scholarly journals Toward a Practical, Two-Step Process for Molnupiravir from Cytidine

2021 ◽  
Author(s):  
Dinesh J. Paymode ◽  
Natarajan Vasudevan ◽  
Saeed Ahmad ◽  
Appasaheb L. Kadam ◽  
Flavio S. P. Cardoso ◽  
...  
Keyword(s):  
Total Concentration ◽  
Primary Alcohol ◽  
Environmentally Friendly ◽  
Active Pharmaceutical Ingredient ◽  
Crystalline Hydrate ◽  
Step Process ◽  
Work Up

<p>A two-step synthesis of molnupiravir (<b>1</b>) is presented. This work focuses on the development of practical reaction and purification conditions toward a manufacturing route. The sequence commences from highly available cytidine (<b>2</b>), and molnupiravir is formed through direct hydroxamination of the cytosine ring and esterification of the sugar’s primary alcohol without use of protecting or activating groups. A highly crystalline hydrate of <i>N</i>-hydroxycytidine (<b>3</b>) resulted in an easily purified intermediate, and a practical, off-the-shelf enzyme was selected for the acylation. The yield was increased through a chemically-promoted, selective ester cleavage which converted a by-product, molnupiravir isobutyryl oxime ester (<b>4</b>), into the final API. Both reactions proceed in >90% assay yield and crystallization procedures are used to afford intermediate and active pharmaceutical ingredient in purities above 99% with an overall yield of 60%. Excellent throughput and sustainability is achieved by limiting the total concentration to 7 volumes of solvent in the course of the two reactions with an overall PMI of 41 including work-up and isolation. Environmentally friendly solvents, water and 2-methyl tetrahydrofuran, enhance sustainability of the operation. </p>

scholarly journals Toward a Practical, Two-Step Process for Molnupiravir from Cytidine

2021 ◽  
Author(s):  
Dinesh J. Paymode ◽  
Natarajan Vasudevan ◽  
Saeed Ahmad ◽  
Appasaheb L. Kadam ◽  
Flavio S. P. Cardoso ◽  
...  
Keyword(s):  
Total Concentration ◽  
Primary Alcohol ◽  
Environmentally Friendly ◽  
Active Pharmaceutical Ingredient ◽  
Crystalline Hydrate ◽  
Step Process ◽  
Work Up

<p>A two-step synthesis of molnupiravir (<b>1</b>) is presented. This work focuses on the development of practical reaction and purification conditions toward a manufacturing route. The sequence commences from highly available cytidine (<b>2</b>), and molnupiravir is formed through direct hydroxamination of the cytosine ring and esterification of the sugar’s primary alcohol without use of protecting or activating groups. A highly crystalline hydrate of <i>N</i>-hydroxycytidine (<b>3</b>) resulted in an easily purified intermediate, and a practical, off-the-shelf enzyme was selected for the acylation. The yield was increased through a chemically-promoted, selective ester cleavage which converted a by-product, molnupiravir isobutyryl oxime ester (<b>4</b>), into the final API. Both reactions proceed in >90% assay yield and crystallization procedures are used to afford intermediate and active pharmaceutical ingredient in purities above 99% with an overall yield of 60%. Excellent throughput and sustainability is achieved by limiting the total concentration to 7 volumes of solvent in the course of the two reactions with an overall PMI of 41 including work-up and isolation. Environmentally friendly solvents, water and 2-methyl tetrahydrofuran, enhance sustainability of the operation. </p>

scholarly journals A Novel Telescoped Kilogram-Scale Process for Preparation of Obeticholic Acid

2021 ◽  
Vol 03 (02) ◽  
pp. e56-e64
Author(s):  
Cheng-Wei Li ◽  
Cai Wang ◽  
Chao Guo ◽  
Bin-Hua Lv ◽  
You-Fu Luo
Keyword(s):  
Environmentally Friendly ◽  
Scale Production ◽  
Obeticholic Acid ◽  
One Pot ◽  
Ketone Reduction ◽  
Step Process ◽  
Amide Hydrolysis ◽  
Work Up ◽  
Final Purification

A novel scalable four-step process has been developed to improve the synthesis of obeticholic acid (OCA). The key step of this process was the isolation of the amide intermediate, which underwent hydrogenation, basic epimerization, ketone reduction, and amide hydrolysis in a one-pot procedure. The use of efficient single recrystallization for the final purification in this process made the corresponding work-up procedure more concise and environmentally friendly. A kilogram-scale production of OCA following this process could achieve over 70% yield with all impurities controlled below 0.10%.

