A two-hour synthesis of anti-Parkinson drug Safinamide Methanesulfonate

Synlett ◽  
2021 ◽  
Author(s):  
Vanessa Mayumi Higa ◽  
Alvaro Takeo Omori
Keyword(s):  
Microwave Irradiation ◽  
Ethyl Acetate ◽  
Real Time ◽  
Therapeutic Agents ◽  
Biologically Active ◽  
Green Solvents ◽  
Free Base ◽  
Chromatographic Purification ◽  
Purification Step ◽  
One Pot

The critical moment of COVID-19 outbreak requires a real time supply of therapeutic agents. Thus, the time economy in the synthesis of biologically active compounds has been increasingly decisive. In this work, we have developed a two-hour synthesis of anti-Parkinson drug safinamide methanesulfonate in 4 steps, with 64% overall yield. Microwave irradiation was used in the first three steps in a one-pot fashion. In fact, this presented protocol can provide Safinamide free base in one hour without chromatographic purification step. Also, green solvents such as methanol and ethyl acetate were applied.

Lewis Acid Promoted, One-Pot Synthesis of Fluoroquinolone Clubbed 1,3,4-Thiadiazole Motifs under Microwave Irradiation: Their Biological Activities

2020 ◽  
Vol 7 (1) ◽  
pp. 60-66
Author(s):  
Navin B. Patel ◽  
Rahul B. Parmar ◽  
Hetal I. Soni
Keyword(s):  
Reaction Time ◽  
Microwave Irradiation ◽  
Lewis Acid ◽  
Acid Catalyst ◽  
Antitubercular Activity ◽  
Biologically Active ◽  
High Yield ◽  
One Pot ◽  
One Pot Synthesis ◽  
Lewis Acid Catalyst

Background: A Lewis acid promoted efficient and facile procedure for one-pot synthesis of a novel series of fluoroquinolone clubbed with thiadiazoles motifs under microwave irradiation is described here. This technique has more advantages such as high yield, a clean procedure, low reaction time, simple work-up and use of Lewis acid catalyst. Objective: Our aim is to generate a biologically active 1,3,4- thiadiazole ring system by using a onepot synthesis method and microwave-assisted heating. High yield and low reaction time were the main purposes to synthesize bioactive fluoroquinolone clubbed 1,3,4- thiadiazole moiety. Methods: Fluoroquinolone Clubbed 1,3,4-Thiadiazole Motifs was prepared by Lewis acid promoted, one-pot synthesis, under microwave irradiation. All the synthesized molecules were determined by IR, 1H NMR, 13C NMR, and Mass spectra. The antimicrobial activity of synthesized compounds was examined against two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), and three fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus) using the MIC (Minimal Inhibitory Concentration) method and antitubercular activity H37Rv using L. J. Slope Method. Results: Lewis acid promoted, one-pot synthesis of Fluoroquinolone clubbed 1,3,4-Thiadiazole motifs under microwave irradiation is an extremely beneficial method because of its low reaction time and good yield. Some of these novel derivatives showed moderate to good in vitro antibacterial, antifungal, and antitubercular activity. Conclusion: One-pot synthesis of 1,3,4-Thiadiazole by using Lewis acid catalyst gives a good result for saving time and also getting more production of novel heterocyclic compounds with good antimicrobial properties via microwave heating method.

scholarly journals Microwave-assisted Eco-Friendly Synthesis and Antimicrobial Evaluation of Aryl-Triazole-1,3,4-Thiadiazols

2017 ◽  
Vol 1 (3) ◽  
pp. 17-22 ◽  
Author(s):  
Shalini Jaiswal ◽  
Smriti Dwivedi
Keyword(s):  
Microwave Irradiation ◽  
Organic Synthesis ◽  
Research Programme ◽  
Biologically Active Compounds ◽  
Solvent Free ◽  
Biologically Active ◽  
Aromatic Acid ◽  
One Pot ◽  
Active Compounds ◽  
Solvent Free Condition

