One-Pot Synthesis of Novel Multisubstituted 1-Alkoxyindoles.

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2·2H2O (3.3 eq) and alcohols (R1OH, 2.0 eq) for 1-2 h at 40 °C and then, base (10 eq) and alkyl halides (R2Y, 2.0 eq) for 1-4 h at 25-50 °C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.

Immobilization of platinum nanoparticles on the functionalized chitosan particles: an efficient catalyst for reduction of nitro compounds and tandem reductive Ugi reactions.

In this work, we reported a facile synthesis of Pt nanoparticles (NPs) on proline-functionalized cross-linked chitosan particles to catalyze the reduction of R-NO2 to R-NH2 in aqueous medium using sodium borohydride. Chitosan was functionalized with (3-bromopropyl)proline and cross-linked with glutaraldehyde for the synthesis of chitosan NPs. The platinum NPs was prepared on the chitosan NPs. This catalyst showed the good selectivity and activity for reduction of nitro compound as well as for tandem reduction of nitro groups in Ugi reaction.

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation.

A backbone amide bond protecting group, 2-hydroxy-4-methoxy-5-nitrobenzyl (Hmnb), improved the synthesis of aggregation and aspartimide-prone peptides. Introduction of Hmnb is automated and carried out during peptide assembly by addition of 4-methoxy-5-nitrosalicylaldehyde to the peptidyl-resin and on-resin reduction to the secondary amine. Acylation of the hindered secondary amine is aided by the formation of an internal nitrophenol ester that undergoes a favourable O,N intramolecular acyl transfer. This activated ester participates in the coupling and generally gives complete reaction with standard coupling conditions. Hmnb is easily available in a single preparative step from commercially available material. Different methods for removing the amide protecting group were explored. The protecting group is labile to acidolysis, following reduction of the nitro group to the aniline. The two main uses of backbone protection of preventing aspartimide formation and of overcoming difficult sequences are demonstrated, first with the synthesis of a challenging aspartimide-prone test sequence and then with the classic difficult sequence ACP (65-74) and a 23-mer homopolymer of polyalanine.

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane.

The metal-free reduction of nitro compounds to amines mediated by trichlorosilane was successfully performed for the first time under continuous-flow conditions. Aromatic as well as aliphatic nitro derivatives were converted to the corresponding primary amines in high yields and very short reaction times with no need for purification. The methodology was also extended to the synthesis of two synthetically relevant intermediates (precursors of baclofen and boscalid).

Anaerobic biotransformation of fluoronitrobenzenes and microbial communities in methanogenic systems.

The fluorinated compounds are becoming a ubiquitous class of environmental contaminants because of their widespread applications, and their fate is a matter of great concern under anaerobic environment. In this work, the biotransformation of five fluoronitrobenzenes (FNBs), i.e., 2-fluoronitrobenzene (2-FNB), 3-fluoronitrobenzene (3-FNB), 4-fluoronitrobenzene (4-FNB), 2,4-difluoronitrobenzene (2,4-DFNB), and 2,3,4-trifluoronitrobenzene (2,3,4-TFNB), under methanogenic conditions had been studied by semicontinuous and batch tests for the first time. In 245 days, the five FNBs except 3-FNB were transformed mainly via nitro-reduction, and the reductive defluorination was not observed. During the biotransformation of 3-FNB, the reductive defluorination occurred after 98 days; however, its product was not aniline. The maximum transformation rates of 2-FNB, 3-FNB, 4-FNB, 2,4-DFNB, and 2,3,4-TFNB were 21.21 ± 1.73, 32.14 ± 2.33, 21.33 ± 2.48, 33.89 ± 6.87, and 10.87 ± 0.84 mg FNB (g VSS h)(-1), respectively. With the increase in the number of the fluorous groups, the transformation rates did not increase. Besides, the microbial communities were characterized by means of denaturing gradient gel electrophoresis (DGGE). Results showed that the predominant archaea were Methanobacterium, Methanosphaerula, Methanofollis, Methanospirillum, Methanolinea, and Methanosaeta; the predominant bacteria were Sphingbacteriales, Flavobacteriales, bacteroidales, Deltaproteobacteria, Desulfovibrionales, Clostridates, and Pseudomonadates. Few bacteria found were with high similarity to dechlorinating microorganisms reported. The results demonstrated that the pathways of FNBs biotransformation were different from those of the chloronitrobenzenes under methanogenic conditions.

DNA-Compatible Nitro Reduction and Synthesis of Benzimidazoles.

A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moiety attached to an encoding DNA oligomer. The library structure diversity is often limited to DNA-compatible chemical reactions in aqueous media. Herein, we describe a facile process for reducing aryl nitro groups to aryl amines by using sodium dithionite (Na2S2O4). The new protocol offers simple operation and circumvents the pyrophoric potential of the conventional method (Raney nickel). The utility of this method is demonstrated by the versatile synthesis of benzimidazoles on DNA.

Palladium Nanoparticles on a Creatine-Modified Bentonite Support: An Efficient and Sustainable Catalyst for Nitroarene Reduction.

Creatine as the nitrogen-rich, green and cheap compound is used for modification of natural bentonite and the resulting material is employed for the stabilization of Palladium nanoparticles having an average diameter of 3 nm. This new material bento-crt@Pd is characterized using different techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), solid state UV-vis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDX). This green catalyst promotes efficient reduction of aromatic nitro compounds in aqueous media. By using this catalyst nitroarenes having electron donating as well as electron withdrawing groups were reduced efficiently to their corresponding amines at room temperature. The catalyst can be recycled seven times and the reused catalyst was characterized by TEM and XPS.

Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains.

Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA.

Improvement of synthesis process of mirabegron / 中国药科大学学报

@#Overactive bladder is a syndrome characterized by urgent urination, often accompanied by frequent urination and nocturia. The incidence of the disease is high all over the world, and it has a great impact on the lives of patients, which has been paid more and more attention by scholars at home and abroad. It is currently estimated that 50 million to 100 million people worldwide suffer from the disease. Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, R-(-)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.