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A novel ring-opening reaction of donor–acceptor cyclopropanes (DACs) through a one-pot three-component nucleophilic addition of amines, CS2, and DACs has been described. New γ-dithiocarbamate dialkyl malonate skeletons were obtained in up to 97% yield.

Using DABSO as a substrate, different simple to complex structures can be constructed, such as sulfonyl fluorides, sulfonamides, sulfonohydrazides, sulfonic esters, and sulfones. In this review, we investigate the role of DABSO in organic synthesis.

We describe a novel, simple, robust, and efficient cyclization/deoxygenation approach for the synthesis of functionalized isoquinoline derivatives. Over the course of continued studies on o-alkynylbenzaldoxime cyclization reactions, the formation of cyclic nitrones through 6-endo-dig cyclization was achieved using silver triflate or bromine as an electrophile, and subsequently, the deoxygenation process was carried out in the presence of CS2 in good to high yields.

An efficient strategy for the synthesis of functionalized 1-aminoisoquinoline derivatives has been developed through the reaction of o-alkynylbenzaldoximes with 2H-azirines using electrophiles.

A diastereoselective cascade annulation between allenoates and

Kisspeptin (kp) is a key regulator of reproduction, which stimulates sexual maturation and gametogenesis in mammals, amphibians, and teleosts. In the present study, to enhance the biological activity of kp10, a novel analog (referred to as M-kp10) was designed based on the endogenous goldfish variant, in which phenylalanine 6 was substituted by tryptophan and the N-terminus was acetylated. Compared with the native kp-10 and salmon gonadotropin-releasing hormone (GnRH3), the effect of M-kp10 on sexual hormones and reproductive indices as well as the expression of kiss1, cyp19a1, and kiss1ra genes in goldfish (Carassius auratus) was investigated. In practice, peptides were synthesized based on the standard Fmoc-solid-phase peptide synthesis and purified by employing RP-HPLC, followed by approving their structure using ESI-MS. The results showed that M-kp10 increased significantly 17,20β-DHP, LH, FSH and E2 as well as fecundity, hatching and fertilization percentages than the other peptides. Histological studies revealed that M-kp10 led to the faster growth of ovarian follicles compared to the kp-10 and GnRH3. The genes of cyp19a1, kiss1ra, and kiss1 were remarkably more expressed after treatment with M-kp10. In conclusion, the results indicated the superiority of M-kp10 over kp-10 in inducing sexual maturation and accelerating the percentage of fecundity, suggesting that M-kp10 could be a promising candidate for application in the artificial breeding of fish.

This manuscript reports an impressive and facile strategy for synthesizing isoxazole derivatives using immobilized Cu (I) in metformin-functionalized β-cyclodextrin as a catalyst. The architecture of this catalyst was characterized by different analytical techniques such as Fourier transform infrared spectroscopy, Thermogravimetric analysis, X-ray diffraction, Field emission scanning electron microscopy, and Energy-dispersive X-ray spectroscopy. The catalyst showed remarkable reusability even after 7 consecutive runs.

A transition-metal-free postmodification of the Groebke-Blackburn-Bienayme (GBB) reaction for the synthesis of spiro[chromene-imidazo[1,2-a]pyridin]-3'-imine was discovered. The unusual transformation represents the first example of activation and the reaction of the imidazole carbon atom. In this postcondensational modification, KOt-Bu acts as a base, which, after the isomerization of an alkyne moiety to allene, causes the next unique nucleophilic reaction of the imidazole carbon atom that results in spirocyclic structures. The proposed reaction mechanism was confirmed based on the DFT calculations.

Practical Pd-catalyzed 2-pyridones were designed to achieve chromeno[2,3-b]pyridine-2-ones. The reaction proceeds through domino nucleophilic addition and decarboxylative arylation, respectively. This methodology offers a moderately efficient approach to construct the bioactive, fused-heterocyclic skeletons via selective C-O bond formation and decarboxylative arylation in a single step with high selectivity and good yields.

We describe a novel and efficient synthetic strategy to construct the linear homoallylic quinolone structures through the intermolecular addition of 2-alkynylquinoline toiN/i-allenyl sulfonamides. We developed the regio- and diastereoselective transition metal-free hydroalkylation of 1,2-dienes by a structure containing a push-pull system. Moreover, the present work was carried out with a high atom economy, mild reaction conditions, and moderate to high yields.

