Synthetic Routes for 1,4-disubstituted 1,2,3-triazoles: A Review

2019 ◽  
Vol 23 (8) ◽  
pp. 860-900 ◽  
Author(s):  
Chander P. Kaushik ◽  
Jyoti Sangwan ◽  
Raj Luxmi ◽  
Krishan Kumar ◽  
Ashima Pahwa
Keyword(s):  
Solid Phase ◽  
Click Reaction ◽  
Biological Activities ◽  
Triazole Ring ◽  
Copper Catalysts ◽  
Biologically Active ◽  
Pharmaceutical Chemistry ◽  
Biological Targets ◽  
Synthetic Routes ◽  
High Yields

N-Heterocyclic compounds like 1,2,3-triazoles serve as a key scaffolds among organic compounds having diverse applications in the field of drug discovery, bioconjugation, material science, liquid crystals, pharmaceutical chemistry and solid phase organic synthesis. Various drugs containing 1,2,3-triazole ring which are commonly available in market includes Rufinamide, Cefatrizine, Tazobactam etc., Stability to acidic/basic hydrolysis along with significant dipole moment support triazole moiety for appreciable participation in hydrogen bonding and dipole-dipole interactions with biological targets. Huisgen 1,3-dipolar azide-alkyne cycloaddition culminate into a mixture of 1,4 and 1,5- disubstituted 1,2,3-triazoles. In 2001, Sharpless and Meldal came across with a copper(I) catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles by cycloaddition between azides and terminal alkynes. This azide-alkyne cycloaddition has been labelled as a one of the important key click reaction. Click synthesis describes chemical reactions that are simple to perform, gives high selectivity, wide in scope, fast reaction rate and high yields. Click reactions are not single specific reaction, but serve as a pathway for construction of simple to complex molecules from a variety of starting materials. In the last few decades, 1,2,3-triazoles attracted attention of researchers all over the world because of their broad spectrum of biological activities. Keeping in view the biological importance of 1,2,3-triazole, in this review we focus on the various synthetic routes for the syntheisis of 1,4-disubstituted 1,2,3-triazoles. This review involves various synthetic protocols which involves copper and non-copper catalysts, different solvents as well as substrates. It will boost synthetic chemists to explore new pathway for the development of newer biologically active 1,2,3-triazoles.

Recent Developments on Synthesis of Indole Derivatives Through Green Approaches and Their Pharmaceutical Applications

2020 ◽  
Vol 24 (22) ◽  
pp. 2665-2693
Author(s):  
Dipayan Mondal ◽  
Pankaj Lal Kalar ◽  
Shivam Kori ◽  
Shovanlal Gayen ◽  
Kalpataru Das
Keyword(s):  
Biological Activities ◽  
Synthetic Methods ◽  
Pharmaceutical Chemistry ◽  
Indole Derivatives ◽  
Biological Studies ◽  
Recent Developments ◽  
Pharmaceutical Industries ◽  
Green Methodology ◽  
Conventional Methods ◽  
High Yields

Indole moiety is often found in different classes of pharmaceutically active molecules having various biological activities including anticancer, anti-viral, anti-psychotic, antihypertensive, anti-migraine, anti-arthritis and analgesic activities. Due to enormous applications of indole derivatives in pharmaceutical chemistry, a number of conventional synthetic methods as well as green methodology have been developed for their synthesis. Green methodology has many advantages including high yields, short reaction time, and inexpensive reagents, highly efficient and environmentally benign over conventional methods. Currently, the researchers in academia as well as in pharmaceutical industries have been developing various methods for the chemical synthesis of indole based compounds via green approaches to overcome the drawbacks of conventional methods. This review reflects the last ten years developments of the various greener methods for the synthesis of indole derivatives by using microwave, ionic liquids, water, ultrasound, nanocatalyst, green catalyst, multicomponent reaction and solvent-free reactions etc. (please see the scheme below). Furthermore, the applications of green chemistry towards developments of indole containing pharmaceuticals and their biological studies have been represented in this review.

