scholarly journals Synthesis of Chromeno[3,4-b]piperazines by an Enol-Ugi/Reduction/Cyclization Sequence

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1287
Author(s):  
Ana Bornadiego ◽  
Ana G. Neo ◽  
Carlos F. Marcos
Keyword(s):  
Drug Discovery ◽  
Building Blocks ◽  
Ugi Reaction ◽  
The Novel ◽  
Constrained Peptides ◽  
Geometrically Constrained

Keto piperazines and aminocoumarins are privileged building blocks for the construction of geometrically constrained peptides and therefore valuable structures in drug discovery. Combining these two heterocycles provides unique rigid polycyclic peptidomimetics with drug-like properties including many points of diversity that could be modulated to interact with different biological receptors. This work describes an efficient multicomponent approach to condensed chromenopiperazines based on the novel enol-Ugi reaction. Importantly, this strategy involves the first reported post-condensation transformation of an enol-Ugi adduct.

Total Synthesis of Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Based Drug Discovery

2019 ◽  
Author(s):  
Primali Navaratne ◽  
Jenny Wilkerson ◽  
Kavindri Ranasinghe ◽  
Evgeniya Semenova ◽  
Lance McMahon ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Total Synthesis ◽  
Ground State ◽  
Chemical Space ◽  
Modern Medicine ◽  
The Novel ◽  
Pharmaceutical Development ◽  
Bioactive Component ◽  
Axially Chiral ◽  
New Directions

<div> <div> <div> <p>Phytocannabinoids, molecules isolated from cannabis, are gaining attention as promising leads in modern medicine, including pain management. Considering the urgent need for combating the opioid crisis, new directions for the design of cannabinoid-inspired analgesics are of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural (and unknown) isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are multiple reasons for thinking this: (a) ax-CBNs would have ground-state three-dimensionality akin to THC, a key bioactive component of cannabis, (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability, and (c) atropisomerism with respect to phytocannabinoids is unexplored “chemical space.” Herein we report a scalable total synthesis of ax-CBNs, examine physical properties experimentally and computationally, and provide preliminary behavioral and analgesic analysis of the novel scaffolds. </p> </div> </div> </div>

Synthesis of sp3-Enriched β-Fluoro Sulfonyl Chlorides

Synthesis ◽  
2020 ◽  
Author(s):  
Oleksandr O. Grygorenko ◽  
Rustam Gurbanov ◽  
Andriy Sokolov ◽  
Sergey Golovach ◽  
Kostiantyn Melnykov ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Double Bond ◽  
Building Blocks ◽  
Protecting Groups ◽  
Sulfonyl Chlorides ◽  
Wide Range ◽  
Cyclic Compounds

AbstractA three-step approach to the synthesis of sp3-enriched β-fluoro sulfonyl chlorides starting from alkenes is reported. The method was successfully applied to a wide range of acyclic and cyclic substrates, bearing either an exocyclic or an endocyclic double bond. The procedure worked with a wide range of substrates and tolerated a number of functional and protecting groups. Moreover, the target cyclic compounds were obtained as single cis diastereomers on a multigram scale. The title compounds are promising building blocks for drug discovery that can be used to obtain sp3-enriched β-fluoro and α,β-unsaturated sulfonamides.

scholarly journals Sophorolipid-Based Oligomers as Polyol Components for Polyurethane Systems

Polymers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2001
Author(s):  
Maresa Sonnabend ◽  
Suzanne G. Aubin ◽  
Annette M. Schmidt ◽  
Marc C. Leimenstoll
Keyword(s):  
Special Property ◽  
Building Blocks ◽  
Conservation Of Resources ◽  
The Novel ◽  
Carbon Footprints ◽  
Proper Design ◽  
Chemical Products ◽  
Hydroxyl Fatty Acids ◽  
New Applications ◽  
Novel Products

Due to reasons of sustainability and conservation of resources, polyurethane (PU)-based systems with preferably neutral carbon footprints are in increased focus of research and development. The proper design and development of bio-based polyols are of particular interest since such polyols may have special property profiles that allow the novel products to enter new applications. Sophorolipids (SL) represent a bio-based toolbox for polyol building blocks to yield diverse chemical products. For a reasonable evaluation of the potential for PU chemistry, however, further investigations in terms of synthesis, derivatization, reproducibility, and reactivity towards isocyanates are required. It was demonstrated that SL can act as crosslinker or as plasticizer in PU systems depending on employed stoichiometry. (ω-1)-hydroxyl fatty acids can be derived from SL and converted successively to polyester polyols and PU. Additionally, (ω-1)-hydroxyl fatty acid azides can be prepared indirectly from SL and converted to A/B type PU by Curtius rearrangement.

