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Search for "antimalarial" in Full Text gives 125 result(s) in Beilstein Journal of Organic Chemistry.
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- . Tacrine (1) is an acridine derivative used in the treatment of Alzheimer’s disease. A plethora of acridine derivatives have been synthesized and clinically proved with various biological activities such as ethacridine (antibacterial drug; 2), acranil (antiviral drug; 3) and quinacrine (antimalarial agent
- further studied for their antimicrobial, antituberculosis and antimalarial effects. Scheme 41 demonstrates the mechanism involving a direct Claisen–Schmidt condensation to intermediate A followed by a sequential [3 + 3] cycloaddition with 104 yields B. Finally, dehydration and hydrogen removal from B
- , antiulcer, anxiolytic, antiherpes agents [115][116][117][118][119]. Similarly, pyrazolo-pyridines are found to be potent antibacterial (131), cytotoxic (132), antiproliferative (133) and antimalarial (134) agents (Figure 10) [120][121]. 8.2.1 Imidazo[1,2-a]pyridine: Sun and co-workers [122] accomplished the
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B
- Takashi Nishiyama,
- Erina Hamada,
- Daishi Ishii,
- Yuuto Kihara,
- Nanase Choshi,
- Natsumi Nakanishi,
- Mari Murakami,
- Kimiko Taninaka,
- Noriyuki Hatae and
- Tominari Choshi
Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62
- 1). These pyrrolo[2,3-c]quinolines have been demonstrated to show antimalarial and antibacterial biological activities [2][3][4]. Thus, the development of a convenient and efficient synthetic route to the pyrrolo[2,3-c]quinoline skeleton has attracted considerable attention from organic and
Graphical Abstract
Figure 1: Natural products possessing the pyrrolo[2,3-c]quinoline skeleton.
Scheme 1: Total synthesis of marinoquinolines and the failure of the introduction of a tetrahydroquinoline mo...
Scheme 2: Retrosynthetic analysis of the pyrrolo[2,3-c]quinoline ring construction.
Scheme 3: Synthesis of N-substituted 4-aminopyrrolo[3,2-c]quinoline 18.
Scheme 4: Synthesis of the tetrahydroquinoline moiety through cycloamination.
Scheme 5: Synthesis of trigonoine B (1).
The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst
- Deniz Tözendemir and
- Cihangir Tanyeli
Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43
- outshined by sulfonamides in medicinal chemistry, they have a large array of biologic activities that show promising effects as potent anti-HIV-1 [34], anti-hepatitis C [35], antifungal [36], insecticidal/acaricial [37] and antimalarial [38] agents. Results and Discussion We have previously reported the
Graphical Abstract
Scheme 1: Synthesis of organocatalyst 5.
Figure 1: Structures of the screened organocatalysts.
Scheme 2: Proposed transition state for the SMA of 1-thionaphthol to trans-chalcones.
Figure 2: Comparison of the ee values of SMA in the presence of THF and DCM as solvent.
Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines
- Geetanjali S. Sontakke,
- Rahul K. Shukla and
- Chandra M. R. Volla
Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42
- natural products [1][2][3][4], agrochemicals and pharmaceuticals having potent biological activities, such as antimalarial, antibacterial and anticancer activities [5][6][7][8][9][10][11]. Due to their wide range of applications, selective functionalization of quinolines at various positions has gained
Graphical Abstract
Figure 1: Bioactive molecules containing the 2-aminoquinoline motif.
Scheme 1: C2-selective C–N bond formation of N-oxides.
Scheme 2: Substrate scope of N-sulfonyl-1,2,3-triazoles. Reaction conditions: 1a (0.2 mmol), 2 (0.24 mmol) an...
Scheme 3: Substrate scope of quinoline N-oxides. Reaction conditions: 1 (0.2 mmol), 2a (0.24 mmol) and DCE (2...
Scheme 4: Late-stage modification of natural products.
Scheme 5: Substrate scope for the reaction of substituted triazoles with isoquinoline N-oxide.
Scheme 6: Gram-scale and one-pot synthesis.
Scheme 7: Proposed mechanism.