Due to the growing awareness about environmental pollution and environmental legislation, recent years have witnessed a phenomenal increase in the application of microwave irradiation (MW) in organic synthesis. Heterocyclic compounds are abundant in nature and are of great significance to life because their structural subunits exist in many natural products such as vitamins, hormones, and antibiotics; hence, they have attracted considerable attention in the design of biologically active molecules and advanced organic chemistry. The application of molecular diversity technique to drug discovery is a multidisciplinary effort in organic synthesis. Medicinal chemistry concerns with the discovery, development, interpretation and the identification of mechanism of action of biologically active compounds at the molecular level. Encouraged by above reports and as part of our research programme for development of eco-friendly synthetic protocol for biologically active compounds as well as in pursuing of our work on new solvent-free cyclisation here we report the synthesis of aryl-triazalo -1, 3, 4-thidiazoles. The one-pot reaction of mercapto-s-triazole with aromatic acid using AlCl3 as a catalyst under microwave irradiation (2-3 min) and in solvent-free condition gave aryl-triazalo -1, 3, 4-thidiazoles with improved yield is described here. Keywords: Aryl-triazalo-1, 3, 4-thiadiazoles, Aromatic acid, AlCl3, cyclisation, S. aureus, E. coli, B. subtilis.

L-Cysteine Catalyzed Environmentally Benign One-pot Multicomponent Approach Towards the Synthesis of Dihydropyrano[2,3-c]pyrazole Derivatives

2020 ◽  
Vol 17 (6) ◽  
pp. 457-463 ◽  
Author(s):  
Sana Sikandar ◽  
Ameer Fawad Zahoor ◽  
Sajjad Ahmad ◽  
Muhammad Naveed Anjum ◽  
Mirza Nadeem Ahmad ◽  
...  
Keyword(s):  
Building Blocks ◽  
Biologically Active ◽  
Environmentally Benign ◽  
Pyrazole Derivatives ◽  
Green Solvents ◽  
Hydrazine Monohydrate ◽  
One Pot ◽  
Biological Potential ◽  
Wide Range ◽  
Substituted Benzaldehydes

Background: The pyrano[2,3-c]pyrazole derivatives are important building blocks of many biologically active compounds owing to their diverse biological potential for example, anti-inflammatory, anticancer, anti-microbial and anti-oxidant properties. Objective: Keeping in mind the wide range of applications of pyrano[2,3-c]pyrazoles, herein we intended to develop a novel synthetic methodology for dihydropyranopyrazoles. We were also interested in determining the influence of amino acids and dipeptides as a catalyst on the synthesis of pyrano[2,3-c]pyrazole derivatives. Methods: To achieve our objectives, we used a one-pot multi-component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and several substituted benzaldehydes by using different catalysts and solvents to synthesize our desired products in the presence of various catalysts. Results and Discussion: We found that optimal conditions for the preparation of pyrano[2,3-c]pyrazoles were L-cysteine (0.5 mol) in the presence of water:ethanol (9:1) at 90 °C. Various 1,4-dihydropyrano[2,3- c]pyrazoles were afforded by using several substituted benzaldehydes in 66-97% yields. Conclusion: We described a green and environmentally benign method to synthesize pyrano[2,3-c]pyrazoles in a one-pot four component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and different substituted benzaldehyde in the presence of L-cysteine in aqueous ethanol (9:1) at 90 oC. Excellent yields of the products, simple work-up, easily available starting materials, use of green solvents, naturally occurring catalyst, non-toxicity, non-chromatographic purification and environmentally benign reaction conditions are some main advantages of this protocol.

Metal-, and Organocatalyst-Free One-Pot Assembly of Chiral Aza-Tricyclic Molecules: Creating Six Contiguous Stereocenters from 2-D-Structures and an Amino Acid

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Amino Acid ◽  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Catalyst ◽  
Chiral Complex ◽  
Free Process

<p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> Practically, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for desired reactions. As a result, developing a method that enables rapid assembly of chiral complex molecules under metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward route to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“subcatalyst”) dual role of the intermediate enhances </a><a>the coordinational proximity of the chiral substrate and catalyst</a> in the key Aza-Michael/Michael cascade resulting in a substantial steric discrimination and an excellent overall diastereoselectivity. Whereas the “subcatalyst” (hidden catalyst) is not present in the reaction’s initial components, which renders a chiral catalyst-free process, it is strategically produced to promote sequential self-catalyzed reactions. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules and aid for the quest to create next generation of therapeutic agents.</p>