The Molecular Diversity Scope of Urazole in the Synthesis of Organic Compounds

2019 ◽  
Vol 16 (7) ◽  
pp. 953-967 ◽  
Author(s):  
Ghodsi M. Ziarani ◽  
Fatemeh Mohajer ◽  
Razieh Moradi ◽  
Parisa Mofatehnia
Keyword(s):  
Biological Activities ◽  
Biological Properties ◽  
Biologically Active ◽  
Microtubule Assembly ◽  
Heterocyclic Molecules ◽  
Biological Perspective ◽  
Highly Active ◽  
Anti Inflammatory ◽  
High Yields ◽  
Short Time

Background: As a matter of fact, nitrogen as a hetero atom among other atoms has had an important role in active biological compounds. Since heterocyclic molecules with nitrogen are highly demanded due to biological properties, 4-phenylurazole as a compound containing nitrogen might be important in the multicomponent reaction used in agrochemicals, and pharmaceuticals. Considering the case of fused derivatives “pyrazolourazoles” which are highly applicable because of their application for analgesic, antibacterial, anti-inflammatory and antidiabetic activities as HSP-72 induction inhibitors (I and III) and novel microtubule assembly inhibitors. It should be mentioned that spiro-pyrazole also has biological activities like cytotoxic, antimicrobial, anticonvulsant, antifungal, anticancer, anti-inflammatory, and cardiotonic activities. Objective: Urazole has been used in many heterocyclic compounds which are valuable in organic syntheses. This review disclosed the advances in the use of urazole as the starting material in the synthesis of various biologically active molecules from 2006 to 2019. Conclusion: Compounds of urazole (1,2,4-triazolidine-3,5-dione) are the most important molecules which are highly active from the biological perspective in the pharmaceuticals as well as polymers. In summary, many protocols for preparations of the urazole derivatives from various substrates in multi-component reactions have been reported from different aromatic and aliphatic groups which have had carbonyl groups in their structures. It is noted that several catalysts have been synthesized to afford applicable molecules with urazole scaffolds. In some papers, being environmentally friendly, short time reactions and high yields are highlighted in the protocols. There is a room to synthesize new catalysts and perform new reactions by manipulating urazole to produce biologically active compounds, even producing chiral urazole component as many groups of chiral urazole compounds are important from biological perspective.

scholarly journals THE MAIN CONCEPTS OF SYNTHESIS OF PEPTIDES AS A NEW GENERATION OF BIOLOGICALLY ACTIVE DRUGS

2021 ◽  
Vol 58 ◽  
pp. 62-65
Author(s):  
Mikhail A. Polianskii ◽  
◽  
Anatoly I. Ginak ◽  
Keyword(s):  
Large Scale ◽  
Solid Phase ◽  
Biologically Active ◽  
Solid Polymer ◽  
Environmental Standards ◽  
Polymer Carrier ◽  
Phase Synthesis ◽  
Biological Targets ◽  
Living Organisms ◽  
New Generation

Currently, peptide-based drugs are increasingly replacing dosage forms which have been widely used for many years due to their affinity for living organisms and greater selectivity to biological targets, which lead to a growing demand. To meet that demand, a method using a solid polymer carrier (solid-phase synthesis), which has no alternative for fast and large-scale synthesis, is used. Nevertheless, work on its improvement is carried out non-stop, not only to optimize the chemical process, but also to bring the process to compliance with environmental standards dictated by modern concepts of green chemistry

scholarly journals Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9.

2007 ◽  
Vol 54 (4) ◽  
pp. 805-811 ◽  
Author(s):  
Michał Manturewicz ◽  
Zbigniew Grzonka ◽  
Lenka Borovicková ◽  
Jirina Slaninová
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Activities ◽  
Synthesis Method ◽  
Oxytocin Receptor ◽  
Amide Group ◽  
Biologically Active ◽  
Side Chain ◽  
Electronic Effects

Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln(4) with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn(5) by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn(5) and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

scholarly journals A New Method for the Synthesis of 2-Substituted Benzoxazoles from 2-Nitrophenol Derivatives and Aldehydes  

2021 ◽  
Vol 31 (3) ◽  
pp. 43-46
Keyword(s):  
Biological Activities ◽  
Catalyst System ◽  
Biologically Active ◽  
New Method ◽  
Redox Catalyst ◽  
High Pressure High Temperature ◽  
One Step ◽  
High Yields ◽  
Strong Acids ◽  
Single Reaction

Benzoxazole derivatives are one of the compounds with many interesting biological activities. Conventional methods are often performed under complex conditions using strong acids, expensive metal catalysts, requiring high pressure, high temperature, and under microwave irradiation. In this study, we reported a new method of benzoxazole synthesis with redox catalyst using FeCl3.6H2O and sulfur. This is a suitable, efficient, readily available and environmentally friendly catalyst system for redox and condensation reactions in one step at 100 oC. Applying this new method, we have synthesized eight 2-arylbenzoxazole derivatives with high yields (calculated according to 2-nitrophenol). This research is an important step forward in the synthesis of biologically active compounds containing the benzoxazole framework from readily available starting materials in a single reaction.