Background: Proteolysis-targeting chimera (PROTAC) is a bifunctional molecule comprising a ligand to recognize the targeted protein to be degraded. Objectives: To use the advantages of the PROTAC technique, we have synthesized novel compounds to degrade inosine monophosphate dehydrogenase (IMPDH) by the proteasome system. Methods: We describe the synthesis of new PROTACs based on a combination of mycophenolic acid (MPA) as the potent IMPDH inhibitor and pomalidomide as a ligand of E3 ubiquitin ligase via linkers formed from Cu(I)-catalyzed cycloaddition reaction. Results: All synthesized compounds were investigated against Jurkat cells as acute T-cell leukemia and were potent apoptosis inducers at 50 nM. Conclusion: The effect of compound 2 in 0.05 μM on IMPDH degradation can be almost prevented by competition with bortezomib as the proteasome inhibitor at 0.1 and 0.5 μM.

A regio- and diastereoselective ring-expansion reaction of N-acylaziridines is described for the synthesis of 4-carboxamide oxazolines using InCl3. A domino Ugi–Joullié/ring-expansion reaction of arylphenylazirines, isocyanides, and carboxylic acids leads to the target products through the N-acylaziridine intermediates in the presence of the indium catalyst. The oxazolines were synthesized in moderate to excellent yields with high atom economy and high bond-forming efficiency under mild reaction conditions.

Peptide chemistry is a multidisciplinary subject, and we have recently found so many progresses in different fields in peptide chemistry. Statistical results display that the peptide researches are distributed throughout the fields of biochemistry, medicine, chemistry, immunology, and some other fields of science. According to the situation of peptides in worldwide drug marketing and increasing country’s need for manufacture of high-scaled peptide products, scientists try to find new peptide-based pharmaceuticals. In this review, we would like to summarize some of these researches including synthesis and application of peptides directed in Peptide Chemistry Research Institute of K. N. Toosi University of Technology.

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.

We employed density functional theory (DFT) methods to investigate the most plausible mechanism of cyclization/ring expansion of proline with

A straightforward route to a large and diverse library of trisubstituted imidazoles was established via a three-component reaction of 2-oxoaldehydes, 1,3-dicarbonyl compounds, and acyclic nitrogen bis-nucleophiles. The obtained products were subsequently explored in a photochemical cyclization yielding a variety of imidazole-fused polycyclic compounds.

The synthesis of pyrrolidin-5-one-2-carboxamides

In this project, a moderately efficient approach to multisubstituted N-(isoquinolin-1-yl)sulfonamide derivatives was illustrated, utilizing ortho-alkynylbenzaldoximes and zwitterionic ketenimine salts in a tandem reaction catalyzed by silver oxide. The oxophilicity of Ag2O, along with its nature as Lewis acid, pave the way for a smooth [3 + 2] cycloaddition between isoquinoline N-oxides and ketenimine species, which is a key step in this reaction. DFT calculation suggests that 1,3-dipolar cycloaddition of nitrone and ketenimine proceeds through a selective stepwise mechanism.

A novel copper-catalyzed cycloisomerization of unactivated allene-tethered O-propargyl oximes has been developed for the synthesis of hexahydropyrrolo[3,4-b]azepin-5(4H)-ones. This one-pot domino reaction proceeds via a [2,3]-sigmatropic rearrangement, a [3 + 2] cycloaddition, and another [3,3]-sigmatropic rearrangement. The methodology offers a practical and straightforward route for the rapid assembly of both ring components of the fused bicyclic motifs from acyclic precursors by simultaneously forming four new bonds (a C═O, a C═N, and two C-C bonds) in a single step.

Despite several studies on fish hormone therapy, finding new candidates may provide more reproductive efficiency in artificial propagation. Kisspeptins, being upstream of the hypothalamic-pituitary-gonadal axis, appear to play a key role in the reproduction process. In the present study, the effect of different variants of kisspeptide, including goldfish (Carassius auratus) kiss1 kisspeptin (Kiss1), human kisspeptin (Hkiss), and their combination (Kiss1 + H), on the reproductive indices of goldfish broodstock in comparison to Ovaprim (a typical synthetic Gnrh hormone) was investigated. Peptides (Kiss1 and Hkiss) were synthesized using a solid-phase synthesis approach. Kiss1 and Hkiss were injected at a dose of 100 μg kg-1 body weight, blood samples were taken 6 h after injection and sex hormones (E2, Dhp, and 11-Kt), gonadotropins (Lh and Fsh), cortisol and reproductive indices (fecundity, fertilization and hatching percentage) were measured. The results showed a significant increase of plasma sex hormones and gonadotropins in fish treated with kisspeptins. In addition, the cortisol and lipoprotein lipase in Kiss1, Hkiss and Kiss1 + H were remarkably increased compared to Ovaprim. In conclusion, kisspeptins could be a more suitable candidate than Ovaprim for accelerating and synchronizing oocyte maturation in the fisheries industry.

