scholarly journals Acyl(imidoyl)ketenes: Reactive Bidentate Oxa/Aza-Dienes for Organic Synthesis

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1509
Author(s):  
Ekaterina A. Lystsova ◽  
Ekaterina E. Khramtsova ◽  
Andrey N. Maslivets
Keyword(s):  
Drug Discovery ◽  
Organic Synthesis ◽  
High Selectivity ◽  
Building Blocks ◽  
Atom Economy ◽  
Thermal Generation ◽  
Modern Drug ◽  
Small Molecule Libraries ◽  
Intermolecular Reactions ◽  
High Yields

Polyfunctional building blocks are essential for the implementation of diversity-oriented synthetic strategies, highly demanded in small molecule libraries’ design for modern drug discovery. Acyl(imidoyl)ketenes are highly reactive organic compounds, bearing both oxa- and aza-diene moieties, conjugated symmetrically to the ketene fragment, enabling synthesis of various skeletally diverse heterocycles on their basis. The highlights of reactions utilizing acyl(imidoyl)ketenes are high yields, short reaction time (about several minutes), high selectivity, atom economy, and simple purification procedures, which benefits the drug discovery. The present review focuses on the approaches to thermal generation of acyl(imidoyl)ketenes, patterns of their immediate transformations via intra- and intermolecular reactions, including the reactions of cyclodimerization, in which either symmetric or dissymmetric heterocycles can be formed. Recent advances in investigations on mechanisms, identifications of intermediates, and chemo- and regioselectivity of reactions with participation of acyl(imidoyl)ketenes are also covered.

scholarly journals Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

2019 ◽  
Vol 15 ◽  
pp. 874-880
Author(s):  
Razieh Navari ◽  
Saeed Balalaie ◽  
Saber Mehrparvar ◽  
Fatemeh Darvish ◽  
Frank Rominger ◽  
...  
Keyword(s):  
Room Temperature ◽  
High Selectivity ◽  
Domino Reaction ◽  
Primary Amines ◽  
Efficient Synthesis ◽  
Atom Economy ◽  
Reaction Conditions ◽  
Efficient Approach ◽  
Three Component Reaction ◽  
High Yields

An efficient approach for the synthesis of pyrazolopyridines containing the aminochromane motif through a base-catalyzed cyclization reaction is reported. The synthesis was carried out through a three-component reaction of (arylhydrazono)methyl-4H-chromen-4-one, malononitrile, primary amines in the presence of Et3N at room temperature. However, carrying out the reaction under the same conditions without base led to a fused chromanyl-cyanopyridine. High selectivity, high atom economy, and good to high yields in addition to mild reaction conditions are the advantages of this approach.

Complex Polycycles from Simple Propargyl Alcohols through Ruthenium-Catalyzed Cascade Reactions and One-Pot Procedures

Synthesis ◽  
2017 ◽  
Vol 50 (04) ◽  
pp. 742-752 ◽  
Author(s):  
Elisabeth Jäckel ◽  
Julia Kaufmann ◽  
Edgar Haak
Keyword(s):  
Drug Discovery ◽  
Organic Synthesis ◽  
High Selectivity ◽  
Multiple Bond ◽  
Cascade Reactions ◽  
Kb Cells ◽  
One Pot ◽  
Bond Forming ◽  
Common Precursor ◽  
Propargyl Alcohols

Multiple bond-forming cascade transformations and one-pot procedures are valuable tools in organic synthesis and drug discovery. These atom-economical processes provide rapid access to natural product-like scaffolds from simple precursors. Herein, we report on ruthenium-catalyzed one-pot conversions of simple 1-alkenyl propargyl alcohols with cyclic 3-ketolactones and dienophiles. Thereby, structurally diverse fused polycycles and functionalized bicyclic structures are accessible from a common precursor with high selectivity. Some of the new drug-like molecules exhibit cytotoxic activity against KB cells.

