Recent Advances in the Synthetic Chemistry of Bicyclo[1.1.1]pentane

Synlett ◽  
2018 ◽  
Vol 30 (01) ◽  
pp. 1-11 ◽  
Author(s):  
Junichiro Kanazawa ◽  
Masanobu Uchiyama
Keyword(s):  
Water Solubility ◽  
Chemical Space ◽  
Direct Synthesis ◽  
Three Dimensional ◽  
High Water ◽  
Synthetic Chemistry ◽  
Drug Candidates ◽  
Recent Advances ◽  
Wide Range ◽  
Phenyl Rings

Utilization of three-dimensional cyclic scaffolds is important in modern drug discovery, both to provide greater opportunities for optimizing drug candidates and to expand the available chemical space of drugs. Among these scaffolds, bicyclo[1.1.1]pentane (BCP) is a high-value bioisostere for 1,4-disubstituted phenyl rings, internal alkynes, and the tert-butyl group, generally offering high passive permeability, high water solubility, and improved metabolic stability. However, the lack of methods for functionalizing BCP remains a significant challenge, and in particular, a versatile strategy for synthesizing a wide range of unsymmetrically 1,3-difunctionalized BCP derivatives has been lacking. In this account, we review recent advances in the synthetic chemistry of BCP, focusing especially on our recently developed radical multicomponent carboamination of [1.1.1]propellane.1 Introduction2 Overview of the Synthetic Chemistry of [1.1.1]Propellane, the Most Promising Precursor of Bicyclo[1.1.1]pentane3 Recent Advances in the Synthetic Chemistry of Unsymmetrically 1,3-Disubstituted Bicyclo[1.1.1]pentane Derivatives4 Radical Multicomponent Carboamination of [1.1.1]Propellane Permits Direct Synthesis of 3-Substituted Bicyclo[1.1.1]pent-1-ylamine Derivatives5 Conclusion

scholarly journals Application of Dendrimers for Treating Parasitic Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 343
Author(s):  
Veronica Folliero ◽  
Carla Zannella ◽  
Annalisa Chianese ◽  
Debora Stelitano ◽  
Annalisa Ambrosino ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Water Solubility ◽  
Parasitic Infection ◽  
Three Dimensional ◽  
Medical Knowledge ◽  
High Ratio ◽  
Molecular Volume ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Wide Range

Despite advances in medical knowledge, parasitic diseases remain a significant global health burden and their pharmacological treatment is often hampered by drug toxicity. Therefore, drug delivery systems may provide useful advantages when used in combination with conventional therapeutic compounds. Dendrimers are three-dimensional polymeric structures, characterized by a central core, branches and terminal functional groups. These nanostructures are known for their defined structure, great water solubility, biocompatibility and high encapsulation ability against a wide range of molecules. Furthermore, the high ratio between terminal groups and molecular volume render them a hopeful vector for drug delivery. These nanostructures offer several advantages compared to conventional drugs for the treatment of parasitic infection. Dendrimers deliver drugs to target sites with reduced dosage, solving side effects that occur with accepted marketed drugs. In recent years, extensive progress has been made towards the use of dendrimers for therapeutic, prophylactic and diagnostic purposes for the management of parasitic infections. The present review highlights the potential of several dendrimers in the management of parasitic diseases.

scholarly journals SMILES-Based Deep Generative Scaffold Decorator for De-Novo Drug Design

2020 ◽  
Author(s):  
Josep Arús-Pous ◽  
Atanas Patronov ◽  
Esben Jannik Bjerrum ◽  
Christian Tyrchan ◽  
Jean-Louis Reymond ◽  
...  
Keyword(s):  
Data Augmentation ◽  
De Novo ◽  
Chemical Space ◽  
Generative Models ◽  
Synthetic Chemistry ◽  
Specific Knowledge ◽  
De Novo Drug Design ◽  
Wide Range ◽  
Small Set ◽  
Synthetic Approaches

