394 results match your criteria cycloaddition allowed


Heterohelicenes through 1,3-Dipolar Cycloaddition of Sydnones with Arynes: Synthesis, Origins of Selectivity, and Application to pH-Triggered Chiroptical Switch with CPL Sign Reversal.

JACS Au 2021 Jun 14;1(6):807-818. Epub 2021 May 14.

Université Paris-Saclay, CEA, Service de Chimie Bio-organique et de Marquage, DMTS, Gif-sur-Yvette 91191, France.

Regioselective access to heterohelicenes through the 1,3-dipolar cycloaddition of sydnones with arynes is described. Novel access to sydnones and poly(hetero)aromatic aryne precursors allowed the introduction of chemical diversity over multiple positions of the helical scaffolds. The origins of the unconventional regioselectivity during the cycloaddition steps was systematically investigated using density functional theory (DFT) calculations, unveiling the key features that control this reactivity, namely, face-to-face (π···π) or edge-to-face (C-H···π) interactions, primary orbital interactions and distortion from coplanarity in the transition structures (TSs) of the transformation. Read More

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Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition.

J Org Chem 2021 Aug 24. Epub 2021 Aug 24.

Enamine Ltd.; Chervonotkatska 78, 02094 Kyiv, Ukraine, www.enamine.net.

A general approach to bicyclic fused pyrrolidines via [3 + 2]-cycloaddition between nonstabilized azomethyne ylide and endocyclic electron-deficient alkenes was elaborated. "Push-pull" alkenes and CF-alkenes did not react with the azomethyne ylide under the previously reported conditions, and we developed a superior protocol (LiF, 140 °C, no solvent). Among obtained products were medchem-relevant bicyclic sulfones, monofluoro-, difluoro-, and trifluoromethyl-substituted pyrrolidines. Read More

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Controlled density glycodendron microarrays for studying carbohydrate-lectin interactions.

Org Biomol Chem 2021 Sep 13;19(34):7357-7362. Epub 2021 Aug 13.

Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Av. Américo Vespucio 49, 41092 Seville, Spain.

Glycodendron microarrays with defined valency have been constructed by on-chip synthesis on hydrophobic indium tin oxide (ITO) coated glass slides and employed in lectin-carbohydrate binding studies with several plant and human lectins. Glycodendrons presenting sugar epitopes at different valencies were prepared by spotwise strain-promoted azide-alkyne cycloaddition (SPAAC) between immobilised cyclooctyne dendrons and azide functionalised glycans. The non-covalent immobilisation of dendrons on the ITO surface by hydrophobic interaction allowed us to study dendron surface density and SPAAC conversion rate by in situ MALDI-TOF MS analysis. Read More

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September 2021

Effect of Novel Deep Eutectic Solvents on the Endo/Exo Ratio of Diels-Alder Reactions at Room Temperature.

ACS Omega 2021 Aug 22;6(30):19392-19399. Epub 2021 Jul 22.

Department of Chemistry-DBA Center, University of Lleida, ETSEA, Av. Rovira Roure 191, 25198 Lleida, Catalonia, Spain.

The Diels-Alder reaction is a prototypical example of a thermally allowed [4 + 2] cycloaddition with good control over the regio- and stereochemical outcomes. Therefore, Diels-Alder reactions in which adjacent stereocenters are generated at the two ends of the newly formed single bonds imply two different possible stereochemical outcomes. In cases where the dienophile has a single electron-withdrawing substituent, the outcome can often be predicted by applying the known "endo rule". Read More

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Design, synthesis, and pharmacological activity of new pyrrolo[1,2-a]pyrazine translocator protein (tspo) ligands.

Med Chem 2021 Aug 5. Epub 2021 Aug 5.

FSBI Zakusov Research Institute of Pharmacology, Baltiyskaya 8, Moscow, 125315. Russian Federation.

Background: Translocator protein 18 kDa (TSPO) is a promising target for the creation of effective and safe neuropsychotropic drugs. The ligands of TSPO exhibit anxiolytic, antidepressant, neuroprotective and other activities without the side effects of benzodiazepines.

Methods: New TSPO ligands in the series of N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamides derivatives were designed using calculated pharmacophore model and molecular docking analysis. Read More

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Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform.