Synthesis of Eco-Friendly High PL Lifespan Manganese-Doped CuInZnS/ZnS QDs for White LED Applications

2020 ◽  
Vol 20 (10) ◽  
pp. 6286-6294
Author(s):  
Mukerem Helil Abib ◽  
Taotao Chen ◽  
Enze Xu ◽  
Man Wang ◽  
Yang Jiang
Keyword(s):  
White Light ◽  
Surface Passivation ◽  
Environmentally Friendly ◽  
White Led ◽  
One Pot ◽  
Step Process ◽  
The One ◽  
Mn Doped

Environmentally friendly and long PL lifespan Mn-doped CuInZnS (Mn:CIZS) and CuInZnS/ZnS (Mn:CIZS/ZnS) QDs, with respective red and yellow emissions, were synthesized using nontoxic precursors via a facile dual-step process based on the one-pot method. The resulting Mn:CIZS and Mn:CIZS/ZnS QDs exhibited confirmed strong red and yellow photoluminescence emissions at approximately 654 nm and 580 nm, respectively. The measured PL decay lifespan for the Mn: CIZS QDs is 2.52 μs due to well-organized surface passivation through the ZnS shell; the average PL lifespan for the Mn:CIZS/ZnS QDs is extended to 6.28 μs. Moreover, the WLEDs were composed of the Mn:CIZS/ZnS QDs. The resulting WLEDs offered admirable optical attributes, such as an excellent Ra of 89, a low Tc of 5075 K and radiant white light emanation at 60 mA functional current. Therefore, the outputs highlight the Mn:CIZS/ZnS QDs as hopeful cadmium-free resources for the interest of optoelectronics exploration.

scholarly journals Mg(HSO4)2/SiO2 as a Highly Efficient Catalyst for the Green Preparation of 2-Aryl-1,3-Dioxalanes/Dioxanes and Linear Acetals

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Fariba Jafari ◽  
Saeed Khodabakhshi
Keyword(s):  
Organic Solvents ◽  
Environmentally Friendly ◽  
Solvent Free ◽  
High Yield ◽  
Hydrogen Sulfate ◽  
Green Process ◽  
Efficient Catalyst ◽  
Solvent Free Conditions ◽  
Work Up ◽  
Environmentally Friendly Method

Silica-supported magnesium hydrogen sulfate has been used as a recyclable catalyst for the synthesis of some linear and cyclic aromatic acetals under solvent-free conditions. This environmentally friendly method has advantages, such as high yield of products, simple work-up procedure, and avoidance of the organic solvents, which will contribute in serving as a green process greatly.

A Clean One-pot Synthesis of 7-Amino-5-Aryl-6-Cyano-1,5-Dihydro-2H-Pyrano[2,3-d] Pyrimidine-2,4(3H)-Diones in Aqueous Media under Ultrasonic Irradiation

2005 ◽  
Vol 2005 (3) ◽  
pp. 162-163 ◽  
Author(s):  
Tong-Shou Jin ◽  
Li-Bin Liu ◽  
Ying Zhao ◽  
Tong-Shuang Li
Keyword(s):  
Ultrasonic Irradiation ◽  
Aqueous Media ◽  
Environmentally Friendly ◽  
Green Solvent ◽  
One Pot ◽  
One Pot Synthesis ◽  
Novel Approach ◽  
Work Up

A novel approach to the synthesis of 7-amino-5-aryl-6-cyano-1,5-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-diones in aqueous media under ultrasonic irradiation without catalyst is described. This method provides several advantages such as being environmentally friendly, simple work-up procedure and milder condition. In addition, water was chosen as a green solvent.