New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivativpes Bearing 1,2,4-oxadiazole Ring

2020 ◽  
Vol 17 (7) ◽  
pp. 525-534 ◽  
Author(s):  
Nevin Arıkan Ölmez ◽  
Faryal Waseer
Keyword(s):  
Microwave Irradiation ◽  
Room Temperature ◽  
Antimicrobial Activities ◽  
Phenyl Isocyanate ◽  
Single Step ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Thiourea Derivatives ◽  
Acyl Chlorides

Background: Urea, thiourea, and 1,2,4-oxadiazole compounds are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities. Objective: In this work, we provide a new series of potential biologically active compounds containing both 1,2,4-oxadiazole and urea/thiouprea moiety. Materials and Methods: Firstly, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (3a-j) were synthesized from the reaction of different substituted amidoximes (2a-j) and chloroacetyl chloride in the presence of pyridine by conventional and microwave-assisted methods. In the conventional method, 1,2,4-oxadiazoles were obtained in two steps. O-acylamidoximes obtained in the first step at room temperature were heated in toluene for an average of one hour to obtain 1,2,4-oxadiazoles. The yields varied from 70 to 96 %. 1,2,4-oxadiazoles were obtained under microwave irradiation in a single step in a 90-98 % yield at 160 °C in five minutes. 5-aminomethyl-3-aryl-1,2,4- oxadiazoles (5a-j) were obtained by Gabriel amine synthesis in two steps from corresponding 5-chloromethyl-3- aryl-1,2,4-oxadiazoles. Finally, twenty new urea (6a-j) and thiourea (7a-j) compounds bearing oxadiazole ring were synthesized by reacting 5-aminomethyl-3-aryl-1,2,4-oxadiazoles with phenyl isocyanate and isothiocyanate in tetrahydrofuran (THF) at room temperature with average yields (40-70%). Results and Discussions: An efficient and rapid method for the synthesis of 1,2,4-oxadiazoles from the reaction of amidoximes and acyl halides without using any coupling reagent under microwave irradiation has been developed, and twenty new urea/thiourea compounds bearing 1,2,4-oxadiazole ring have been synthesized and characterized. Conclusion: We have synthesized a new series of urea/thiourea derivatives bearing 1,2,4-oxadiazole ring. Also facile synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from amidoximes and acyl chlorides under microwave irradiation was reported. The compounds were characterized using FTIR, 1H NMR, 13C NMR, and elemental analysis techniques.

A Facile One-Pot Synthesis of 3-Methylbenzisoxazoles via a Key Intermediate of ortho-Ethoxyvinyl Nitroaryls by Domino Rearrangement and Their Anti- Inflammatory Activity

2020 ◽  
Vol 16 (8) ◽  
pp. 1161-1165
Author(s):  
Bashetti Nagaraju ◽  
Jagarlapudi V. Shanmukhakumar ◽  
Nareshvarma Seelam ◽  
Tondepu Subbaiah ◽  
Bethanamudi Prasanna
Keyword(s):  
Stannous Chloride ◽  
Biologically Active ◽  
Inflammatory Activity ◽  
Albino Rats ◽  
One Pot ◽  
Simple Method ◽  
Standard Drug ◽  
Entire Study ◽  
One Pot Synthesis ◽  
Anti Inflammatory

Background: Recently, there has been a lot of scientific interest in exploring the syntheses of oxygen and nitrogen-containing heterocyclic compounds due to their pharmacological activities. In addition, benzisoxazoles play a very important role in organic synthesis as key intermediates. Objective: In this paper, we focused on developing a novel synthetic route for biologically active arylisoxazoles under normal conditions, and simplified it to get high purities and yields, and also reported their anti-inflammatory activities. Method: An efficient and simple method has been explored for the synthesis of novel 3-methyl arylisoxazoles from o-nitroaryl halides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via Domino rearrangement in one pot synthesis. Result: We synthesized novel 3-methylarylisoxazoles from o-nitroarylhalides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via domino rearrangement. In this reduction, nitro group and ethoxy vinyl group change to the functional acyl ketones, followed by hetero cyclization. Here, the reaction proceeds without the isolation of intermediates like 2-acylnitroarenes and 2- acylanilines. All the synthesized compounds were completely characterized by the NMR and mass spectra. The compounds were also explored for their anti-inflammatory activity by carrageenan-induced inflammation in the albino rats (150-200 g) of either sex used in this entire study with the use of Diclofenac sodium as the standard drug. The initial evaluations identified leading targets with good to moderate anti-inflammatory activity. Conclusion: A simple, one-pot and convenient method has been explored for the synthesis of novel 3- methylarylisoxazoles with high purity and reaction yields. All the compounds 3a, 3c, 3d, 3f, 3g and 3h exhibited 51-64% anti-inflammatory activities.