Synthetic strategies of phosphonodepsipeptides
- Jiaxi Xu
Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41
- are derivatives of the new antimalarial drug fosmidomycin and inhibited the 1-deoxy-ᴅ-xylulose 5-phosphate reductoisomerase. The phosphonodepsipeptides 194 were synthesized as prodrugs with an increased activity after oral administration due to a chemical modification of the phosphonate moiety. For
Graphical Abstract
Figure 1: Phosphonopeptides, phosphonodepsipeptides, peptides, and depsipeptides.
Figure 2: The diverse strategies for phosphonodepsipeptide synthesis.
Scheme 1: Synthesis of α-phosphonodepsidipeptides as inhibitors of leucine aminopeptidase.
Figure 3: Structure of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16).
Scheme 2: Synthesis of α-phosphonodepsidipeptide 17 as coupling partner for cyclen-containing phosphonodepsip...
Scheme 3: Synthesis of α-phosphonodepsidipeptides containing enantiopure hydroxy ester as VanX inhibitors.
Scheme 4: Synthesis of α-phosphonodepsidipeptides as VanX inhibitors.
Scheme 5: Synthesis of optically active α-phosphonodepsidipeptides as VanX inhibitors.
Scheme 6: The synthesis of phosphonodepsipeptides through a thionyl chloride-catalyzed esterification of N-Cb...
Scheme 7: Synthesis of α-phosphinodipeptidamide as a hapten.
Scheme 8: Synthesis of α-phosphonodepsioctapeptide 41.
Scheme 9: Synthesis of phosphonodepsipeptides via an in situ-generated phosphonochloridate.
Scheme 10: Synthesis of α-phosphonodepsitetrapeptides 58 as inhibitors of the aspartic peptidase pepsin.
Scheme 11: Synthesis of a β-phosphonodepsidipeptide library 64.
Scheme 12: Synthesis of another β-phosphonodepsidipeptide library.
Scheme 13: Synthesis of γ-phosphonodepsidipeptides.
Scheme 14: Synthesis of phosphonodepsipeptides 85 as folylpolyglutamate synthetase inhibitors.
Scheme 15: Synthesis of the γ-phosphonodepsitripeptide 95 as an inhibitor of γ-gutamyl transpeptidase.
Scheme 16: Synthesis of phosphonodepsipeptides as inhibitors and probes of γ-glutamyl transpeptidase.
Scheme 17: Synthesis of phosphonyl depsipeptides 108 via DCC-mediated condensation and oxidation.
Scheme 18: Synthesis of phosphonodepsipeptides 111 with BOP and PyBOP as coupling reagents.
Scheme 19: Synthesis of optically active phosphonodepsipeptides with BOP and PyBOP as coupling reagents.
Scheme 20: Synthesis of phosphonodepsipeptides with BroP and TPyCIU as coupling reagents.
Scheme 21: Synthesis of a phosphonodepsipeptide hapten with BOP as coupling reagent.
Scheme 22: Synthesis of phosphonodepsitripeptide with BOP as coupling reagent.
Scheme 23: Synthesis of norleucine-derived phosphonodepsipeptides 135 and 138.
Scheme 24: Synthesis of norleucine-derived phosphonodepsipeptides 141 and 144.
Scheme 25: Solid-phase synthesis of phosphonodepsipeptides.
Scheme 26: Synthesis of phosphonodepsidipeptides via the Mitsunobu reaction.
Scheme 27: Synthesis of γ-phosphonodepsipeptide via the Mitsunobu reaction.
Scheme 28: Synthesis of phosphonodepsipeptides via a multicomponent condensation reaction.
Scheme 29: Synthesis of phosphonodepsipeptides with a functionalized side-chain via a multicomponent condensat...
Scheme 30: High yielding synthesis of phosphonodepsipeptides via a multicomponent condensation.
Scheme 31: Synthesis of optically active phosphonodepsipeptides via a multicomponent condensation reaction.
Scheme 32: Synthesis of N-phosphoryl phosphonodepsipeptides.
Scheme 33: Synthesis of phosphonodepsipeptides via the alkylation of phosphonic monoesters.
Scheme 34: Synthesis of phosphonodepsipeptides as inhibitors of aspartic protease penicillopepsin.
Scheme 35: Synthesis of phosphonodepsipeptides as prodrugs.
Scheme 36: Synthesis of phosphonodepsithioxopeptides 198.
Scheme 37: Synthesis of phosphonodepsipeptides.
Scheme 38: Synthesis of phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acid.