Activated Carbon/MoO3: Efficient Catalyst for Green Synthesis of Chromeno[d]pyrimidinediones and Xanthenones

2020 ◽  
Vol 23 ◽  
Author(s):  
Niloofar Sabet Mehr ◽  
Shahrzad Abdolmohammadi ◽  
Maryam Afsharpour
Keyword(s):  
Activated Carbon ◽  
Room Temperature ◽  
Bulk Material ◽  
Biological Activities ◽  
Reaction Times ◽  
Aromatic Aldehydes ◽  
Biologically Active ◽  
Efficient Catalyst ◽  
Calcium Blockers ◽  
High Yields

Background: Nanoscale metal oxide catalysts have been extensively employed in organic reactions because they have been found to influence the chemical and physical properties of the bulk material. The chromene (benzopyran) nucleus constitutes the core structure in a major class of many biologically active compounds, and interest in their chemistry consequently continues because of their numerous biological activities. The xanthene (dibenzopyran) derivatives are classified as highly significant compounds which display a number of various bioactive properties. Pyrimidinones have also gained interest due to their remarkable biological utilization such as antiviral, antibacterial, antihypertensive, antitumor and calcium blockers effects. Objective: Our aim in the work presented herein was to prepare activated carbon/MoO3 nanocomposite and explore its role as a green and recyclable catalyst for the synthesis of chromeno[d]pyrimidinediones and xanthenones under ethanol-drop grinding at room temperature. Methods: The activated carbon/MoO3 nanocomposite was prepared successfully via a simple route in which carbonization of gums as new natural precursors was used for the synthesis of activated carbon. This nanocomposite was then effectively used in a reaction of 3,4- methylenedioxyphenol, aromatic aldehydes and active methylene compounds including 1,3-dimethylbarbituric acid and dimedone to synthesize a series of chromeno[d]pyrimidinediones and xanthenones in high yields. The synthesized catalyst was characterized by Fourier transform infrared spectroscopy (FT-IR), Powder x-ray diffractometry (XRD), Scanning electron microscope (SEM), Raman spectroscopy, and also by TGA analysis. Confirmation of the structures of compounds 5(a-g) and 6(a-g) were also established with IR, 1 H NMR and 13C NMR spectroscopic data and also by elemental analyses. Results: A number of 6,8-dimethyl-10-phenyl-6,10-dihydro-7H-[1,3]dioxolo[4΄,5΄:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-diones and 7,7- dimethyl-10-(4-methylphenyl)-6,7,8,10-tetrahydro-9H-[1,3]dioxolo[4,5-b]xanthen-9-ones were effectively synthesized using activated carbon/MoO3 nanocomposite (0.05 gr) as catalyst under ethanol-drop grinding at room temperature. The desired products were obtained in high yields (93-97%) within short reaction times (15-20 min). Conclusion: This paper investigates the catalytic potential of the synthesized activated carbon/MoO3 nanocomposite for the prepataion of chromeno[d]pyrimidinediones and xanthenones under ethanol-drop grinding procedure. The mildness of the reaction conditions, high yields of products, short reaction times, experimental simplicity, and avoid the use of harmful solvents or reagents makes this procedure preferable for the synthesis of these compounds.