An Efficient Synthesis of Bis (Indolyl) Methanes Under Solvent Free Condition Using Silica Supported Polyphosphoric Acid (PPA-SiO2) as Recyclable Catalyst

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Sugat Kirti ◽  
Deepak Kumar ◽  
Navin Kumar Mogha ◽  
Virender Singh ◽  
Dhanraj T. Masram
Keyword(s):  
Phosphoric Acid ◽  
Polyphosphoric Acid ◽  
Environmentally Friendly ◽  
Solvent Free ◽  
Reusable Catalyst ◽  
Efficient Synthesis ◽  
Free Condition ◽  
Reaction Condition ◽  
Solvent Free Condition ◽  
Work Up

Silica supported poly-phosphoric acid (PPA-SiO2) has been utilized as an efficient and an environmentally friendly heterogeneous, reusable catalyst for the synthesis of bis(indolyl)methanes under solvent free condition. The significances of this protocol are mild reaction condition, excellent yield and simple work up procedure.

scholarly journals TOXIC METALS EXTRACTION DURING POTATO FERMENTATION

2017 ◽  
pp. 62-67 ◽  
Author(s):  
I. Sioma ◽  
А. Tashyrev ◽  
V. Govorukha ◽  
Y. Prekrasna
Keyword(s):  
Energy Source ◽  
Microbial Communities ◽  
Toxic Metals ◽  
Total Concentration ◽  
Environmentally Friendly ◽  
Natural Soil ◽  
Food Wastes ◽  
Combined Action ◽  
Metals Extraction

According to the thermodynamical prognosis developed by us the investigation of the interaction of Bacillus-Clostridium community and six representative metals was performed. To representative metals we refer: oxidisers (CrO42-), substitutes (Ni2+, Co2+) and combined action metals that combine the characteristics of both oxidizers and substitutes (Cu2+, Hg2+, Fe3+). The natural soil hydrogen-producing microbial communities appeared to be resistant to the metals in their high total concentration of 120 mg/l and also able to extract these metals from the solution (up to 96%). The obtained regularities are the base for the development of new combined biotechnologies, allowing to neutralize ecologically hazardous food wastes, treat metal contaminated sewages and simultaneously obtain environmentally friendly energy source – hydrogen.

scholarly journals Pyrazines Biosynthesis by Bacillus Strains Isolated from Natto Fermented Soybean

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1736
Author(s):  
Grzegorz Kłosowski ◽  
Dawid Mikulski ◽  
Katarzyna Pielech-Przybylska
Keyword(s):  
Bacillus Subtilis ◽  
Chemical Synthesis ◽  
Organic Compounds ◽  
Food Industry ◽  
Total Concentration ◽  
Environmentally Friendly ◽  
Two Cultures ◽  
Efficient Producer ◽  
Bacillus Strains ◽  
Producer Strains

Pyrazines are organic compounds with a varied, intense aroma of roasted nuts, occasionally with hints of baked potatoes, almonds, and others. As a result, they are used in the food industry as food flavorings. Biosynthesis of pyrazines using microorganisms in environmentally friendly conditions is an alternative to chemical synthesis. However, screening is required to isolate efficient producer strains for efficient biosynthesis of this compound. The study’s goal was to assess the ability of Bacillus subtilis cultures isolated from natto (fermented soybeans) to biosynthesize a broad range of alkylpyrazines. B. subtilis isolated cultures were found to be capable of producing 2-methylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, 2,3,5-trimethylpyrazine, and 2,3,5,6-tetramethylpyrazine. As a result of the screening, two cultures of B. subtilis capable of producing alkylpyrazines were isolated. At a total concentration of 3261 µg/L, the BcP4 strain primarily produced 2-methylpyrazine (690 µg/L), 2,3-dimethylpyrazine (680 µg/L), and 2,6-dimethylpyrazine (1891 µg/L). At a total concentration of 558 mg/L, the BcP21 strain produced 2,5-dimethylpyrazine (4.5 mg/L), 2,3,5-trimethylpyrazine (52.6 mg/L), and 2,3,5,6-tetramethylpyrazine (501.1 mg/L). The results show that different B. subtilis strains are predisposed to produce different alkylpyrazines.

scholarly journals Development of methods of determination of technological houses 3,5-dinitro- and 3,5-diaminobenzoics acids at synthesis of sodium amidotrіzоate