Scheme 39: Synthesis of phosphonodepsipeptides with C-1-hydroxyalkylphosphonate via the rhodium-catalyzed carb...
Scheme 40: Synthesis of phosphonodepsipeptides with a C-1-hydroxyalkylphosphonate motif via a copper-catalyzed...
Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors
- Emine Kayahan,
- Mathias Jacobs,
- Leen Braeken,
- Leen C.J. Thomassen,
- Simon Kuhn,
- Tom van Gerven and
- M. Enis Leblebici
Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202
- indigo carmine, diclofenac, and benzoylecgonine. The reactor volume was 0.15 mL [36]. The PSTY of the photodegradation of indigo carmine was calculated as 0.01 mol·day−1·kW−1 (Table 1, entry 8). In another study, those microcapillary films were used to synthesize ascaridole, an antimalarial drug, from α
Graphical Abstract
Figure 1: The momentum transport affects the mass transfer and the light field. All transport phenomena need ...
Figure 2: Common photomicroreactor designs: (a) Straight channel, (b) serpentine channel, (c) square serpenti...
Figure 3: Benchmarked photoreactors: (a) Microcapillaries in parallel, (b) microcapillaries in series, (c) fl...
Figure 4: Photochemical reactions that are detailed in Table 1.
Figure 5: Structured reactors designed for enhancing the mass transfer: (a) Packed bed photoreactor, (b) mono...
Figure 6: Comparison of the LED board designs of photomicroreactors: (a) CC array design, (b) MC array design...
Figure 7: Illustration of the light scattering phenomenon inside a photocatalytic flow reactor.
Figure 8: Efficiency of the absorption process in scattering situations with respect to pure absorption situa...
Figure 9: Different types of distributors: (a) Traditional or consecutive manifold, (b) bifurcation unit dist...
Et3N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties
- Dharmender Singh,
- Vipin Kumar and
- Virender Singh
Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146
- products [1][2][3][4] and pharmacologically active compounds endowed with anticancer [5][6][7][8][9], anti-inflammatory, antioxidant, antimalarial, antifungal, and antileishmanial activities (Figure 1) [10][11][12][13]. Notably, this privileged scaffold is incorporated in several marketed drugs such as
Graphical Abstract
Figure 1: Representative examples of some commercial drugs and biologically active alkaloids.
Scheme 1: Synthesis of β-carboline-linked 2-nitrochalcones.
Scheme 2: Synthesis of β-carboline-linked benzothiophenone frameworks.
Scheme 3: Comparison of outcome of one-pot vs two-pot approach.
Scheme 4: One-pot synthesis of β-carboline C-1-tethered benzothiophenone derivatives.
Scheme 5: One-pot synthesis of β-carboline C-3-linked benzothiophenone derivatives.
Scheme 6: One-pot synthesis of β-carboline-linked benzothiophene derivative 6C.
Scheme 7: Control experiment in the presence of a radical scavenger.
Figure 2: Proposed reaction mechanism.
Figure 3: Fluorescence spectra of 2aA–nA, 2bB, 2hB, and 6C.
Figure 4: Fluorescence spectra of 4aA–gA, and 4eB.
Heterogeneous photocatalysis in flow chemical reactors
- Christopher G. Thomson,
- Ai-Lan Lee and
- Filipe Vilela
Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125
Graphical Abstract
Figure 1: A) Bar chart of the publications per year for the topics “Photocatalysis” (49,662 instances) and “P...
Figure 2: A) Professor Giacomo Ciamician and Dr. Paolo Silber on their roof laboratory at the University of B...
Scheme 1: PRC trifluoromethylation of N-methylpyrrole (1) using hazardous gaseous CF3I safely in a flow react...
Figure 3: A) Unit cells of the three most common crystal structures of TiO2: rutile, brookite, and anatase. R...
Figure 4: Illustration of the key semiconductor photocatalysis events: 1) A photon with a frequency exceeding...
Figure 5: Photocatalytic splitting of water by oxygen vacancies on a TiO2(110) surface. Reprinted with permis...
Figure 6: Proposed adsorption modes of A) benzene, B) chlorobenzene, C) toluene, D) phenol, E) anisole, and F...
Figure 7: Structures of the sulfonate-containing organic dyes RB5 (3) and MX-5B (4) and the adsorption isothe...
Figure 8: Idealised triclinic unit cell of a g-C3N4 type polymer, displaying possible hopping transport scena...