Molecular generative models trained with small sets of molecules represented as SMILES strings are able to generate large regions of the chemical space. Unfortunately, due to the sequential nature of SMILES strings, these models are not able to generate molecules given a scaffold (i.e. partially-built molecules with explicit attachment points). Herein we report a new SMILES-based molecular generative architecture that generates molecules from scaffolds and can be trained from any arbitrary molecular set. This is possible thanks to a new molecular set pre-processing algorithm that exhaustively cuts all combinations of acyclic bonds of every molecule, obtaining a large number of scaffold-decorations combinations. Moreover, it serves as a data augmentation technique and can be readily coupled with randomized SMILES to obtain even better results with small sets. Two examples showcasing the potential of the architecture in medicinal and synthetic chemistry are described: First, models were trained with a training set obtained from a small set of Dopamine Receptor D2 (DRD2) active modulators and were able to meaningfully decorate a wide range of scaffolds and obtain molecular series predicted active on DRD2. Second, a larger set of drug-like molecules from ChEMBL was selectively sliced using synthetic chemistry constraints (RECAP rules). Moreover, the resulting scaffold-decorations were filtered to only allow decorations that were fragment-like. This allowed models trained with this dataset to selectively decorate diverse scaffolds with fragments that were generally predicted to be synthesizable and attachable to the scaffold using known synthetic approaches. In both cases, the models were already able to decorate molecules using specific knowledge without the need to add it with other techniques, such as reinforcement learning. We envision that this architecture will become a useful addition to the already existent architectures for de-novo molecular generation.

scholarly journals Robust and continuous oil/water separation with superhydrophobic glass microfiber membrane by vertical polymerization under harsh conditions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Seeun Woo ◽  
Hong Ryul Park ◽  
Jinyoung Park ◽  
Johan Yi ◽  
Woonbong Hwang
Keyword(s):  
Low Cost ◽  
Three Dimensional ◽  
High Water ◽  
Alkaline Solutions ◽  
Oxygen Plasma Treatment ◽  
Membrane Thickness ◽  
Water Separation ◽  
Wide Range ◽  
Oil Water Separation ◽  
Oil Water

AbstractWe report a robust and continuous oil/water separation with nanostructured glass microfiber (GMF) membranes modified by oxygen plasma treatment and self-assembled monolayer coating with vertical polymerization. The modified GMF membrane had a nanostructured surface and showed excellent superhydrophobicity. With an appropriate membrane thickness, a high water intrusion pressure (< 62.7 kPa) was achieved for continuous pressure-driven separation of oil/water mixtures with high flux (< 4418 L h−1 m−2) and high oil purity (> 99%). Under simulated industrial conditions, the modified GMF membrane exhibited robust chemical stability against strong acidic/alkaline solutions and corrosive environments. The proposed superhydrophobic composite coating technique is simple, low cost, environmentally friendly, and suitable for the mass production of scalable three-dimensional surfaces. Moreover, its stability and customizable functionality offers considerable potential for a wide range of novel applications.

scholarly journals Aqueous dispersions of oligomer-grafted carbon nanomaterials with controlled surface charge and minimal framework damage

2014 ◽  
Vol 173 ◽  
pp. 273-285 ◽  
Author(s):  
Sheng Hu ◽  
Shu Chen ◽  
Robert Menzel ◽  
Angela D. Goode ◽  
Mary P. Ryan ◽  
...  
Keyword(s):  
Surface Charge ◽  
Carbon Nanomaterials ◽  
Water Solubility ◽  
Thermochemical Treatment ◽  
High Water ◽  
Ionic Character ◽  
Gravimetric Analysis ◽  
Physiochemical Properties ◽  
Toxicological Effects ◽  
Wide Range

Functionalised carbon nanomaterials (CNMs), with an undamaged carbon framework and controlled physiochemical properties, are desirable for a wide range of scientific studies and commercial applications. The use of a thermochemical grafting approach provides a versatile means to functionalise both multi-walled carbon nanotubes (MWCNTs) and carbon black (CB) nanoparticles without altering their inherent structures. The functionalisation process was investigated by employing various types of grafting monomers; to improve water solubility, reagents were chosen that introduced an ionic character either intrinsically or after further chemical reactions. The degree of grafting for both MWCNTs and CB ranged from 3–27 wt%, as established by thermal gravimetric analysis (TGA). Raman spectroscopy confirmed that the structural framework of the MWCNTs was unaffected by the thermochemical treatment. The effectiveness of the surface modification was demonstrated by significantly improved dispersibility and stability in water, and further quantified by zeta-potential analysis. The concentration of stable, individualised and grafted MWCNTs in water ranged from ∼30 to 80 μg mL−1after centrifugation at 10 000 g for 15 min, whereas functionalised CB in water showed improved dispersibility up to ∼460 μg mL−1. The successful preparation of structurally identical but differently functionalised nanoparticle panels, with high water compatibility and minimal framework damage, is useful for controlled experiments. For example, they can be used to explore the relationship between toxicological effects and specific physiochemical properties, such as surface charge and geometry.

scholarly journals Drug Repurposing Approach Targeted Against Main Protease of SARS-CoV-2 Exploiting ‘Neighbourhood Behaviour’ in 3D Protein Structural Space and 2D Chemical Space of Small Molecules