2019 ◽  
pp. 62-69
Author(s):  
T. A. Palchevska ◽  
O. P. Baula ◽  
V. I. Bessarabov ◽  
K. V. Palchevskyі
Keyword(s):  
Quantitative Analysis ◽  
Aqueous Solutions ◽  
Binary Mixtures ◽  
Total Concentration ◽  
Active Pharmaceutical Ingredient ◽  
Ultraviolet Region ◽  
Uv Spectrophotometry ◽  
Absorption Coefficients ◽  
Experimental Conditions ◽  
X Ray

Ionogenic contrast preparations, Triombrast, Urographin and Trasograph containing the active pharmaceutical ingredient (APhI), sodium amidotrizoate, have a positive experience in medical diagnosis. Qualitative control of intermediate products of each stage of AFI to prevent the possibility of technological toxic impurities – a mixture of 3,5-dinitro- and 3,5-diaminobenzoic acids (3,5-dNBK and 3,5-dABK) in the composition of the target product for safety X-ray contrast drugs in their application is a pressing issue today. The aim of the work – to develop a method for determining the technological impurities of 3,5-dNBK and 3,5-dABK acids in the synthesis of amidotrizoate sodium using UV spectrophotometry, which will allow to determine these impurities without their preliminary separation both in the inter-operative process control and in the finished product. The objects of study are aqueous solutions of 3,5-dNBK and 3,5-dABK acids, as well as their binary mixtures. The absorption spectra of the analytes were recorded using a Specord UV VIS spectrophotometer in the ultraviolet region. Calculations of the concentrations of the investigated acids in the composition of their binary compositions were performed according to the Vierordt's method. It is found that the absorption maxima of aqueous solutions of 3,5-dNBK and 3,5-dABK are at wavelengths of 240 nm and 218 nm; in the experimental conditions, the molar absorption coefficient for 3,5-dinitrobenzoic acid was the same (e1240 = e1218) and was equal to 17 940 ± 150. For solutions of 3,5-diaminobenzoic acid, the molar absorption coefficients were different: for a wavelength of 218 nm, the molar e2218 = 28 890 ± 220 and at a wavelength of 240 nm e2240 = 10 770 ± 80. Based on the Firordt method, taking into account the molar absorption coefficients of the investigated acids, we determined mathematical formulas for the quantitative analysis of the composition of mixtures at different ratios of analytes within their total concentration 1–6·10-5 M.            Spectrophotometric Vierordt's method of quantitative analysis of 3,5-dinitro- and 3,5-diaminobenzoic acids, as well as their binary mixtures in aqueous solutions can be applied in the industrial production of iodine-containing contrast agents, where in the first stages of synthesis, the corresponding nitrobenzoic acid is reduced.          Strict control of the possible amount of impurities in the first stage of synthesis of sodium amidotrizoate – the main active ingredient of ionic iodine-containing X-ray contrast drugs (Triombrast, Urografin, Trasograph) – will improve the quality of the final product and will allow to reduce the final product.

scholarly journals NH3(CH2)6NH3SiF6 catalyzed highly efficient synthesis of benzimidazoles, benzoxazoles, benzothiazoles, quinoxalines and pyrimidin-2-ones/thiones

2017 ◽  
Vol 5 (1) ◽  
pp. 60-71 ◽  
Author(s):  
Zakaria Benzekri ◽  
Houda Serrar ◽  
Said Boukhris ◽  
Ali Ouasri ◽  
Amina Hassikou ◽  
...  
Keyword(s):  
Reaction Times ◽  
Environmentally Friendly ◽  
Recyclable Catalyst ◽  
Efficient Synthesis ◽  
Highly Efficient ◽  
Work Up

Herein, we describe a simple, highly efficient and environmentally friendly protocol for the synthesis of benzimidazoles, benzoxazoles, benzothiazoles, 3,4-dihydropyrimidin-2-ones/ thiones and quinoxalines derivatives using hybrid crystal NH3(CH2)6NH3SiF6 as a catalyst. Use of recyclable catalyst, easy work-up procedure, excellent yields, short reaction times and scalability are the important practical features of the present protocol.

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