Computational studies of biologically active alkaloids of plant origin: an overview

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Mireille K. Bilonda ◽  
Liliana Mammino
Keyword(s):  
Drug Development ◽  
Biological Activities ◽  
Docking Studies ◽  
Biologically Active ◽  
The Other ◽  
Computational Studies ◽  
Biological Targets ◽  
Theoretical Approaches ◽  
Structure Activity ◽  
Source Of Information

AbstractComputational studies nowadays constitute a crucial source of information for drug development, because they provide information on many molecular properties and also enable predictions of the properties of not-yet-synthesized compounds. Alkaloids are a vast group of natural products exhibiting a variety of biological activities, many of which are interesting for drug development. On the other hand, computational studies of biologically active alkaloids have so far mostly focused on few particularly relevant or “popular” molecules, such as quinine, caffeine, or cocaine, with only few works on the other molecules. The present work offers an overview of existing computational studies on alkaloid molecules, from the earliest ones to the most recent, and considering all the theoretical approaches with which studies have been performed (both quantum mechanics and molecular dynamics). The considered studies are grouped according to their objectives and outcomes, such as conformational analysis of alkaloid molecules, effects of selected solvents on their properties, docking studies aimed at better understanding of the interactions between alkaloid molecules and biological targets, studies focusing on structure activity relationships, and computational studies performed to confirm experimental results. It is concluded that it would be important that computational studies on many other alkaloid molecules are performed and their results made available, covering their different classes as well as the variety of their biological activities, to attain better understanding of the properties not only of individual molecules, but also of groups of related molecules and of the overall alkaloids family.

scholarly journals Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 682
Author(s):  
Ana Rita Neves ◽  
Daniela Pereira ◽  
Catarina Gonçalves ◽  
Joana Cardoso ◽  
Eugénia Pinto ◽  
...  
Keyword(s):  
Click Reaction ◽  
Biological Activities ◽  
Triazole Ring ◽  
Artemia Salina ◽  
Significant Inhibition ◽  
Bacterial Biofilm ◽  
Marine Microorganisms ◽  
Negative Effects ◽  
Biofilm Growth ◽  
Bacteria And Fungi

Marine biofouling is a natural process that represents major economic, environmental, and health concerns. Some booster biocides have been used in biofouling control, however, they were found to accumulate in environmental compartments, showing negative effects on marine organisms. Therefore, it is urgent to develop new eco-friendly alternatives. Phenyl ketones, such as benzophenones and acetophenones, have been described as modulators of several biological activities, including antifouling activity (AF). In this work, acetophenones were combined with other chemical substrates through a 1,2,3-triazole ring, a strategy commonly used in Medicinal Chemistry. In our approach, a library of 14 new acetophenone–triazole hybrids was obtained through the copper(I)-catalyzed alkyne-azide cycloaddition “click” reaction. All of the synthesized compounds were evaluated against the settlement of a representative macrofouling species, Mytilus galloprovincialis, as well as on biofilm-forming marine microorganisms, including bacteria and fungi. The growth of the microalgae Navicula sp. was also evaluated after exposure to the most promising compounds. While compounds 6a, 7a, and 9a caused significant inhibition of the settlement of mussel larvae, compounds 3b, 4b, and 7b were able to inhibit Roseobacter litoralis bacterial biofilm growth. Interestingly, acetophenone 7a displayed activity against both mussel larvae and the microalgae Navicula sp., suggesting a complementary action of this compound against macro- and microfouling species. The most potent compounds (6a, 7a, and 9a) also showed to be less toxic to the non-target species Artemia salina than the biocide Econea®. Regarding both AF potency and ecotoxicity activity evaluation, acetophenones 7a and 9a were put forward in this work as promising eco-friendly AF agents.

scholarly journals Triterpenoids and Phytosterols Isolated from Pluchea Indica L. Leaves

2019 ◽  
Vol 35 (2) ◽  
Author(s):  
Do Thi Viet Huong ◽  
Phan Minh Giang ◽  
Hoang Thi Sim ◽  
Truong Thi To Chinh
Keyword(s):  
Glucose Transporter ◽  
Biological Activities ◽  
Biologically Active ◽  
Viet Nam ◽  
Onopordum Acanthium ◽  
Nutrition Research ◽  
Glycerol Ester ◽  
Nmr Techniques ◽  
High Yields ◽  
Rats And Mice