scholarly journals Diversity-Oriented Synthesis: Amino Acetophenones as Building Blocks for the Synthesis of Natural Product Analogs

2021 ◽  
Vol 14 (11) ◽  
pp. 1127
Author(s):  
Mathias Eymery ◽  
Viet-Khoa Tran-Nguyen ◽  
Ahcène Boumendjel
Keyword(s):  
Drug Discovery ◽  
Natural Product ◽  
Organic Synthesis ◽  
Building Blocks ◽  
Structural Features ◽  
The Other ◽  
Pharmacological Properties ◽  
Diversity Oriented Synthesis ◽  
Fully Integrated ◽  
Lead Compounds

Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy in organic synthesis and is fully integrated in various drug discovery processes. On the other hand, natural products with multiple relevant pharmacological properties have been extensively investigated as scaffolds for ligand-based drug design. In this article, we report the amino dimethoxyacetophenones that can be easily synthesized and scaled up from the commercially available 3,5-dimethoxyaniline as valuable starting blocks for the DOS of natural product analogs. More focus is placed on the synthesis of analogs of flavones, coumarins, azocanes, chalcones, and aurones, which are frequently studied as lead compounds in drug discovery.

scholarly journals In-Silico Drug Design: A revolutionary approach to change the concept of current Drug Discovery Process

2013 ◽  
Vol 1 (02) ◽  
pp. 60-73 ◽  
Author(s):  
Lakhyajit Boruah ◽  
Aparoop Das ◽  
Lalit Mohan Nainwal ◽  
Neha Agarwal ◽  
Brajesh Shankar
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
In Silico ◽  
Traditional Approach ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Chemical Library ◽  
In Silico Drug Design ◽  
Modern Drug ◽  
Small Molecule Libraries

Computational methods play a central role in modern drug discovery process. It includes the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity as well as selectivity of hits and improving the physicochemical properties of the lead compounds. In this review article, computational drug designing approaches have been elucidated and discussed. The key considerations and guidelines for virtual chemical library design and whole drug discovery process. Traditional approach for discovery of a new drug is a costly and time consuming affair besides not being so productive. A number of potential reasons witness choosing the In-silico method of drug design to be a more wise and productive approach. There is a general perception that applied science has not kept pace with the advances of basic science. Therefore, there is a need for the use of alternative tools to get answers on efficacy and safety faster, with more certainty and at lower cost. In-silico drug design can play a significant role in all stages of drug development from the initial lead designing to final stage clinical development.

Ultrasound-Activated Atom-Economical Approach to the Synthesis of Highly Substituted Pyrrolidin-2-ones through a Four-Component Ugi/5-endo-trig Intramolecular Radical Cyclization Reaction

Synlett ◽  
2020 ◽  
Vol 31 (09) ◽  
pp. 871-877
Author(s):  
Saeed Balalaie ◽  
Atena Nashta Rahimi ◽  
Helya Janatian Ghazvini ◽  
Frank Rominger ◽  
Hossein Zahedian Tejeneki ◽  
...  
Keyword(s):  
High Selectivity ◽  
Reaction Times ◽  
Radical Cyclization ◽  
Ugi Reaction ◽  
Cyclization Reaction ◽  
Atom Economy ◽  
Reaction Sequence ◽  
Single Product ◽  
Subsequent Transformation ◽  
High Yields

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.

scholarly journals Phytochemical Properties and Pharmcological Activities of Nicotiana Tabacum: A Review

2013 ◽  
Vol 1 (02) ◽  
pp. 74-82
Author(s):  
Aarti Rawat ◽  
Rakesh Roshan Mali
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
In Silico ◽  
Traditional Approach ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Chemical Library ◽  
Modern Drug ◽  
Small Molecule Libraries ◽  
Hit Identification