Ethyl Acetate as a Pro-Reducing Agent in an One-Pot Reductive Deamination of Nitroanilines

2004 ◽  
Vol 77 (5) ◽  
pp. 1027-1028 ◽  
Author(s):  
Valeriy A. Bacherikov ◽  
May-Jane Wang ◽  
Shu-Yun Cheng ◽  
Ching-Huang Chen ◽  
Kuo-Tung Chen ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Reducing Agent ◽  
One Pot

scholarly journals Facile Bio-Fabrication of Ag-Cu-Co Trimetallic Nanoparticles and Its Fungicidal Activity against Candida auris

2021 ◽  
Vol 7 (1) ◽  
pp. 62 ◽  
Author(s):  
Majid Rasool Kamli ◽  
Vartika Srivastava ◽  
Nahid H. Hajrah ◽  
Jamal S. M. Sabir ◽  
Khalid Rehman Hakeem ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antimicrobial Properties ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Biologically Active ◽  
Phase Cell ◽  
Candida Auris ◽  
Medical Problems ◽  
One Pot ◽  
X Ray

Candida auris is an emergent multidrug-resistant pathogen that can lead to severe bloodstream infections associated with high mortality rates, especially in hospitalized individuals suffering from serious medical problems. As Candida auris is often multidrug-resistant, there is a persistent demand for new antimycotic drugs with novel antifungal action mechanisms. Here, we reported the facile, one-pot, one-step biosynthesis of biologically active Ag-Cu-Co trimetallic nanoparticles using the aqueous extract of Salvia officinalis rich in polyphenols and flavonoids. These medicinally important phytochemicals act as a reducing agent and stabilize/capping in the nanoparticles’ fabrication process. Fourier Transform-Infrared, Scanning electron microscopy, Transmission Electron Microscopy, Energy dispersive X-Ray, X-ray powder diffraction and Thermogravimetric analysis (TGA) measurements were used to classify the as-synthesized nanoparticles. Moreover, we evaluated the antifungal mechanism of as-synthesized nanoparticles against different clinical isolates of C. auris. The minimum inhibitory concentrations and minimum fungicidal concentrations ranged from 0.39–0.78 μg/mL and 0.78–1.56 μg/mL. Cell count and viability assay further validated the fungicidal potential of Ag-Cu-Co trimetallic nanoparticles. The comprehensive analysis showed that these trimetallic nanoparticles could induce apoptosis and G2/M phase cell cycle arrest in C. auris. Furthermore, Ag-Cu-Co trimetallic nanoparticles exhibit enhanced antimicrobial properties compared to their monometallic counterparts attributed to the synergistic effect of Ag, Cu and Co present in the as-synthesized nanoparticles. Therefore, the present study suggests that the Ag-Cu-Co trimetallic nanoparticles hold the capacity to be a lead for antifungal drug development against C. auris infections.

A water-soluble naphthalenediimide-containing hexacationic cage

2021 ◽  
Author(s):  
Hao Li ◽  
Feihe Huang ◽  
Shuai Fang ◽  
Errui Li ◽  
Dingsheng Zhu ◽  
...  
Keyword(s):  
Water Soluble ◽  
Chromatographic Purification ◽  
One Pot ◽  
Sn2 Reaction

A water-soluble cage containing three naphthalenediimide (NDI) units was synthesized in a one-pot manner without chromatographic purification, during which six irreversible C−N bonds formed simultaneously via SN2 reaction. The cage...

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