Int J Mol Sci 2021 Jun 17;22(12). Epub 2021 Jun 17.

Department of Pharmacy and CIRPEB, University of Naples "Federico II", Via Montesano 49, 80131 Naples, Italy.

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol-ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Read More

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Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents-The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s).

Molecules 2021 Jun 14;26(12). Epub 2021 Jun 14.

Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Leninskii pr., 31, 119991 Moscow, Russia.

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine -nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Read More

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Small-Molecule Investigation of Diels-Alder Complexes for Thermoreversible Crosslinking in Polymeric Applications.

J Org Chem 2021 Jul 21;86(13):8933-8944. Epub 2021 Jun 21.

Joint Research Network on Advanced Materials and Systems (JONAS), Freiburg Materials Research Center, University of Freiburg, Stefan-Meier-Str. 21, D-79104 Freiburg, Germany.

Combinations of dienes and dienophiles were examined in order to elicit possible combinations for thermoreversible crosslinking units. Comparison of experimental results and quantum calculations indicated that reaction kinetics and activation energy were much better prediction factors than change in enthalpy for the prediction of successful cycloaddition. Further testing on diene-dienophile pairs that underwent successful cycloaddition determined the feasibility of thermoreversibility/retro-reaction of each of the Diels-Alder compounds. Read More

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One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives.

Chem Asian J 2021 Aug 12;16(16):2286-2297. Epub 2021 Jul 12.

Institute of Chemistry, Saint Petersburg State University, Universitetsky prospect 26, Saint Petersburg, 198504, Russia.

Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC -H O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95-99% deuteration degree was synthesized for the first time. Read More

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"Clicking" fragment leads to novel dual-binding cholinesterase inhibitors.

Bioorg Med Chem 2021 Jul 7;42:116269. Epub 2021 Jun 7.

National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland; National Centre for Nuclear Research, 05-400 Otwock-Świerk, Poland.

Cholinesterase inhibitors are potent therapeutics in the treatment of Alzheimer's disease. Among them, dual binding ligands have recently gained a lot of attention. We discovered novel dual-binding cholinesterase inhibitors, using "clickable" fragments, which bind to either catalytic active site (CAS) or peripheral anionic site (PAS) of the enzyme. Read More

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Merging Imidazolidines with a Trifluoromethylated Tetrasubstituted Carbon through Tungsten Catalyzed 1,3-Dipolar Cycloaddition.

J Org Chem 2021 Jun 19;86(11):7714-7724. Epub 2021 May 19.

Institute of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, 475004, People's Republic of China.

An unprecedented 1,3-dipole cycloaddition between acyclic CF-ketimines and -benzyl azomethine ylide has been allowed by tungsten catalysis, furnishing a range of novel imidazolidines bearing a trifluoromethylated tetrasubstituted carbon center. This reaction appears as one of rare examples that challenging acyclic CF-ketimines have been engaged in 1,3-cycloaddition reactions. The capability for gram-scale synthesis and variant derivatizations of cycloaddition adducts illustrates the synthetic potential of this approach. Read More

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A Protecting-Group-Free Synthesis of (-)-Salvinorin A.

Chemistry 2021 May 2;27(29):7968-7973. Epub 2021 May 2.

Fakultät Chemie und Lebensmittelchemie, Organische Chemie I, Technische Universität Dresden, Bergstraße 66, 01069, Dresden, Germany.

A concise enantioselective total synthesis of the neoclerodane diterpene (-)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels-Alder reactions were applied to generate the tricyclic core. Read More

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Interfacial Photo-Cross-Linking: Simple but Powerful Approach for Fabricating Capsule Polymer Particles with Tunable pH-Responsive Controlled Release Capability.

ACS Appl Mater Interfaces 2021 Mar 22;13(8):10359-10375. Epub 2021 Feb 22.

Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.

Herein, we describe capsule polymer particles with precisely controlled pH-responsive release properties prepared directly via the interfacial photo-cross-linking of spherical poly(2-diethylaminoethyl methacrylate--2-cinnamoylethyl methacrylate) (P(DEAEMA-CEMA)) particles. In the interfacial photo-cross-linking, photoreactive cinnamoyl groups in the polymer particles were cross-linked via [2π + 2π] cycloaddition reactions at the polymer/water interface, showing that the shell-cross-linked hollow polymer particles can be directly prepared from spherical polymer particles. The approach has fascinating advantages such as using minimal components, simplicity, and not requiring sacrificial template particles and toxic solvents. Read More

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New Methods and Strategies in the Synthesis of Terpenoid Natural Products.