Computational methods play a central role in modern drug discovery process. It includes the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity as well as selectivity of hits and improving the physicochemical properties of the lead compounds. In this review article, computational drug designing approaches have been elucidated and discussed. The key considerations and guidelines for virtual chemical library design and whole drug discovery process. Traditional approach for discovery of a new drug is a costly and time consuming affair besides not being so productive. A number of potential reasons witness choosing the In-silico method of drug design to be a more wise and productive approach. There is a general perception that applied science has not kept pace with the advances of basic science. Therefore, there is a need for the use of alternative tools to get answers on efficacy and safety faster, with more certainty and at lower cost. In-silico drug design can play a significant role in all stages of drug development from the initial lead designing to final stage clinical development.

scholarly journals The Development of Biocatalysis as a Tool for Drug Discovery

2020 ◽  
Vol 74 (5) ◽  
pp. 368-377 ◽  
Author(s):  
Jenny Schwarz ◽  
Katrin Rosenthal ◽  
Radka Snajdrova ◽  
Matthias Kittelmann ◽  
Stephan Lütz
Keyword(s):  
Drug Discovery ◽  
Enzymatic Synthesis ◽  
High Selectivity ◽  
Drug Research ◽  
New Products ◽  
Building Blocks ◽  
Process Conditions ◽  
The Past ◽  
Potential Applications ◽  
Industrial Use

Enzymes are versatile biocatalysts capable of performing selective reactions. The advantages of enzymes in comparison to classical chemistry including chemical catalysts are the generally milder process conditions and avoidance of harmful reactants. Their high selectivity and specificity are especially beneficial for the enzymatic synthesis of new products with potential applications in drug research. Therefore, in the past decades, the utilization of isolated enzymes or whole-cell biocatalysts has spread through a growing number of biotechnological industries. The applications comprise the production of chiral building blocks for the pharmaceutical and fine chemical industry, the enzymatic synthesis of drug metabolites for testing of toxicity, function, biological activity, degradation and the production of biocatalytically modified natural products, which all play a role in drug discovery. Especially Oreste Ghisalba's contributions, which paved the way for the industrial use of enzymes, will be considered in this review.

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

2020 ◽  
Author(s):  
Aleksandra Balliu ◽  
Aaltje Roelofje Femmigje Strijker ◽  
Michael Oschmann ◽  
Monireh Pourghasemi Lati ◽  
Oscar Verho
Keyword(s):  
Carboxylic Acid ◽  
Building Blocks ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
High Yields ◽  
Vinyl Iodides ◽  
Initial Results

<p>In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both <i>cis</i>- and <i>trans</i>-configured carboxylic acid building blocks from the C–H alkenylation products.</p>

Insulating Composites Made from Sulfur, Canola Oil, and Wool

2020 ◽  
Author(s):  
Israa Bu Najmah ◽  
Nicholas Lundquist ◽  
Melissa K. Stanfield ◽  
Filip Stojcevski ◽  
Jonathan A. Campbell ◽  
...  
Keyword(s):  
Tensile Strength ◽  
Canola Oil ◽  
Building Blocks ◽  
Atom Economy ◽  
Flame Resistance ◽  
Sustainable Building ◽  
Second Stage ◽  
Wool Fibers ◽  
Insulating Properties ◽  
Polysulfide Polymer

An insulating composite was made from the sustainable building blocks wool, sulfur, and canola oil. In the first stage of the synthesis, inverse vulcanization was used to make a polysulfide polymer from the canola oil triglyceride and sulfur. This polymerization benefits from complete atom economy. In the second stage, the powdered polymer is mixed with wool, coating the fibers through electrostatic attraction. The polymer and wool mixture is then compressed with mild heating to provoke S-S metathesis in the polymer, which locks the wool in the polymer matrix. The wool fibers impart tensile strength, insulating properties, and flame resistance to the composite. All building blocks are sustainable or derived from waste and the composite is a promising lead on next-generation insulation for energy conservation.

Sign in / Sign up

Export Citation Format

Share Document