We have developed a new three-component approach using

Cancer is a major health concern in human populations worldwide, and due to its causes being multi-factorial, it is not easily curable. Many attempts have been made to tackle this disease in hopes of finding effective anticancer agents which are not harmful to healthy tissues. Peptides with several medicinal activities have been shown to be good candidates as anticancer agents to replace common classic anticancer drugs. Peptides in conjugation with either biologically active heterocyclic compounds or anticancer drugs may result in new molecules compiling the biological benefits of both individual compounds within a unit structure.In this study some triazole-peptide conjugates as well as ciprofloxacin-peptide conjugates were designed, synthesized, and their anticancer activities evaluated. A normal skin cell line, NIH3, was also employed to determine the safety profiles of these conjugates.Two peptides; YIGSR and LSGNK were synthesized by the solid phase peptide synthesis (SPPS) method using Wang resin. Cell viability was examined by employing the MTT assay. To determine the cytotoxicity of the triazole and ciprofloxacin conjugates, two human cancer cell lines were employed; HepG2 (human liver cancer cell line) and LNCaP (human prostatic carcinoma cell line). A human skin fibroblast cell line was also included for comparison.MTT results showed that all the compounds could inhibit the viability of cancerous cells in a concentration- dependent manner.The results showed that these peptide conjugates are toxic against the aforementioned cancerous cells and thus may raise a hope for finding new anticancer agents made by such strategy in the near future.

1,4-Diazabicyclo[2.2.2]octane bis(sulfur dioxide), DABCO·SO

A sequential post-transformation of Ugi four-component reaction/nucleophilic substitution was developed for the synthesis of spiro-β-lactam-pyrroloquinolines. This method involves the Ugi-4CR of 2-chloro-3-formyl quinolines

An efficient synthesis of diketopiperazinoindolines through an indium-catalyzed intramolecular 5-exo-dig cyclization of ortho-alkynyl diketopiperazines has been reported. The formation of diketopip...

Introduction Currently, gastroesophageal reflux disease (GERD) is one of the most ubiquitous problems in clinical practice. An antacid-alginate combination (under the trade name Gaviscon) is a natural-based product that effectively suppresses GERD. This product acts via the formation of viscous gel that floats on the top of the gastric content. On the other hand, efficient management of Helicobacter pylori infection with minimal side effects is an important goal for gastroenterologists. Furthermore, some H. pylori-positive patients suffer from GERD. Methods Here, we present the results of investigations on alginate conjugated to sugar codes in order to find initial clues regarding the potential ability of this conjugate in the simultaneous prophylaxis of GERD and H. pylori infection in an in vitro assay. Results It is noteworthy that our results reveal that sugar codes conjugated alginate considerably decrease (approximately 74%) the adhesion of H. pylori to gastric epithelial cells in vitro. Moreover, surprisingly after conjugation of sugar codes, alginate can maintain its ability to create gel. Our results demonstrate that alginate conjugated to sugar codes is not cytotoxic. Conclusion The preparation of these conjugates can be regarded as the first step to establish a new roadmap for the simultaneous prevention of GERD and H. pylori infection in future studies on in vivo models.

As one of the most important building blocks in organic synthesis, isocyanides come in for a wide range of transformations owing mostly to their unusual terminal carbon center adsorbed electrophiles, reacted with nucleophiles, get involved in radical reactions and coordinated with metal centers. The distinctive feature of isocyanide is its ready willingness to participate in multicomponent reactions (MCRs). MCRs represent a great tool in organic synthesis for the construction of new lead structures in a single procedure introducing both structural diversity and molecular complexity in only one step. Isocyanide-based multicomponent reactions (IMCRs) have become a powerful approach for the synthesis of complex molecules providing high degree of atom and bond economy under very mild reaction conditions. The use of enantiomerically pure isocyanides can, in principle, bring about two advantages: (i) the possibility to obtain a stereochemically diverse adduct, controlling the absolute configuration of the starting isocyanide; and (ii) the possibility to induce diastereoselection in the multicomponent reaction. The most commonly-used IMCRs are the Ugi and Passerini reactions. Many published reviews have focused on the Ugi and Passerini reactions from different viewpoints, but this review describes advances in the application of chiral isocyanides in MCRs. The rationale for applying such diversity generating chemistries is also discussed.

This minireview focuses on the recent advances in green synthesis of chromone derivatives which have been published over the last 5–10 years.