Acc Chem Res 2021 03 17;54(6):1347-1359. Epub 2021 Feb 17.

Department of Chemistry, University of California, Irvine, California 92697-2025, United States.

Indoloterpenoids of the paxilline type belong to a large family of secondary metabolites that exhibit unique molecular architectures and a diverse set of biological activities. More than 100 congeners identified to date share a common structural motif that contains an indole moiety fused to a rearranged diterpenoid fragment. The representative physiological and cellular effects attributed to this family of natural products include neurological and insecticidal activities, modulation of lipid balance, and inhibition of mitosis. Read More

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Robust anti-infective multilayer coatings with rapid self-healing property.

Mater Sci Eng C Mater Biol Appl 2021 Feb 2;121:111828. Epub 2021 Jan 2.

School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia; Centre for Materials Science, Queensland University of Technology, Brisbane, Queensland 4000, Australia. Electronic address:

Surface coatings are extensively applied on biomedical devices to provide protection against biofouling and infections. However, most surface coatings prevent both bacteria and cells interactions with the biomaterials, limiting their uses as implants. Furthermore, damage to the surface such as scratches and abrasions can happen during transport and clinical usage, resulting in the loss of antibacterial property. Read More

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February 2021

Biosynthetic Functionalization of Nonribosomal Peptides.

J Am Chem Soc 2021 02 11;143(7):2736-2740. Epub 2021 Feb 11.

Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland.

Nonribosomal peptides (NRPs) are a therapeutically important class of secondary metabolites that are produced by modular synthetases in assembly-line fashion. We previously showed that a single Trp-to-Ser mutation in the initial Phe-loading adenylation domain of tyrocidine synthetase completely switches the specificity toward clickable analogues. Here we report that this minimally invasive strategy enables efficient functionalization of the bioactive NRP on the pathway level. Read More

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February 2021

Quest for an Efficient 2-in-1 MOF-Based Catalytic System for Cycloaddition of CO to Epoxides under Mild Conditions.

ACS Appl Mater Interfaces 2021 Feb 9;13(7):8344-8352. Epub 2021 Feb 9.

Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie, 50-383 Wrocław, Poland.

We have devised a straightforward tandem postsynthetic modification strategy for Zr-based metal-organic framework (MOF) materials, which resulted in a series of well-defined 2-in-1 heterogeneous catalysts, -, exhibiting high catalytic activity in the synthesis of cyclic carbonates under solvent-free and co-catalyst-free conditions. The materials feature precisely located co-catalyst moieties decorating the metal nodes throughout the bulk of the MOF and yield cyclic carbonates with up to 99% efficiency at room temperature. We use diffuse reflectance infrared Fourier transform (DRIFT) and solid-state nuclear magnetic resonance (NMR) measurements to elucidate the role of each component in this model catalytic reaction. Read More

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February 2021

Discovery and Surprises with Cyclizations, Cycloadditions, Fragmentations, and Rearrangements in Complex Settings.

Acc Chem Res 2021 02 3;54(4):890-902. Epub 2021 Feb 3.

Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland.

We discuss a number of synthesis routes to complex natural products recently reported from our group. Although the structures are quite varied, we demonstrate the research endeavor as a setting to examine the implementation of cyclizations, cycloadditions, rearrangements, and fragmentations. We showcase how the various transformations enabled access to key core structures and thereby allowed the rapid introduction of complexity. Read More

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February 2021

Annulative Methods in the Synthesis of Complex Meroterpene Natural Products.

Acc Chem Res 2021 02 15;54(3):583-594. Epub 2021 Jan 15.

Department of Chemistry, University of California-Berkeley, 826 Latimer Hall, Berkeley, California 94720, United States.

