RESUMEN
Since its introduction in 1981, the chemistry of self-immolative systems has received increasing attention in different application areas, such as analytical chemistry, medicinal chemistry, and materials science. This strategy is based on a stimulation that triggers a cascade of disassembling reactions leading to the release of smaller molecules. The particular reactivity of the nitro group, due to its powerful electron-withdrawing nature, has been exploited in the field of self-immolative chemistry. In this context, the present review describes the major role of the nitro group in self-immolative processes depending on its position.
RESUMEN
We describe herein the intermolecular addition reaction of benzyl halides to aldehydes and imines using photoactivated tetrakis(dimethylamino)ethylene (TDAE) as superphotoreductant. 3,4-Dihydroisocoumarins, 1,2-diarylethanols, and 1,2-diarylcarbamates were obtained with good functional group tolerance using simple, mild, and metal-free conditions.
RESUMEN
We report here the intermolecular metal-free addition reaction of functionalized benzyl halides to aldehydes using a super electron donor (SED). The metal-free and mild conditions allowed the formation of 3,4-dihydroisocoumarins and 1,2-diarylethanols with unprecedented functional group tolerance.
RESUMEN
Metronidazole is one of the first-line treatments for non-severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure-activity relationships previously described for the 5-nitroimidazole series have shown that functionalization at the 2- and 4-positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4-disubstituted 5-nitroimidazole compounds that show potent antibacterial activity against C.â difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4-position and a unimolecular radical nucleophilic substitution (SRN 1) reaction to introduce an ethylenic function at the 2-position of the 5-nitroimidazole scaffold.
Asunto(s)
Antibacterianos/síntesis química , Infecciones por Clostridium/tratamiento farmacológico , Nitroimidazoles/síntesis química , Animales , Antibacterianos/farmacología , Células CHO , Supervivencia Celular/efectos de los fármacos , Clostridioides difficile/efectos de los fármacos , Cricetulus , Diseño de Fármacos , Farmacorresistencia Bacteriana/efectos de los fármacos , Humanos , Metronidazol/farmacología , Estructura Molecular , Nitroimidazoles/farmacología , Relación Estructura-Actividad , Sulfonas/químicaRESUMEN
A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole derivatives with antibacterial and antiparasitic properties.
Asunto(s)
Antibacterianos , Antiparasitarios , Nitroimidazoles , Antibacterianos/síntesis química , Antibacterianos/química , Antiparasitarios/síntesis química , Antiparasitarios/química , Nitroimidazoles/síntesis química , Nitroimidazoles/químicaRESUMEN
A mild and metal-free regiodivergent addition of carbon nucleophiles to α,ß-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to α,ß-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and α,ß-unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity.
Asunto(s)
Aldehídos/química , Carbono/química , Técnicas de Química Sintética/métodos , Metales/química , Nitrobencenos/química , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Estructura Molecular , Sales (Química)/química , EstereoisomerismoRESUMEN
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.
Asunto(s)
Amidas/síntesis química , Nitroimidazoles/química , Amidas/química , Estructura Molecular , EstereoisomerismoRESUMEN
Decarboxylative cross-coupling reactions of substituted 2-carboxyazine N-oxides, with a variety of (hetero)aryl halides, by bimetallic Pd(0)/Cu(I) and Pd(0)/Ag(I) catalysis are reported. Two possible pathways, a conventional bimetallic-catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C-H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2-carboxyazine series.
RESUMEN
We report herein an original and rapid synthesis of 2,3-diaryl N-tosylaziridines by TDAE strategy starting from ortho- or para-nitro(dichloromethyl)benzene derivatives and N-tosylimines. A mixture of cis/trans isomers was isolated from 1-(dichloromethyl)-4-nitrobenzene, whereas only trans-aziridines were obtained from ortho-nitro derivatives.
Asunto(s)
Aziridinas/síntesis química , Dimetilaminas/química , Etilenos/química , Nitrobencenos/síntesis química , Aziridinas/química , Dimetilaminas/síntesis química , Etilenos/síntesis química , Nitrobencenos/química , EstereoisomerismoRESUMEN
A novel chiral N-mesyloxycarbamate to perform rhodium-catalyzed stereoselective C-H amination reactions is reported. Chiral benzylic and propargylic amines are produced in good yields and selectivities using ethyl acetate as solvent. The corresponding free amines are easily obtained by cleavage of the chiral reagent, which could also be recovered.
Asunto(s)
Aminas/química , Carbono/química , Hidrógeno/química , Acetatos/química , Aminación , Bencilaminas/química , Catálisis , Pargilina/análogos & derivados , Pargilina/química , Propilaminas/química , Rodio/química , EstereoisomerismoRESUMEN
The first stereoselective rhodium-catalyzed intermolecular aziridination and C-H amination of alkenes to produce chiral carbamate-protected aziridines and allylic amines is described. Good yields and diastereoselectivities were achieved using a readily available chiral N-tosyloxycarbamate and stoichiometric amount of the alkene substrate. Furthermore the protecting group is easy to cleave under mild reaction conditions.
Asunto(s)
Alquenos/química , Aziridinas/química , Rodio/química , Aminación , Aziridinas/síntesis química , Carbamatos/síntesis química , Carbamatos/química , Catálisis , Técnicas Químicas Combinatorias , Estructura Molecular , EstereoisomerismoRESUMEN
An efficient synthesis of enantiopure 1,3-benzothiazines has been achieved by reaction of cyclic sulfenamides and alkylpropiolate or tosylacetylene catalyzed by cesium fluoride.
RESUMEN
A new methodology, using fluoride ion as a nucleophilic catalyst, was applied for the synthesis of enantiopure 1,4-benzothiazepine from cyclic sulfenamide and electron-deficient acetylene, with high efficiency and atom economy.