2020 ◽  
Author(s):  
Sohini Chakraborti ◽  
Narayanaswamy Srinivasan
Keyword(s):  
Small Molecules ◽  
Chemical Space ◽  
Three Dimensional ◽  
International Health ◽  
Drug Repurposing ◽  
Self Medication ◽  
Drug Candidates ◽  
Main Protease ◽  
Structural Space ◽  
Prior Approval

<p>The current global crisis due to COVID-19 has almost brought normal life to standstill in most parts of the world. With our research interest on repurposing known drugs/drug candidates targeting various diseases, we decided to analyse the available data on the deadly pathogen that has already taken thousands of lives since its outbreak in China in December 2019. Our host institute is now shutdown and we are confining ourselves to our homes with limited access to computational resources. Using a simple <i>in silico</i> approach based on the principle of ‘neighbourhood behaviour’ in three-dimensional (3D) space and two-dimensional (2D) space of protein and small molecules respectively, we have identified potential drugs/drug candidates which can be repurposed against protein targets encoded by the SARS-CoV-2 genome. Based on our preliminary analysis, we have so far prioritized more than 20 known drugs/drug candidates which might elucidate anti-coronavirus properties by binding to main protease of the pathogen. These drugs belong to diverse therapeutic areas such as antiviral, anticancer, antibacterial agents etc. Notably, apart from many synthetic molecules, our analysis also hints that phytochemicals obtained from vinca plant (vinca alkaloids) and camptotheca tree (camptothecin and its derivatives) have the potential to bind to main protease of SARS-CoV-2. In-depth investigation on our findings are currently on-going. Here we are presenting the results we obtained so far. The sole purpose of making these preliminary findings openly available to the community is for the experimental biologists and biomedical researchers to investigate our predictions in experimental set ups and for the clinicians to evaluate the potential of these findings for anti-COVID-19 treatment. <b>Our findings should only be used for research purposes and we strongly urge that no individual should interpret these findings for any self-diagnosis or self-medication without the prior approval from competent international health/medical regulatory agencies.</b></p>

scholarly journals SMILES-Based Deep Generative Scaffold Decorator for De-Novo Drug Design

2020 ◽  
Author(s):  
Josep Arús-Pous ◽  
Atanas Patronov ◽  
Esben Jannik Bjerrum ◽  
Christian Tyrchan ◽  
Jean-Louis Reymond ◽  
...  
Keyword(s):  
Data Augmentation ◽  
De Novo ◽  
Chemical Space ◽  
Generative Models ◽  
Synthetic Chemistry ◽  
Specific Knowledge ◽  
De Novo Drug Design ◽  
Wide Range ◽  
Small Set ◽  
Synthetic Approaches

Molecular generative models trained with small sets of molecules represented as SMILES strings are able to generate large regions of the chemical space. Unfortunately, due to the sequential nature of SMILES strings, these models are not able to generate molecules given a scaffold (i.e. partially-built molecules with explicit attachment points). Herein we report a new SMILES-based molecular generative architecture that generates molecules from scaffolds and can be trained from any arbitrary molecular set. This is possible thanks to a new molecular set pre-processing algorithm that exhaustively cuts all combinations of acyclic bonds of every molecule, obtaining a large number of scaffold-decorations combinations. Moreover, it serves as a data augmentation technique and can be readily coupled with randomized SMILES to obtain even better results with small sets. Two examples showcasing the potential of the architecture in medicinal and synthetic chemistry are described: First, models were trained with a training set obtained from a small set of Dopamine Receptor D2 (DRD2) active modulators and were able to meaningfully decorate a wide range of scaffolds and obtain molecular series predicted active on DRD2. Second, a larger set of drug-like molecules from ChEMBL was selectively sliced using synthetic chemistry constraints (RECAP rules). Moreover, the resulting scaffold-decorations were filtered to only allow decorations that were fragment-like. This allowed models trained with this dataset to selectively decorate diverse scaffolds with fragments that were generally predicted to be synthesizable and attachable to the scaffold using known synthetic approaches. In both cases, the models were already able to decorate molecules using specific knowledge without the need to add it with other techniques, such as reinforcement learning. We envision that this architecture will become a useful addition to the already existent architectures for de-novo molecular generation.

scholarly journals Hydrogels for the Delivery of Plant-Derived (Poly)Phenols

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3254
Author(s):  
Nicola Micale ◽  
Andrea Citarella ◽  
Maria Sofia Molonia ◽  
Antonio Speciale ◽  
Francesco Cimino ◽  
...  
Keyword(s):  
Water Solubility ◽  
Biological Fluids ◽  
Three Dimensional ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Polymeric Networks ◽  
Wide Range ◽  
Swelling Capacity ◽  
Polymeric Component ◽  
External Stimuli