From the venerable Robinson annulation to the irreplaceable Diels-Alder cycloaddition, annulation reactions have fueled the progression of the field of natural product synthesis throughout the past century. In broader terms, the ability to form a cyclic molecule directly from two or more simpler fragments has transformed virtually every aspect of the chemical sciences from the synthesis of organic materials to bioconjugation chemistry and drug discovery. In this Account, we describe the evolution of our meroterpene synthetic program over the past five years, enabled largely by the development of a tailored anionic annulation process for the synthesis of hydroxylated 1,3-cyclohexanediones from lithium enolates and the reactive β-lactone-containing feedstock chemical diketene. Read More

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February 2021

Structural Diversity of Peptoids: Tube-Like Structures of Macrocycles.

Molecules 2020 Dec 31;26(1). Epub 2020 Dec 31.

Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.

Peptoids, or poly--substituted glycines, are characterised by broad structural diversity. Compared to peptides, they are less restricted in rotation and lack backbone-derived H bonding. Nevertheless, certain side chains force the peptoid backbone into distinct conformations. Read More

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December 2020

Synthesis of Three-Dimensionally Fascinating Diterpenoid Alkaloids and Related Diterpenes.

Acc Chem Res 2021 01 22;54(1):22-34. Epub 2020 Dec 22.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug, and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Three-dimensional cage-like natural products represent astounding and long-term challenges in the research endeavors of total synthesis. A central issue that synthetic chemists need to address lies in how to efficiently construct the polycyclic frameworks as well as to install the requisite substituent groups. The diterpenoid alkaloids that biogenetically originate from amination of diterpenes and diversify through late-stage skeletal reorganization belong to such a natural product category. Read More

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January 2021

Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs.

Molecules 2020 Nov 30;25(23). Epub 2020 Nov 30.

Institute of Clinical Trials, West China Hospital, Sichuan University, Chengdu 610041, China.

Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. Read More

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November 2020

Thermodynamically Stable o-Quinodimethane: Synthesis, Structure, and Reactivity.

Chemistry 2021 Feb 1;27(11):3665-3669. Epub 2020 Dec 1.

Department of Applied Chemistry for Environment, Kwansei Gakuin University, 2-1 Gakuen, Sanda, 669-1337, Japan.

Thermal isomerization of cyclobutaphenanthrene to o-quinodimethane was investigated. Sterically congested substituents or electron-donating substituents on the four-membered ring promoted the ring-opening, affording o-quinodimethane in a relatively stable form. Isolation of the newly prepared o-quinodimethane allowed its structural elucidation and investigation of its potential reactivities. Read More

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February 2021

An optimal "Click" formulation strategy for antibody-drug conjugate synthesis.

Bioorg Med Chem 2020 12 6;28(24):115808. Epub 2020 Oct 6.

The Texas A&M Drug Discovery Laboratory, Department of Chemistry, Texas A&M University, College Station, TX 77843, United States; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA; Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA. Electronic address:

As a versatile reaction for bioconjugation, Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) has enormous potential in the synthesis of antibody-drug conjugates (ADCs). In order to optimize CuAAC-based ADC synthesis, we characterized kinetically different formulation processes by mimicking ADC synthesis using small molecules and subsequently revealed unique kinetic behaviors of different combinations of alkyne and azide conditions. Our results indicate that under ADC synthesis conditions, for an alkyne-containing drug, its concentration has minimal impact on the reaction rate when an antibody has a non-metal-chelating azide but is proportional to concentration when an antibody contains a metal-chelating azide; however, for an alkyne-containing antibody, the ADC synthesis rate is proportional to the concentration of a drug with a non-metal-chelating azide but displays almost no dependence on drug concentration with a metal-chelating azide. Read More

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December 2020

Conversion of CO into Chloropropene Carbonate Catalyzed by Iron (II) Phthalocyanine Hypercrosslinked Porous Organic Polymer.

Molecules 2020 Oct 9;25(20). Epub 2020 Oct 9.

Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), c/Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain.

Commercial iron (II) phthalocyanine (FePc) was knitted with biphenyl using a Friedel-Crafts reaction to yield a micro-meso porous organic polymer (FePc-POP) with a specific surface area of 427 m/g and 5.42% of iron loading. This strategy allowed for the direct synthesis of a heterogeneous catalyst from an iron containing monomer. Read More

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October 2020

[Site-selective and Stereoselective Syntheses Controlled by the Electron-withdrawing Properties of Cationic Heterocycles].

Yakugaku Zasshi 2020 ;140(10):1225-1233

Faculty of Pharmacy, Meijo University.