Figure 9: Idealised structure of a perfect g-C3N4 sheet. The central unit highlighted in red represents one t...
Figure 10: Timeline of the key processes of charge transport following the photoexcitation of g-C3N4, leading ...
Scheme 2: Photocatalytic bifunctionalisation of heteroarenes using mpg-C3N4, with the selected examples 5 and ...
Figure 11: A) Structure of four linear conjugated polymer photocatalysts for hydrogen evolution, displaying th...
Figure 12: Graphical representation of the common methods used to immobilise molecular photocatalysts (PC) ont...
Figure 13: Wireless light emitter-supported TiO2 (TiO2@WLE) HPCat spheres powered by resonant inductive coupli...
Figure 14: Graphical representation of zinc–perylene diimide (Zn-PDI) supramolecular assembly photocatalysis v...
Scheme 3: Upconversion of NIR photons to the UV frequency by NaYF4:Yb,Tm nanocrystals sequentially coated wit...
Figure 15: Types of reactors employed in heterogeneous photocatalysis in flow. A) Fixed bed reactors and the s...
Figure 16: Electrochemical potential of common semiconductor, transition metal, and organic dye-based photocat...
Scheme 4: Possible mechanisms of an immobilised molecular photoredox catalyst by oxidative or reductive quenc...
Scheme 5: Scheme of the CMB-C3N4 photocatalytic decarboxylative fluorination of aryloxyacetic acids, with the...
Scheme 6: Scheme of the g-C3N4 photocatalytic desilylative coupling reaction in flow and proposed mechanism [208].
Scheme 7: Proposed mechanism of the radical cyclisation of unsaturated alkyl 2-bromo-1,3-dicarbonyl compounds...
Scheme 8: N-alkylation of benzylamine and schematic of the TiO2-coated microfluidic device [213].
Scheme 9: Proposed mechanism of the Pt@TiO2 photocatalytic deaminitive cyclisation of ʟ-lysine (23) to ʟ-pipe...
Scheme 10: A) Proposed mechanism for the photocatalytic oxidation of phenylboronic acid (24). B) Photos and SE...
Scheme 11: Proposed mechanism for the DA-CMP3 photocatalytic aza-Henry reaction performed in a continuous flow...
Scheme 12: Proposed mechanism for the formation of the cyclic product 32 by TiO2-NC HPCats in a slurry flow re...
Scheme 13: Reaction scheme for the photocatalytic synthesis of homo and hetero disulfides in flow and scope of...
Scheme 14: Reaction scheme for the MoOx/TiO2 HPCat oxidation of cyclohexane (34) to benzene. The graph shows t...
Scheme 15: Proposed mechanism of the TiO2 HPC heteroarene C–H functionalisation via aryl radicals generated fr...
Scheme 16: Scheme of the oxidative coupling of benzylamines with the HOTT-HATN HPCat and selected examples of ...
Scheme 17: Photocatalysis oxidation of benzyl alcohol (40) to benzaldehyde (41) in a microflow reactor coated ...
Figure 17: Mechanisms of Dexter and Forster energy transfer.
Scheme 18: Continuous flow process for the isomerisation of alkenes with an ionic liquid-immobilised photocata...
Scheme 19: Singlet oxygen synthetic step in the total synthesis of canataxpropellane [265].
Scheme 20: Scheme and proposed mechanism of the singlet oxygen photosensitisation by CMP_X HPCats, with the st...
Scheme 21: Structures of CMP HPCat materials applied by Vilela and co-workers for the singlet oxygen photosens...
Scheme 22: Polyvinylchloride resin-supported TDCPP photosensitisers applied for singlet oxygen photosensitisat...
Scheme 23: Structure of the ionically immobilised TPP photosensitiser on amberlyst-15 ion exchange resins (TPP...
Scheme 24: Photosensitised singlet oxygen oxidation of citronellol (46) in scCO2, with automatic phase separat...
Scheme 25: Schematic of PS-Est-BDP-Cl2 being applied for singlet oxygen photosensitisation in flow. A) Pseudo-...
Scheme 26: Reaction scheme of the singlet oxygen oxidation of furoic acid (54) using a 3D-printed microfluidic...
Figure 18: A) Photocatalytic bactericidal mechanism by ROS oxidative cleavage of membrane lipids (R = H, amino...
