Dacheng Yang

A facile and efficient method for the selective deacylation of N-arylacetamides and 2-chloro-N-arylacetamides catalyzed by SOCl2

Thionyl chloride efficiently and selectively promoted the deacylation of N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions, without effecting the ester group, aminosulfonyl group, or benzyloxyamide group. This method, which has been successfully applied to a variety of substrates including different N-arylacetamides and 2-chloro-N-arylacetamides, has the attractive advantages of inexpensive reagents, satisfactory selectivity, excellent yields, short reaction time, and convenient workup. This new method can probably be used to selectively deacylate between aromatic amides and alkyl amides.

Design, synthesis, and biological evaluation of dihydroartemisinin–fluoroquinolone conjugates as a novel type of potential antitubercular agents

Tuberculosis remains a global public health problem in recent years. To develop novel type of potential antitubercular agents, twelve novel dihydroartemisinin-fluoroquinolone (DHA-FQ) conjugates (three types of molecules) were gradually designed and conveniently synthesized. All the newly synthesized conjugates were well characterized and evaluated against different Mycobacterium tuberculosis strains in vitro. The screening results showed that five DHA-FQ conjugates were active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest inhibitory activity (MIC=0.0625 μg/mL), which was comparable to the positive control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also displayed comparable activities against various clinically isolated sensitive and resistant M. tuberculosis strains (MIC=0.125-16 μg/mL) to Moxifloxacin. All target compounds possessed selective anti-M. tuberculosis ability. Preliminary structure-activity relationship demonstrated that short linker between DHA and FQ was favorable for strong antitubercular activity. This study provides a new clue for the development of novel antitubercular lead molecules.

Kinetics and mechanism of the reactions of o- and p-nitrohalobeszenes with the sodium salt of ethyl cyanoacetate carbanion: a non-chain radical nucleophilic substitution mechanism

The nucleophilic substitution reactions of o-nitroehlorobenzene (1a), o-nitrobromobenzene (lb), p-nitrofluorobenzene (1c), p-nitrochlorobenzene (1d), p-nitrobromobenzene (1e), and p-nitroiodobenzene (1f) with the sodium salt of ethyl cyanoaceaate carbanion (2) in DMSO all gave the corresponding substitution producss in almost quantitative yields. With the exception of the reaction of 1c with 2, the ESR spectra for the corresponding reactive intermediates, the radical anions of nitrophenyl halides were recorded. The relative intensity of ESR absorption versus time curves at various temperatures for the o-nitrochlorobenzene radical anion (3a), p-nitrochlorobenzene radical anion(3d), and p-nitrobromobenzene radical anion (3e) formed in the reactions of 1a, 1d, and 1e with 2 respectively in DMSO were measured by means of an ESR F/F lock technique. The kinetic curves obtained are consistent with the successive pseudo first-order reaction, and the rate constanss for the single electron transfer reactions of 1a, 1d, and 1e with 2 respectively and for the dissociation reactions of 3a, 3d, and 3e and the corresponding activaiion parameters were calculated. The results provide conclusive evidence that the thermal reactions of o- and p-nitrohalobenzeses (with the possible exception of 1c) with 2 proceed via a non-chann radical nucleophilic substitution mechanism.

Design, synthesis, and evaluation of novel l -phenylglycine derivatives as potential PPARγ lead compounds

In accordance with the structural characteristics of thiazolidinedione drugs and highly bioactive tyrosine derivatives, we tentatively designed the l-phenylglycine derivatives TM1 and TM2 based on basic principles of drug design and then synthesized them. The in vitro screening of peroxisome proliferator-activated receptor gamma (PPARγ) activated activity, α-glucosidase inhibitory and dipeptidyl peptidase-4 inhibitory activities showed that the novel molecule M5 had efficient PPAR response element (PPRE) activated activity (PPRE relative activity 105.04% at 10 μg·mL-1 compared with the positive control pioglitazone, with 100% activity). Therefore, M5 was selected as the hit compound from which the TM3 and TM4 series of compounds were further designed and synthesized. Based on the PPRE relative activities of TM3 and TM4, we discovered another new molecule, TM4h, which had the strongest PPRE relative activity (120.42% at 10 μg·mL-1). In addition, the concentration-dependent activity of the highly active compounds was determined by assaying their half-maximal effective concentration (EC50) values. The molecular physical parameter calculation and the molecular toxicity prediction were used to theoretically evaluate the lead-likeness and safety of the active compounds. In conclusion, we identified a potential PPARγ lead molecule and developed a tangible strategy for antidiabetic drug development.

Trifluoroacetic Acid–Catalyzed Synthesis of N-(1-(3-Chlorophenyl)-3-aryl-3-oxopropyl)-2-(4-nitrophenyl)acetamides via Dakin–West Reaction

Abstract A series of novel N-(1-(3-chlorophenyl)-3-aryl-3-oxopropyl)-2-(4-nitrophenyl) acetamides were synthesized using p-nitrophenylacetonitrile, m-chlorobenzaldehyde, and aryl methyl ketones as starting materials and trifluoroacetic acid (TFA) as catalyst. This realized an improved Dakin–West reaction in which p-nitrophenylacetonitrile was involved. The chemical structures of up to 15 target molecules were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry. This method provides a facile synthetic protocol under more moderate reaction conditions, smaller dosage (0.40 mol%) and hence lower cost of catalyst, and simpler posttreatment in comparison to other known methods. A reaction mechanism is proposed in which hydroxyacetophenone is first catalytically converted into the corresponding acetoxyacetophenone prior to be involved in the subsequent Dakin–West reaction that eventually leads to hydroxyl-acetylated target compounds. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT