scholarly journals Multi-Catalytic Route for the Synthesis of (S)-Tembamide

Catalysts ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 822
Author(s):  
Laura Leemans ◽  
Marc D. Walter ◽  
Frank Hollmann ◽  
Anett Schallmey ◽  
Luuk M. van Langen
Keyword(s):  
Enantiomeric Excess ◽  
Initial Step ◽  
Building Blocks ◽  
Amino Alcohols ◽  
Hydrogenation Reaction ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Raney Ni ◽  
Synthetic Routes ◽  
Alcohol Derivative

Enantiopure β-amino alcohols constitute one of the most significant building blocks for the synthesis of active pharmaceutical ingredients. Despite the availability of a range of chiral β-amino alcohols from a chiral pool, there is a growing demand for new enantioselective synthetic routes to vicinal amino alcohols and their derivatives. In the present study, an asymmetric 2-step catalytic route that converts 4-anisaldehyde into a β-amino alcohol derivative, (S)-tembamide, with excellent enantiopurity (98% enantiomeric excess) has been developed. The recently published initial step consists in a concurrent biocatalytic cascade for the synthesis of (S)-4-methoxymandelonitrile benzoate. The O-benzoyl cyanohydrin is then converted to (S)-tembamide in a hydrogenation reaction catalyzed by Raney Ni. To achieve hydrogenation of the nitrile moiety with highest chemoselectivity and enantioretention, various parameters such as nature of the catalyst, reaction temperature and hydrogen pressure were studied. The reported strategy might be transferrable to the synthesis of other N-acyl-β-amino alcohols.

Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients

2019 ◽  
Vol 17 (6) ◽  
pp. 1552-1557 ◽  
Author(s):  
Renata M. Aguiar ◽  
Raquel A. C. Leão ◽  
Alejandro Mata ◽  
David Cantillo ◽  
C. Oliver Kappe ◽  
...  
Keyword(s):  
Amino Acids ◽  
Continuous Flow ◽  
Building Blocks ◽  
Active Pharmaceutical Ingredients ◽  
Enantiomerically Pure ◽  
Pharmaceutical Ingredients ◽  
Chiral Intermediates

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks.

Crystal structures of functional building blocks derived from bis(benzo[b]thiophen-2-yl)methane

2016 ◽  
Vol 72 (9) ◽  
pp. 679-684
Author(s):  
Felix Katzsch ◽  
Tobias Gruber ◽  
Edwin Weber
Keyword(s):  
Crystal Structures ◽  
Building Blocks ◽  
Dihedral Angles ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Crystal Packings

The syntheses of three bis(benzo[b]thiophen-2-yl)methane derivatives, namely bis(benzo[b]thiophen-2-yl)methanone, C17H10OS2, (I), 1,1-bis(benzo[b]thiophen-2-yl)-3-(trimethylsilyl)prop-2-yn-1-ol, C22H20OS2Si, (II), and 1,1-bis(benzo[b]thiophen-2-yl)prop-2-yn-1-ol, C19H12OS2, (III), are described and their crystal structures discussed comparatively. The conformation of ketone (I) and the respective analogues are rather similar for most of the compounds compared. This is true for the interplanar angles, the Caryl—Cbridge—Carylangles and the dihedral angles. The best resemblance is found for a bioisotere of (I),viz.2,2′-dinaphthyl ketone, (VII). By way of interest, the crystal packings also reveal similarities between (I) and (VII). In (I), the edge-to-face interactions seen between two napthyl residues in (VII) are substituted by S...π contacts between the benzo[b]thiophen-2-yl units in (I). In the structures of the bis(benzo[b]thiophen-2-yl)methanols,i.e.(II) and (III), the interplanar angles are also quite similar compared with analogues and related active pharmaceutical ingredients (APIs) containing the dithiophen-2-ylmethane scaffold, though the dihedral angles show a larger variability and produce unsymmetrical molecules.

Charge density and optical properties of multicomponent crystals containing active pharmaceutical ingredients or their analogues

2015 ◽  
Vol 71 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Marlena Gryl
Keyword(s):  
Optical Properties ◽  
Spatial Distribution ◽  
Charge Density ◽  
Optical Materials ◽  
Dipole Moments ◽  
Building Blocks ◽  
Active Pharmaceutical Ingredients ◽  
Design Strategies ◽  
Practical Applications ◽  
Pharmaceutical Ingredients

Active pharmaceutical ingredients (APIs), through their favourable donor/acceptor spatial distribution and synthon formation flexibility, are attractive building blocks in modern materials crystallography. The optical properties of a crystal strongly depend on two factors,i.e.the spatial distribution of molecules in the crystal structure and the electronic properties of molecular building blocks (dipole moments, polarizabilities, hyperpolarizabilities). Although the latter are easy to predict throughab initiocalculations, the former are not. Only a combination of experimental and theoretical charge density studies together with prediction and measurement of optical properties enable full analysis of the obtained functional material in terms of its usefulness in practical applications. This article presents design strategies of optical materials based on selected pharmaceutical molecules. Factors that contribute to molecular recognition in the four selected polar/chiral crystal phases (derived through charge density and Hirshfeld surfaces analysis) have been determined. Theoretically predicted optical properties of the molecular/ionic building blocks as well as bulk effects have been confirmed experimentally. This research is a first step in the design of novel optical materials based on push–pull molecules and APIs.

scholarly journals Main group mechanochemistry

2017 ◽  
Vol 13 ◽  
pp. 2068-2077 ◽  
Author(s):  
Agota A Gečiauskaitė ◽  
Felipe García
Keyword(s):  
Metal Oxides ◽  
Organic Compounds ◽  
Coordination Compounds ◽  
Short Review ◽  
Main Group ◽  
Organometallic Complexes ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
The Past ◽  
Synthetic Routes

Over the past decade, mechanochemistry has emerged as a powerful methodology in the search for sustainable alternatives to conventional solvent-based synthetic routes. Mechanochemistry has already been successfully applied to the synthesis of active pharmaceutical ingredients (APIs), organic compounds, metal oxides, coordination compounds and organometallic complexes. In the main group arena, examples of synthetic mechanochemical methodologies, whilst still relatively sporadic, are on the rise. This short review provides an overview of recent advances and achievements in this area that further validate mechanochemistry as a credible alternative to solution-based methods for the synthesis of main group compounds and frameworks.

scholarly journals SELF-SUFFICIENCY IN MANUFACTURE OF APIS AND INTERMEDIATES IS A NECESSITY FOR THE INDIAN PHARMACEUTICAL INDUSTRY

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (04) ◽  
pp. 5-6
Author(s):  
Shreerang Joshi ◽  
Keyword(s):  
Pharmaceutical Industry ◽  
Raw Materials ◽  
Building Blocks ◽  
Dosage Forms ◽  
Considerable Extent ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Self Sufficiency ◽  
Dear Reader ◽  
Indian Pharmaceutical Industry

Dear Reader, Active Pharmaceutical Ingredients (APIs) are key raw materials to produce pharmaceutical finished dosage forms like tablets, capsules, syrups, ointments etc. Swift growth in new innovations is prodding the interest for generic active pharmaceutical ingredients manufacturers worldwide with the expanded import of key starting materials (KSMs) and building blocks from the emerging markets. The focus of Indian pharmaceutical industry in last two decades has moved towards finished formulations, ignoring in-house manufacture of APIs to a considerable extent.

scholarly journals Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods

2021 ◽  
Author(s):  
Stefan Simić ◽  
Erna Zukić ◽  
Luca Schmermund ◽  
Kurt Faber ◽  
Christoph K. Winkler ◽  
...  
Keyword(s):  
Small Molecule ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Synthetic Routes

scholarly journals Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

2021 ◽  
Vol 17 ◽  
pp. 932-963
Author(s):  
Asha Budakoti ◽  
Pradip Kumar Mondal ◽  
Prachi Verma ◽  
Jagadish Khamrai
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Stereoselective Synthesis ◽  
Building Blocks ◽  
Active Pharmaceutical Ingredients ◽  
Prins Reaction ◽  
Prins Cyclization ◽  
Pharmaceutical Ingredients ◽  
New Strategies ◽  
Made In

Functionalized tetrahydropyran (THP) rings are important building blocks and ubiquitous scaffolds in many natural products and active pharmaceutical ingredients (API). Among various established methods, the Prins reaction has emerged as a powerful technique in the stereoselective synthesis of the tetrahydropyran skeleton with various substituents, and the strategy has further been successfully applied in the total synthesis of bioactive macrocycles and related natural products. In this context, hundreds of valuable contributions have already been made in this area, and the present review is intended to provide the systematic assortment of diverse Prins cyclization strategies, covering the literature reports of the last twenty years (from 2000 to 2019), with an aim to give an overview on exciting advancements in this area and designing new strategies for the total synthesis of related natural products.

Reversed-Phase High Performance Liquid Chromatographic Analysis of Three First Line Anti-Tuberculosis Drugs

2019 ◽  
Vol 69 (12) ◽  
pp. 3590-3592
Author(s):  
Nela Bibire ◽  
Romeo Iulian Olariu ◽  
Luminita Agoroaei ◽  
Madalina Vieriu ◽  
Alina Diana Panainte ◽  
...  
Keyword(s):  
High Performance ◽  
Biological Fluids ◽  
Gradient Elution ◽  
High Performance Liquid Chromatographic ◽  
Reversed Phase ◽  
Assay Method ◽  
Active Pharmaceutical Ingredients ◽  
First Line ◽  
Pharmaceutical Ingredients ◽  
Liquid Chromatographic

Active pharmaceutical ingredients such as isoniazid, pyrazinamide and rifampicin are among the most important first-line anti-tuberculosis drugs. A simple, rapid and sensitive reversed phase-high performance liquid chromatographic assay method for the simultaneous determination of isoniazid, pyrazinamide and rifampicin has been developed. Separation of the interest compounds was achieved in a 10 min chromatographic run in gradient elution mode on a Zorbax SB-C18 stainless steel column (150 � 4 mm, 5 mm) using a guard column containing the same stationary phase. The gradient elution was carried out with a mobile phase of 10% CH3CN aqueous solution for channel A and 50% CH3CN in pH = 6.8 phosphate buffer (20 mM), to which 1.5 mL triethylamine were added for channel B. Quantification of the analyzed substances was carried out spectrophotometrically at 269 nm. Detection limits of 0.48 mg/L for isoniazid, 0.52 mg/L for pyrazinamide and 0.48 mg/L for rifampicin were established for the developed assay method. The present work showed that the proposed analysis method was advantageous for simple and rapid analysis of the active pharmaceutical ingredients in pharmaceuticals and biological fluids.

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

2020 ◽  
Vol 24 (21) ◽  
pp. 2475-2497
Author(s):  
Andrea Verónica Rodríguez-Mayor ◽  
German Jesid Peralta-Camacho ◽  
Karen Johanna Cárdenas-Martínez ◽  
Javier Eduardo García-Castañeda
Keyword(s):  
Chemical Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Heterogeneous Environments ◽  
Phase Synthesis ◽  
Low Concentrations ◽  
Biological Sources ◽  
Synthetic Routes ◽  
The Impact ◽  
Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

Design, Synthesis and Bioactivity of Core 1 O-glycan and its Derivative on Human Gut Microbiota

2019 ◽  
Vol 16 (12) ◽  
pp. 1348-1353
Author(s):  
Huanhuan Qu ◽  
Baixue Li ◽  
Jingyi Yang ◽  
Huaiwen Liang ◽  
Meixia Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Initial Step ◽  
Building Blocks ◽  
Glycan Structure ◽  
Human Gut ◽  
Design Synthesis ◽  
The Core ◽  
Human Gut Microbiota ◽  
Biochemical Studies ◽  
Gut Symbionts

Background: Disaccharide core 1 (Galβ1-3GalNAc) is a common O-glycan structure in nature. Biochemical studies have confirmed that the formation of the core 1 structure is an important initial step in O-glycan biosynthesis and it is of great importance for human body. Objective: Our study will provide meaningful and useful sights for O-glycan synthesis and their bioassay. And all the synthetic glycosides would be used as intermediate building blocks in the scheme developed for oligosaccharide construction. Methods: In this article, we firstly used chemical procedures to prepare core 1 and its derivative, and a novel disaccharide was efficiently synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR and MS. Then we employed three human gut symbionts belonging to Bacteroidetes, a predominantphyla in the distal gut, as models to study the bioactivity of core 1 and its derivative on human gut microbiota. Results: According to our results, both core 1 and derivative could support the growth of B. fragilis, especially the core 1 derivative, while failed to support the growth of B. thetaiotaomicron and B. ovatus. Conclusion: This suggested that the B. fragilis might have the specificity glycohydrolase to cut the glycosidic bond for acquiring monosaccharide.

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