Figure 19: A) Suggested mechanisms for the aqueous pollutant degradation by TiO2 in a slurry flow reactor [284-287]. B)...
Figure 20: Schematic of the flow system used for the degradation of aqueous oxytetracycline (56) solutions [215]. M...
Scheme 27: Degradation of a salicylic acid (57) solution by a coupled solar photoelectro-Fenton (SPEF) process...
Figure 21: A) Schematic flow diagram using the TiO2-coated NETmix microfluidic device for an efficient mass tr...
Anthelmintic drug discovery: target identification, screening methods and the role of open science
- Frederick A. Partridge,
- Ruth Forman,
- Carole J. R. Bataille,
- Graham M. Wynne,
- Marina Nick,
- Angela J. Russell,
- Kathryn J. Else and
- David B. Sattelle
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- arylpyrrole antimalarial series [82]. We are not aware of a similar real-time, fully open source effort being applied to anthelmintic discovery, but this would be an exciting prospect for the field. However, researchers have been freely releasing open tools useful for drug discovery, openly describing their
- to radically open up the drug development process, with the goal of increasing the efficiency, reducing the cost of research duplication, reducing the hoarding of data and creating collaborative communities [174]. This approach has been applied to the discovery of compounds with antimalarial activity
Graphical Abstract
Figure 1: Structures of some current front-line anthelmintics discussed in this review. *Denotes the stereoge...
Figure 2: Structures of new anthelmintics drugs developed through repurposing, and new drugs or drug candidat...
Figure 3: Compounds with anthelmintic activity identified by a combination of screening against Ancylostoma c...
Figure 4: Inhibitors of S. mansoni thioredoxin glutathione reductase with anthelmintic activity [140].
Figure 5: Active compounds from anthelmintic screens using the MMV Pathogen Box. NTS: newly transformed schis...
Figure 6: Two resolution approaches to enantiopure PZQ (R)-5 discovered through A) open science and B) contra...
Synthesis and properties of quinazoline-based versatile exciplex-forming compounds
- Rasa Keruckiene,
- Simona Vekteryte,
- Ervinas Urbonas,
- Matas Guzauskas,
- Eigirdas Skuodis,
- Dmytro Volyniuk and
- Juozas V. Grazulevicius
Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101
- , such as monitoring of specific biological activities and as antimalarial and anticancer agents [5][6]. However, electroactive properties of derivatives of this acceptor have been scarcely reported. Quinazoline-based compounds were used as hosts for red phosphorescent OLEDs with an external quantum
Graphical Abstract
Scheme 1: Synthesis of quinazoline derivatives 1–3. Conditions: i) ammonium acetate, copper(II) chloride, iso...
Figure 1: DSC (a, b, c) and TGA (d) curves of compounds 1–3. Scan rates were 20 °C/min (TGA) and 10 °C/min (D...
Figure 2: Frontier-orbital distributions and optimized geometries at the ground state of quinazoline-based co...
Figure 3: Cyclic voltammograms of quinazoline-based compounds 1–3.
Figure 4: UV–vis absorption spectra of compounds 1–3. a) Theoretical and b) experimental spectra of compounds ...
Figure 5: Fluorescence spectra (a) of dilute solutions and thin films of compounds 1–3 (λexc = 350 nm and PL ...
Figure 6: Electron and hole NTOs of compounds 1–3 in the S1 excited state (vacuum).
Figure 7: Chemical structures of exciplex-forming materials used, and visualization of white electroluminesce...
Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches
- Rodrigo Costa e Silva,
- Luely Oliveira da Silva,
- Aloisio de Andrade Bartolomeu,
- Timothy John Brocksom and
- Kleber Thiago de Oliveira
Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83
- group publication [74] on new antimalarial drugs can be highlighted (Scheme 29). The authors report a 3.4 gram-scale preparation of ascaridole, in this case a synthetic intermediate, using TPP as photocatalyst. Another example of a scaled-up endoperoxide approach involves the stereoselective singlet
- -flow with O2). One very relevant example of a photooxygenation protocol is the Seeberger group’s semi-synthesis of the antimalarial API artemisinin (Scheme 32) [79]. They have established a gram-scale continuous protocol with a photooxygenation promoted by TPP starting from dihydroartemisinic acid
- oxygen and their mechanisms. Adapted from [67]. First scaled up ascaridole preparation from α-terpinene. Antimalarial drug synthesis using an endoperoxidation approach. Photooxygenation of colchicine. Synthesis of (−)-pinocarvone from abundant (+)-α-pinene. Seeberger’s semi-synthesis of artemisinin
Graphical Abstract
Figure 1: Chemical structures of the porphyrinoids and their absorption spectra: in bold are highlighted the ...
Figure 2: Photophysical and photochemical processes (Por = porphyrin). Adapted from [12,18].
Figure 3: Main dual photocatalysts and their oxidative/reductive excited state potentials, including porphyri...
Scheme 1: Photoredox alkylation of aldehydes with diazo acetates using porphyrins and a Ru complex. aUsing a ...
Scheme 2: Proposed mechanism for the alkylation of aldehydes with diazo acetates in the presence of TPP.
Scheme 3: Arylation of heteroarenes with aryldiazonium salts using TPFPP as photocatalyst, and corresponding ...
Scheme 4: A) Scope with different aryldiazonium salts and enol acetates. B) Photocatalytic cycles and compari...
Scheme 5: Photoarylation of isopropenyl acetate A) Comparison between batch and continuous-flow approaches an...
Scheme 6: Dehalogenation induced by red light using thiaporphyrin (STPP).
Scheme 7: Applications of NiTPP as both photoreductant and photooxidant.
Scheme 8: Proposed mechanism for obtaining tetrahydroquinolines by reductive quenching.
Scheme 9: Selenylation and thiolation of anilines.
Scheme 10: NiTPP as photoredox catalyst in oxidative and reductive quenching, in comparison with other photoca...
Scheme 11: C–O bond cleavage of 1-phenylethanol using a cobalt porphyrin (CoTMPP) under visible light.
Scheme 12: Hydration of terminal alkynes by RhIII(TSPP) under visible light irradiation.
Scheme 13: Regioselective photocatalytic hydro-defluorination of perfluoroarenes by RhIII(TSPP).
Scheme 14: Formation of 2-methyl-2,3-dihydrobenzofuran by intramolecular hydro-functionalization of allylpheno...
Scheme 15: Photocatalytic oxidative hydroxylation of arylboronic acids using UNLPF-12 as heterogeneous photoca...
Scheme 16: Photocatalytic oxidative hydroxylation of arylboronic acids using MOF-525 as heterogeneous photocat...
Scheme 17: Preparation of the heterogeneous photocatalyst CNH.
Scheme 18: Photoinduced sulfonation of alkenes with sulfinic acid using CNH as photocatalyst.
Scheme 19: Sulfonic acid scope of the sulfonation reactions.
Scheme 20: Regioselective sulfonation reaction of arimistane.
Scheme 21: Synthesis of quinazolin-4-(3H)-ones.
Scheme 22: Selective photooxidation of aromatic benzyl alcohols to benzaldehydes using Pt/PCN-224(Zn).
Scheme 23: Photooxidation of benzaldehydes to benzoic acids using Pt or Pd porphyrins.
Scheme 24: Photocatalytic reduction of various nitroaromatics using a Ni-MOF.
Scheme 25: Photoinduced cycloadditions of CO2 with epoxides by MOF1.
Figure 4: Electronic configurations of the species of oxygen. Adapted from [66].
Scheme 26: TPP-photocatalyzed generation of 1O2 and its application in organic synthesis. Adapted from [67-69].
Scheme 27: Pericyclic reactions involving singlet oxygen and their mechanisms. Adapted from [67].
Scheme 28: First scaled up ascaridole preparation from α-terpinene.
Scheme 29: Antimalarial drug synthesis using an endoperoxidation approach.
Scheme 30: Photooxygenation of colchicine.
Scheme 31: Synthesis of (−)-pinocarvone from abundant (+)-α-pinene.
Scheme 32: Seeberger’s semi-synthesis of artemisinin.
Scheme 33: Synthesis of artemisinin using TPP and supercritical CO2.
Scheme 34: Synthesis of artemisinin using chlorophyll a.
Scheme 35: Quercitol stereoisomer preparation.
Scheme 36: Photocatalyzed preparation of naphthoquinones.
Scheme 37: Continuous endoperoxidation of conjugated dienes and subsequent rearrangements leading to oxidized ...
Scheme 38: The Opatz group total synthesis of (–)-oxycodone.