This review deals with hydrogels as soft and biocompatible vehicles for the delivery of plant-derived (poly)phenols, compounds with low general toxicity and an extraordinary and partially unexplored wide range of biological properties, whose use presents some major issues due to their poor bioavailability and water solubility. Hydrogels are composed of polymeric networks which are able to absorb large amounts of water or biological fluids while retaining their three-dimensional structure. Apart from this primary swelling capacity, hydrogels may be easily tailored in their properties according to the chemical structure of the polymeric component in order to obtain smart delivery systems that can be responsive to various internal/external stimuli. The functionalization of the polymeric component of hydrogels may also be widely exploited to facilitate the incorporation of bioactive compounds with different physicochemical properties into the system. Several prototype hydrogel systems have been designed for effective polyphenol delivery and potential employment in the treatment of human diseases. Therefore, the inherent features of hydrogels have been the focus of considerable research efforts over the past few decades. Herein, we review the most recent advances in (poly)phenol-loaded hydrogels by analyzing them primarily from the therapeutic perspective and highlighting the innovative aspects in terms of design and chemistry.

scholarly journals Design principles and biological applications of red-emissive two-photon carbon dots

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Pooria Lesani ◽  
Aina Hazeera Mohamad Hadi ◽  
Zufu Lu ◽  
Stefano Palomba ◽  
Elizabeth J. New ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Near Infrared ◽  
Water Solubility ◽  
High Water ◽  
Photon Absorption ◽  
Biological Applications ◽  
Two Photon Absorption ◽  
Two Photon ◽  
Current State ◽  
Wide Range

AbstractCarbon dots have been gaining attention in the field of nanobiotechnology due to their superior photostability, high water solubility, ease of synthesis and surface functionalization, chemical inertness, low toxicity, and excellent biocompatibility. They also exhibit good two-photon absorption and unique tunable optical properties across a wide range of wavelengths, from ultraviolet to near infrared endowing them with potential for a variety of biological applications. Recently, there has been a growing interest in the synthesis and development of red-emissive two-photon carbon dots. Here we present recent progress in the design requirements for red-emissive two-photon carbon dots, and review current state-of-the-art systems, covering their applications in bioimaging, biosensing, and photothermal and photodynamic therapy.

Recent Advances in Efficacy of Using Doxorubicin Gold Nanoparticles for Chemo-, Radio-, Photothermal, and Photodynamic therapy

2021 ◽  
Vol 18 ◽  
Author(s):  
Niloufar Choubdar ◽  
Sara Avizheh ◽  
Seyed Ali Karimifard
Keyword(s):  
Gold Nanoparticles ◽  
Photodynamic Therapy ◽  
Side Effects ◽  
Water Solubility ◽  
High Water ◽  
Multi Drug Resistance ◽  
Therapeutic Drug ◽  
Target Cells ◽  
Recent Advances ◽  
Effective Cancer Therapy

: Nanoparticles (NPs) have been widely used in drug delivery systems specifically for chemo-, radio-, photothermal, and photodynamic therapy. Due to the lack of selectivity toward tumor cells the main target in therapies is to deliver drugs to cancer cells to reduce side effects. Gold nanoparticles (AuNPs) have been described as “promising nanocarriers for therapeutics” due to many properties such as low inherent toxicity, high water solubility and biocompatibility. Many research groups have focused on taking advantage of two or more therapies simultaneously to have increased efficacy using a lower dosage of the therapeutic drug and reduced multi drug resistance (MDR). Alternatively, doxorubicin (Dox) modification has been used as a strategy for increased selectivity toward target cells. Over the years, many studies have been performed on NPs to eliminate side effects using polymers, peptides, proteins, DNA, metallic NPs, microgels, and hydrogels on drug carrierse. In this review, recent advances of using Dox-AuNPs for chemo-, radio-, photothermal, photodynamic and combination therapy are briefly discussed, and we highlight recent progression in the application of Dox-AuNPs for effective cancer therapy.

General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

2018 ◽  
Author(s):  
Marc Montesinos-Magraner ◽  
Matteo Costantini ◽  
Rodrigo Ramirez-Contreras ◽  
Michael E. Muratore ◽  
Magnus J. Johansson ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Chemical Space ◽  
Synthetic Approach ◽  
Asymmetric Cyclopropanation ◽  
Redox Active ◽  
Wide Range ◽  
Leaving Group ◽  
Stereoelectronic Properties ◽  
Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

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