This article describes our stereoselective and site-selective chemical methods for exploiting cationic heterocycles as electron-withdrawing groups (EWGs). We envisioned that the phosphoramide N-H proton of a pyridyl phosphoramide 3 would be activated by the cationic pyridinium moiety that is formed upon protonation. The resulting imide-like N-H proton and the acidic pyridinium proton of the pyridinium phosphoramide 3⋅HX cooperate together, making 3⋅HX a highly acidic dual Brønsted acid. Read More

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October 2020

New water-soluble derivatives of chitin and their based nanoparticles: Antibacterial and catalytic activity.

Int J Biol Macromol 2020 Nov 22;163:2005-2012. Epub 2020 Sep 22.

Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, Russian Federation; Zelinsky Institute of Organic Chemistry RAS, Leninsky Prosp. 47, Moscow 119991, Russian Federation.

A facile route towards new chitin derivatives with both catalytical and biological activities is proposed in the course of methodology development aimed at the design of polyfunctional materials on the basis of renewable and accessible natural polysaccharides. Ultrasound-promoted and Cu(I)-catalyzed azido-alkyne click cycloaddition of the propargylic ester of nicotinic acid and its N-methylated analogue to the azido chitin derivative allowed us to obtain previously unknown non-toxic water-soluble derivatives of chitin. The obtained polymers and their based nanoparticles demonstrated a high antibacterial activity in vitro, which is comparable or even superior to that of commercial antibiotics ampicillin and gentamicin. Read More

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November 2020

Enantiospecific Generation and Trapping Reactions of Aryne Atropisomers.

J Am Chem Soc 2020 Oct 28;142(40):16921-16925. Epub 2020 Sep 28.

Aix Marseille Univ, CNRS, Centrale Marseille, ISM2, 13397 Marseille, France.

Enantioenriched aryne atropisomers having a biaryl stereogenic axis vicinal to the reactive triple bond are demonstrated to exist. These reaction intermediates are easily produced in situ and can undergo the standard aryne cycloaddition chemistry in an enantiospecific manner. Notably, the aryne atropisomers herein have allowed the practical syntheses of a small nanographene as well as some triptycene and anthracene derivatives that embed stereogenic axes of controlled absolute configurations. Read More

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October 2020

Total Synthesis of Liangshanone.

Angew Chem Int Ed Engl 2020 12 15;59(52):23609-23614. Epub 2020 Oct 15.

Key Laboratory of Drug Targeting and Drug Delivery Systems of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drugs and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

The first total synthesis of liangshanone, a hexacyclic ent-kaurane diterpenoid alkaloid, has been completed. Its intricate cagelike framework was assembled through several key transformations, including an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence, a tandem alkene cleavage/Mannich cyclization, a Robinson-type annulation, and an intramolecular aldol reaction. Notably, an organocatalytic enantioselective α-hydroxymethylation process allowed the preparation of an enantiomerically enriched tricyclic intermediate that should enable asymmetric access to the target natural product. Read More

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December 2020

Synthesis of the Novel AT Receptor Tracer [F]Fluoropyridine-Candesartan via Click Chemistry.

ACS Omega 2020 Aug 3;5(32):20353-20362. Epub 2020 Aug 3.

Centre de Recherche du CHUM, 900 rue Saint-Denis, Montréal, Québec H2X 0A9, Canada.

A novel 7-((4-(3-((2-[F]fluoropyridin-3-yl)oxy)propyl)-1-1,2,3-triazol-1-yl)methyl)-1-benzo[]imidazole derivative of the angiotensin II type-1 receptor (ATR) blocker candesartan, [F]fluoropyridine-candesartan, was synthesized via the copper-catalyzed azide-alkyne cycloaddition click reaction between 2-[F]fluoro-3-(pent-4-yn-1-yloxy)pyridine ([F]FPyKYNE) and the tetrazole-protected azido-candesartan derivative, followed by acid deprotection. This three-step, two-pot, and two-step purification synthesis was done within 2 h. The use of tris[(1-hydroxypropyl-1-1,2,3-triazol-4-yl)methyl]amine (THPTA) as a Cu(I) stabilizing agent increased the overall radiochemical yield by 4-fold (10 ± 2%, = 13) compared to the reaction without THPTA (2. Read More

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