DABSO as a SO2 gas surrogate in the synthesis of organic structures.

1,4-Diazabicyclo[2.2.2]octane bis(sulfur dioxide), DABCO·SO2, or DABSO, a bench-stable colorless solid, is industrially produced by the reaction of DABCO with condensed and bubbled sulfur dioxide gas at a low temperature. However, in some cases, it could catalyze organic reactions. DABSO is mostly used as a surrogate of gaseous sulfur dioxide to react with organic substrates, including Grignard reagents, aryl or alkyl halides, boronic acids, various amines, diazonium salts, carboxylic acids, heterocycles, acrylamides, alkenes, alkynes, and ß-alkynyl ketones, through one-pot protocols, annulation, or coupling reactions. Most of these synthetic reactions proceed via the formation of a sulfinate radical or anion. Using DABSO as a reagent, various simple to complex structures can be constructed, such as metal sulfinates, sulfonyl fluorides, sulfonamides, sulfonohydrazides, sulfonic esters, sulfonic thioesters, and sulfones. In this review, we want to investigate mechanistically the role of DABSO in organic synthesis.

Synthesis of Spiro-ß-lactam-pyrroloquinolines as Fused Heterocyclic Scaffolds through Post-transformation Reactions.

A sequential post-transformation of Ugi four-component reaction/nucleophilic substitution was developed for the synthesis of spiro-ß-lactam-pyrroloquinolines. This method involves the Ugi-4CR of 2-chloro-3-formyl quinolines 1a-h, amines 2a-d, 2-chloroacetic acid 3, and isocyanides 4a, 4b for the synthesis of versatile precursors 5a-v. The Ugi adducts were intramolecularly cyclized under basic conditions through the sequential nucleophilic aromatic substitution (SNAr)/second-order nucleophilic substitution (SN2) reaction to give spiro-ß-lactam-pyrroloquinoline scaffolds 6a-t. This approach is an efficient method for the synthesis of fused bioactive heterocyclic backbones containing quinoline, pyrrolidone, and ß-lactam with high bond-forming efficiency.

Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4-Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate.

A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC50 values of 1.268 and 3.254 µm, respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors.

Chemical Wastes in the Peptide Synthesis Process and Ways to Reduce Them.

In recent decades, a growing interest has been observed among pharmaceutical companies in producing and selling 80 FDA-approved therapeutic peptides. However, there are many drawbacks to peptide synthesis at the academic and industrial scales, involving the use of large amounts of highly hazardous coupling reagents and solvents. This review focuses on hideous and observant wastes produced before, during, and after peptide synthesis and proposes some solutions to reduce them.

Synthesis and Decarboxylation of Functionalized 2-Pyridone-3-carboxylic Acids and Evaluation of their Antimicrobial Activity and Molecular Docking.

The functionalized 2-pyridone-3-carboxylic acids were synthesized starting from 3-formylchromone. Meanwhile, a decarboxylation reaction of 2-pyridone-3-carboxylic acid was performed by potassium carbonate in toluene. All compounds were evaluated against two Gram-negative bacteria (Escherichia coli (E. coli), Acinetobacter baumannii (A. baumannii)) and two Gram-positive (Staphylococcus aureus (S. aureus)) and fungus (Candida albicans (C. albicans)) using serial broth dilution method. The antimicrobial screening revealed that S. aureus is the highest sensitive microorganism towards the synthesized compounds. Among all analogs, derivatives, 4p and 5c showed excellent activities in comparison with the other compounds against S. aureus. Molecular docking showed that the most active anti S. aureus are compounds 4p and 5c exhibiting primary interaction as with fluoroquinolones by cross-linking over DNA gyrase active site via metal ion bridge and H-bonding interaction with Ser84 and Glu88 from GyrA subunit along with Arg458 and Asp437 located at GyrB subunit. In addition, based on the molecular dynamic simulation as like the standard fluoroquinolones, the mentioned compounds were stabilized for significant amount of simulation time over DNA gyrase which potentiate the importance of the mentioned residues in the DNA gate region of DNA gyrase.

Synthesis of Novel Peptides Using Unusual Amino Acids.

Small peptides are valuable peptides due to their extended biological activities. Their activities could be categorized according to their low antigenicity, osmotic pressure, and also because of their astonishing bioactivities. For example, the aggression of Phe-Phe fibers via self-assembly and intermolecular hydrogen bonding is the main reason for the formation of Alzheimer's ß-amyloid fibrils. Hydrogen bonding is the main intramolecular interaction in peptides, while the presence of aromatic ring leads to the π-π stacking and affects the self-assembly and aggression. Thus, insertion of an unusual amino acid into peptide sequence facilitates the formation of intramolecular bonds, lipophilicity and its conformation. To design new small peptides with remarkable lipophilicity, it is an idea to employ γ-amino acid, such as gabapentin (H2N-Gpn-OMe) and baclofen (H2N-Baclofen-OMe), in the structure of small peptides to increase cell-penetrating properties and to prevent aggression of Phe-Phe fibrils in ß-amyloids of Alzheimer's disease. Some new tri- and tetrapeptides were synthesized through introducing biologically active gabapentin and baclofen to dipeptide of phenylalanine (Phe-Phe) through solution phase peptide synthesis strategy.

Efficient Synthesis of Norbuprenorphines Coupled with Enkephalins and Investigation of Their Permeability.

An efficient approach for the synthesis of norbuprenorphin derivatives through coupling of enkephalins and norbuprenorphine intermediates is described. Norbuprenorphine derivative was synthesized from thebaine and then, its reaction with succinic acid and phthalic acid was also studied. Meanwhile, the synthesis of enkephalins was done using solid phase peptide synthesis approach. Furthermore, after cleavage of the peptide from the surface of the resin, the coupling of enkephalins with norbuprenorphine derivative was done using TBTU as a coupling reagent then the derivatives were purified using preparative high-pressure liquid chromatography and their structures were confirmed using high-resolution mass spectrometry data. Later, their permeability across membranes was investigated. After PAMPA studies, it was found that the permeability of all norbuprenorphin-enkephalin derivatives was increased; however, succinic and phthalic acid derivatives showed higher permeability than norbuprenorphine-Leu-enkephalin.