Abstract: Taraxasterol acetate, 1-dotriacontanol, taraxasterol, stigmasterol, 2-(prop-1-ynyl)-5-(5,6-dihyroxyhexa-1,3-diynyl)thiophene), stigmasterol 3-O-β-D-glucopyranoside, and β-sitosterol 3-O-β-D-glucopyranoside were isolated from the leaves of Pluchea indica and determined with NMR techniques. Taraxasterol acetate, taraxasterol, and stigmasterol could be isolated in high yields from Pluchea indica growing in Gia Lam, Hanoi, Vietnam.  Keywords: Pluchea indica, phytosterol, triterpenoid, taraxasterol, stigmasterol. References: [1] Đỗ Tất Lợi, Những cây thuốc và vị thuốc Việt Nam, NXB Hồng Đức, Thanh Hóa. (2014) 562 & 604. [2] H. Hussain, A. Al-Harrasi, G. Abba, N.U. Rheman, F. Mabood, I. Ahmed, M. Saleem, T. Van Ree, I.R. Green, S. Anwar, A. Badshah, A. Shah, I. Ali. The genus Pluchea: Phytochemistry, Traditional uses, and Biological activities. Chemistry & Biodiversity. 10(2011), 1944-1969.[3] Đoàn Thanh Tường, Phạm Hoàng Ngọc, Đỗ Đình Rãng. Nghiên cứu về một số cấu tử chính của tinh dầu Cúc tần. Thông báo khoa học Trường Đại học Sư phạm - Đại học Quốc gia Hà Nội. 4 (199) (2015), 45-50.[4] Vũ Việt Nam, Trần Ngọc Ninh, Mc Leod J., Nguyễn Xuân Dũng. Kết quả nghiên cứu một số cây thuộc họ Cúc. Tạp chí Dược liệu. 4 (2) (1999), 44-47. [5] Phan Minh Giang, Đỗ Thị Việt Hương, Nguyễn Ngọc Diệp, Nguyễn Mạnh Quyết. Một số hợp chất terpenoid và acid phenolic từ cây mẫn tưới. Tạp chí Dược liệu. 23 (4) (2018), 195-199.[6] L.M. Khalilov, A. Z. Khalilova A, E. R. Shakurova, I.F. Nuriev, A. S. Kachala, A.S. Shashkov, U.M. Dzhemilev. PMR and 13C NMR spectra of biologically active compunds. XII. Taraxasterol and its acetate from the aerial part of Onopordum acanthium. Chemistry of Natural Compounds. 39 (3) (2003), 285-288.[7] L.J. Goad, T. Akihisha. Analysis of Sterols, Chapman & Hall, London (1997).[8] Phan Minh Giang, Văn Thị Thanh Huyền, Đỗ Thị Việt Hương. Thành phần sterol, glycerol ester và thiophen trong cành cây cúc tần (Pluchea indica L.) của Việt Nam. Tạp chí Khoa học Đại học Quốc gia Hà Nội. 34 (2) (2018), 78-82. [9] B. Sing, S.N. Ram, V.B. Pandey, V. K. Joshi, S. S. Gambhir. Studies on antiinflammatory activity of taraxasterol acetate from Echinops echinatus in rats and mice. Phytotherapy Research, 5 (3) (1991), 103-106.[10] Z. Krajcovicova, A. Vachálková, K. Horváthová. Taraxasterol and -sitosterol: New naturally compounds with chemoprotective/ chemopreventive effects. Neoplasma. 51 (2004), 407-414.[11] J. Wang, M. Huang, J. Yang, X. Ma, S. Zheng, S. Deng, Y. Huang, X. Yang, P. Zhao. Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter. Food & Nutrition Research, 61(1)(2017), 1364117.

scholarly journals Recent advances on oxadiazole motifs: Synthesis, reactions and biological activities

2020 ◽  
Vol 10 (5) ◽  
pp. 418
Author(s):  
Olayinka Oyewale Ajani ◽  
King T. Iyaye
Keyword(s):  
Industrial Development ◽  
Medicinal Chemistry ◽  
Light Emitting Diodes ◽  
Biological Activities ◽  
Light Emitting ◽  
Oxadiazole Derivatives ◽  
Synthetic Routes ◽  
High Yields ◽  
Synthesis Reactions ◽  
Very High

<p>1,3,4-oxadiazole derivatives have shown to have diverse and vast applications, from medicinal chemistry for the treatment and possible treatment of various ailments to its application in the industrial development when used as corrosion inhibitions and light emitting diodes. These diverse applications can be as a result of the numerous viable synthetic pathways illustrated in this review. 1,3,4-oxadiazoles can be synthesized in very high yields, using green approaches and having various life-changing applications. This review explores the various recent synthetic routes available for the development of 1,3,4-oxadiazoles and their biological activities.</p>

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