An efficient and diversity-oriented access to functionalized pyrrolidin-2-ones through an Ugi reaction of readily available starting materials with a subsequent transformation is described. A two-step reaction sequence of a four-component Ugi reaction and an intramolecular radical-cyclization reaction leads to the chemo- and regioselective formation of a single product with high atom economy and good to high yields. The radicalization of the pseudopeptides generated from the first step by a cavitational mechanism produces the key intermediate for the ultrasound-activated formation of γ-lactams as the final products by β-Michael addition. Among the advantages of this approach are its use of cavitation bubble implosion as an exclusive path to radicalization of the polyfunctional Ugi adduct, its high selectivity, and its short reaction times.

This paper describes a diversity-oriented approach to the formation of 3-oxoisoindoline-1-carboxamide derivatives utilizing the potential of the nitro group as a directing group. The reaction proceeds through a novel class of post-transformation reactions through a sequential four-component Ugi reaction/oxidative nucleophilic substitution of hydrogen. The 3-oxoisoindoline-1-carboxamide derivatives were synthesized in the presence of a base under mild reaction conditions with high regio- and chemoselectivity. The aerobic oxidation, high bond-forming efficiency, high atom economy, and good to excellent yields are the main advantages of this approach.

β-secretase 1 (BACE1) plays a pivotal role in the pathology of Alzheimer׳s disease via accumulation beta amyloid in the brain. In this context, identifying new scaffolds that block BACE1 is of great importance despite all pharmacokinetic drawbacks that peptide-like structures have. Here, we report a new core structure based on novel unusual amino acids by substituting phenyl amide group in the P1 position and small alkyl groups in the P1′ site that results in the formation of new biological active peptides in micromolar level. Three different scaffolds were designed based on docking studies to efficiently interact with critical Asp32 residue in the active site of BACE1 and incorporated in peptides synthesis by Fmoc solid-phase peptide synthesis (SPPS) methodology to achieve desired compounds in good yield. The inhibitory activity of all synthesized peptides was examined by FRET-based enzymatic assay. The peptide 7 showed the best inhibitory activity with IC50 = 98.14 µM. Results of this investigation revealed that utilizing unusual amino acids as building blocks for the synthesis of peptidomimetics would be an option for the development and optimization of pharmaceutical structures. The inhibition of β-secretase 1 (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). Novel series of peptides coupled to the new unusual amino acids scaffold were investigated as BACE1 inhibitors in this study. The design of these peptides was mostly affected by OM00-3. Based on observations, in good agreement between BACE-1 inhibition assessment and docking methodology, peptide 7 was the most potent compound between all and could be the basis of future studies.

An efficient approach for the synthesis of immobilized copper (triazole-5-yl)methanamine complexes onto MCM-41 (Cu@TZMA@MCM-41), as a novel recyclable nanocatalyst, is described. This nanocatalyst was used for the synthesis of pyridine-containing pseudopeptides through a sequential Ugi/nucleophilic addition/1,5-enyne cyclization reaction and elicited good-to-excellent yields. The nanocatalyst was fully characterized by SEM, EDS, TEM, BET, ICP-OES, TGA, and XRD techniques. Furthermore, the catalyst was recovered by simple filtration and could be used for at least 5 cycles without significant loss of activity.

An unprecedented cylcoisomerization of 1,3-dien-5-ynes for the construction of 7H-benzo[7]annulenes through a transamidation/5-exo-trig cyclization/8π-electrocyclization has been reported. Mechanistic investigations were conducted via DFT calculation and experimentally support.

A tandem reaction of 2-alkynylbenzaldoximes with propargylic alcohols has been developed for the synthesis of α-(4-bromo-isoquinolin-1-yl)-propenones. Employing 2-alkynylbenzaldoximes as a precursor in the presence of Br

Ruthenium complexes are remarkable catalysts for the C–H activation approaches and organic transformations. Combining a Ru-catalyst with oxidants and other additives in a one-pot process is considered a sustainable approach due to the reduction in reaction steps and the minimal usage of solvents during synthesis, work-up, isolation of chemicals, and purification of the products. This review highlights the ruthenium-catalyzed organic transformations in a one-pot manner to achieve heterocyclic backbones, including indoles, benzofurans, indazoles, pyrans, pyrimidines, quinolines, and isoquinolines.

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.

A transition-metal-free postmodification of the Groebke-Blackburn-Bienaymé (GBB) reaction for the synthesis of spiro[chromene-imidazo[1,2

Practical Pd-catalyzed 2-pyridones were designed to achieve chromeno[2,3