PubChem

 

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Stereoselective oxindole synthesis by palladium-catalyzed cyclization reaction of 2-(alkynyl)aryl isocyanates with amides

A new cyclization reaction occurred on treatment of 2-(alkynyl)aryl isocyanates with amides in the presence of a palladium(0)/diphosphine catalyst to stereoselectively form 3-(amidoalkylidene)oxindoles. A carbon-nitrogen bond as well as a carbon-carbon bond were simultaneously introduced onto the alkyne moiety to construct an oxindole skeleton with stereoselective placement of the amino substituent cis to the carbonyl group.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H822NO – PubChem

 

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Loss of the tert-butyloxycarbonyl (Boc) protecting group under basic conditions

Reaction of 3, the N-Boc, O-tosyl derivative of phenylalaninol, with base leads to loss of the Boc and tosyl groups and formation of oxazolidinone 9. Similar reactions have also been examined. A mechanism to explain loss of the Boc group under basic reaction conditions is proposed.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H460NO – PubChem

 

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Recent advances in synthesis of functionalized beta-lactams through cyclization of N-propargyl amine/amide derivatives

beta-lactams have attracted a significant attention due to their potential biological activities and wide variety of synthetic applications. Developing novel and efficient methods for construction of functionalized beta-lactams has been the subject of a number of papers in recent years. N-Propargyl amines/amides are one of the most specific class of alkynes having diverse reaction patterns. It is well known that they can undergo a number of cyclization reactions to produce various significant nitrogen containing heterocycles. This review surveys literature methods for the synthesis of highly substituted beta-lactams from simple and easily available N-propargyl amine/amide derivatives from 1991 to 2017.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H1088NO – PubChem

 

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IMIDAZOPYRAZINES AS LSD1 INHIBITORS

The present invention is directed to imidazo[1,2-a]pyrazine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H252NO – PubChem

 

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A practical and effective ruthenium trichloride-based protocol for the regio- and stereoselective catalytic hydroamidation of terminal alkynes

A rational catalyst development based on mechanistic and spectroscopic investigations led to the discovery of a new protocol for catalytic hydroamidation reactions that draws on easily available ruthenium trichloride trihydrate (RuCl3·3H2O) as the catalyst precursor instead of the previously employed, expensive bis(2-methylallyl)(1,5- cyclooctadiene) ruthenium(II). This practical and easy-to-use protocol dramatically improves the synthetic applicability of Ru-catalyzed hydroamidations. The catalyst, generated in situ from ruthenium(III) chloride hydrate, tri-n-butylphosphine, 4-(dimethylamino)-pyridine and potassium carbonate, effectively promotes the addition of secondary amides, lactams and carbamates to terminal alkynes under formation of (E)-anti-Markovnikov enamides. The scope of the new protocol is demonstrated by the synthesis of 24 functionalized enamide derivatives, among them valuable intermediates for organic synthesis.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H563NO – PubChem