scholarly journals Synthetically Accessible Virtual Inventory (SAVI)

2020 ◽  
Author(s):  
Hitesh Patel ◽  
Wolf Ihlenfeldt ◽  
Philip Judson ◽  
Yurii S. Moroz ◽  
Yuri Pevzner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chemical Synthesis ◽  
Programming Languages ◽  
Expert Knowledge ◽  
Scoring Systems ◽  
Building Blocks ◽  
Single Step

We have made available a database of over 1 billion compounds predicted to be easily synthesizable. They have been created by a set of transforms based on an adaptation and extension of the CHMTRN/PATRAN programming languages describing chemical synthesis expert knowledge, which originally stem from the LHASA project. The chemoinformatics toolkit CACTVS was used to apply a total of 53 transforms to about 150,000 readily available building blocks (enamine.net). Only single-step, two-reactant syntheses were calculated for this database even though the technology can execute multi-step reactions. The possibility to incorporate scoring systems in CHMTRN allowed us to subdivide the database of 1.75 billion compounds in sets according to their predicted synthesizability, with the most-synthesizable class comprising 1.09 billion synthetic products. Properties calculated for all SAVI products show that the database should be well-suited for drug discovery. It is being made publicly available for free download from https://cactus.nci.nih.gov/download/savi_download/.

Contribution to PNA-RNA Chimera Synthesis: One-Pot Microwave-Assisted Ugi Reaction to Obtain Dimeric Building Blocks

2016 ◽  
Vol 2017 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Reuben Ovadia ◽  
Clémence Mondielli ◽  
Jean-Jacques Vasseur ◽  
Carine Baraguey ◽  
Karine Alvarez
Keyword(s):  
Building Blocks ◽  
Ugi Reaction ◽  
One Pot ◽  
Microwave Assisted

scholarly journals Cover Feature: Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery (Chem. Eur. J. 47/2018)

2018 ◽  
Vol 24 (47) ◽  
pp. 12102-12102
Author(s):  
Roman M. Bychek ◽  
Vadym V. Levterov ◽  
Iryna V. Sadkova ◽  
Andrey A. Tolmachev ◽  
Pavel K. Mykhailiuk
Keyword(s):  
Drug Discovery ◽  
Building Blocks

Glycosylated α-Azido Amino Acids: Versatile Intermediates in the Synthesis of Neoglycoconjugates

Synlett ◽  
2018 ◽  
Vol 29 (07) ◽  
pp. 904-907 ◽  
Author(s):  
Trinidad Velasco-Torrijos ◽  
Róisín O’Flaherty
Keyword(s):  
Amino Acids ◽  
Drug Discovery ◽  
Building Blocks ◽  
Sensor Development ◽  
Galactosyl Ceramide

A series of glycosylated α-azido amino acids was synthesized as precursors for neoglycoconjugates, a class of important biomolecules for drug discovery, and sensor development. The synthetically challenging 1,2-cis α-galactosylated species described herein were designed as building blocks in the synthesis of analogues of α-galactosyl ceramide, a potent immunomodulator. A benzyl-protected 1,2,3-triazolyl α-galactosyl-l-serine derivative was prepared using copper azide alkyne cycloaddition to showcase the potential of glycosylated α-azido amino acids in neoglycoconjugate design.

Diastereoselective Synthesis of 2-Phenyl-3-(trifluoromethyl)piperazines as Building Blocks for Drug Discovery

2014 ◽  
Vol 79 (12) ◽  
pp. 5887-5894 ◽  
Author(s):  
María Sánchez-Roselló ◽  
Oscar Delgado ◽  
Natalia Mateu ◽  
Andrés A. Trabanco ◽  
Michiel Van Gool ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Building Blocks ◽  
Diastereoselective Synthesis

scholarly journals The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

2020 ◽  
Vol 74 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Kris Meier ◽  
Sven Bühlmann ◽  
Josep Arús-Pous ◽  
Jean-Louis Reymond
Keyword(s):  
Drug Discovery ◽  
Medicinal Chemistry ◽  
Organic Molecules ◽  
Chemical Space ◽  
Building Blocks ◽  
Chiral Molecules ◽  
Hydrogen Atoms ◽  
Quaternary Centers ◽  
Medical Needs ◽  
Unmet Medical Needs

Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

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