Scheme 39: Biomimetic syntheses of rhodonoids A, B, E, and F.
Scheme 40: α-Photooxygenation of chiral aldehydes.
Scheme 41: Asymmetric photooxidation of indanone β-keto esters by singlet oxygen using PTC as a chiral inducer...
Scheme 42: Asymmetric photooxidation of both β-keto esters and β-keto amides by singlet oxygen using PTC-2 as ...
Scheme 43: Bifunctional photo-organocatalyst used for the asymmetric oxidation of β-keto esters and β-keto ami...
Scheme 44: Mechanism of singlet oxygen oxidation of sulfides to sulfoxides.
Scheme 45: Controlled oxidation of sulfides to sulfoxides using protonated porphyrins as photocatalysts. aIsol...
Scheme 46: Photochemical oxidation of sulfides to sulfoxides using PdTPFPP as photocatalyst.
Scheme 47: Controlled oxidation of sulfides to sulfoxides using SnPor@PAF as a photosensitizer.
Scheme 48: Syntheses of 2D-PdPor-COF and 3D-Pd-COF.
Scheme 49: Photocatalytic oxidation of A) thioanisole to methyl phenyl sulfoxide and B) various aryl sulfides,...
Scheme 50: General mechanism for oxidation of amines to imines.
Scheme 51: Oxidation of secondary amines to imines.
Scheme 52: Oxidation of secondary amines using Pd-TPFPP as photocatalyst.
Scheme 53: Oxidative amine coupling using UNLPF-12 as heterogeneous photocatalyst.
Scheme 54: Synthesis of Por-COF-1 and Por-COF-2.
Scheme 55: Photocatalytic oxidation of amines to imines by Por-COF-2.
Scheme 56: Photocyanation of primary amines.
Scheme 57: Synthesis of ᴅ,ʟ-tert-leucine hydrochloride.
Scheme 58: Photocyanation of catharanthine and 16-O-acetylvindoline using TPP.
Scheme 59: Photochemical α-functionalization of N-aryltetrahydroisoquinolines using Pd-TPFPP as photocatalyst.
Scheme 60: Ugi-type reaction with 1,2,3,4-tetrahydroisoquinoline using molecular oxygen and TPP.
Scheme 61: Ugi-type reaction with dibenzylamines using molecular oxygen and TPP.
Scheme 62: Mannich-type reaction of tertiary amines using PdTPFPP as photocatalyst.
Scheme 63: Oxidative Mannich reaction using UNLPF-12 as heterogeneous photocatalyst.
Scheme 64: Transformation of amines to α-cyanoepoxides and the proposed mechanism.
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- dihydroartemisinic acid (DHAA) [64][65]. Also, high efficient and recyclable catalytic systems based on metal-organic frameworks (MOFs) have also been reported for the tandem hemisynthesis of artemisinin [66]. In a remarkable work, this antimalarial drug was obtained by a new route involving enyne metathesis as the
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Opening up connectivity between documents, structures and bioactivity
- Christopher Southan
Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54
- (i.e., entombment) makes the ARC in result tables more difficult to extract. A specific example of the problem can be given for a 2017 article on new antimalarial compounds entering development [8]. Because the chemistry representations were restricted only to images in the PDF a blog post was
Graphical Abstract
Figure 1: A schematic of the document > assay > result > compound > protein target relationships, D-A-R-C-P [...
Figure 2: PMID content with totals appended to each segment. Those for ChEMBL were downloaded from European P...
Figure 3: Chemistry content comparison for the three sources with totals appended to each segment, selected a...
Figure 4: Target comparisons with totals in each segment. These were downloaded as UniProt ID lists selected ...
Figure 5: Connectivity for PMID 31339551. The lead structures from the paper, LUF7224 was curated by GtoPdb a...
Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica
- Soleiman E. Helaly,
- Wilawan Kuephadungphan,
- Patima Phainuphong,
- Mahmoud A. A. Ibrahim,
- Kanoksri Tasanathai,
- Suchada Mongkolsamrit,
- Janet Jennifer Luangsa-ard,
- Souwalak Phongpaichit,
- Vatcharin Rukachaisirikul and
- Marc Stadler
Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293
- possess nonselective activities in biological systems and exhibit antimicrobial [28], cytotoxic [29], antimycobacterial [30], and antimalarial [31] effects. Pigmentosin A (1) and its new derivative pigmentosin B (2) exhibited weak activity against B. subtilis, with MIC values of 12.5 and 100 μg/mL
Graphical Abstract
Figure 1: Chemical structures of the isolated compounds 1–6.
Figure 2: Experimental and TDDFT-calculated ECD spectra of compounds 1 (A), 2 (B), and 3 (C) in MeOH.
Figure 3: A) Selected COSY (bold bonds) and HMBC (red arrows) correlations for compounds 2 and 3. B) Partial ...
Figure 4: Chemical structures of selected, literature-known compounds that are related to this study.
Figure 5: HPLC–UV–vis profiles (200–600 nm) generated from the culture filtrate extracts of several isolates ...
Figure 6: HPLC–UV–vis profiles (200–600 nm) generated from the culture filtrate extracts of several isolates ...
Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering
- Eric J. N. Helfrich,
- Geng-Min Lin,
- Christopher A. Voigt and
- Jon Clardy
Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283
- restricted members possess significant biological activities, like the anticancer agent taxol (1) [4] or the antimalarial agent artemisinin (2, Figure 1) [5][6]. The structural diversity and functional utility of this class of specialized metabolites have combined to encourage efforts to apply the tools of
Graphical Abstract
Figure 1: Examples of bioactive terpenoids.
Figure 2: Repetitive electrophilic and nucleophilic functionalities in terpene and type II PKS-derived polyke...
Figure 3: Abundance and distribution of bacterial terpene biosynthetic gene clusters as determined by genome ...
Figure 4: Terpenoid biosynthesis. Terpenoid biosynthesis is divided into two phases, 1) terpene scaffold gene...
Figure 5: Mechanisms for type I, type II, and type II/type I tandem terpene cyclases. a) Tail-to-head class I...
Figure 6: Functional TC characterization. a) Different terpenes were produced when hedycaryol (18) synthase a...
Figure 7: Selected examples of terpene modification by bacterial CYPs. a) Hydroxylation [89]. b) Carboxylation, h...
Figure 8: Off-target effects observed during heterologous expression of terpenoid BGCs. Unexpected oxidation ...
Figure 9: TC promiscuity and engineering. a) Spata-13,17-diene (39) synthase (SpS) can take C15 and C25 oligo...
Figure 10: Substrate promiscuity and engineering of CYPs. a) Selected examples from using a CYP library to oxi...
Figure 11: Engineering of terpenoid pathways. a) Metabolic network of terpenoid biosynthesis. Toxic intermedia...
Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids
- Gerardo M. Ojeda,
- Prabhat Ranjan,
- Pavel Fedoseev,
- Lisandra Amable,
- Upendra K. Sharma,
- Daniel G. Rivera and
- Erik V. Van der Eycken
Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237
- variety of pharmacological and antimicrobial properties [5][6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Figure 1). A key feature of the tetrazole ring is its bioisosteric character with the carboxylic acid and amide functional groups
Graphical Abstract
Figure 1: Bioactive molecules containing a tetrazole, pyridone or isoquinolone ring.
Scheme 1: Approaches for the synthesis of tetrazoles and isoquinolones and their interplay as designed in thi...
Scheme 2: Scope of the Ugi-azide-4CR/deprotection/acylation sequence. Ugi-azide-4CR conducted at the 2.0 mmol...
Scheme 3: Influence of substituents R and R2 on the reaction outcome. For compounds 4k–m the overall yield in...
Scheme 4: Influence of the alkyne and R1 substituent on the reaction outcome.
Scheme 5: Scope of acrylic, heterocyclic and ring-fused N-acylaminomethyl tetrazole substrates.
Scheme 6: Proposed reaction mechanism using substrates 1a and 3a.
Current understanding and biotechnological application of the bacterial diterpene synthase CotB2
- Ronja Driller,
- Daniel Garbe,
- Norbert Mehlmer,
- Monika Fuchs,
- Keren Raz,
- Dan Thomas Major,
- Thomas Brück and
- Bernhard Loll
Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228
- [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial
- inexpensive carbon sources. Prominent examples of optimized terpene production pathways in E. coli are taxadiene, a precursor of the anticancer drug taxol [28], amorpha‐4,11‐diene, an antimalarial drug precursor [29], and cyclooctatin [30]. The scope of this review encompasses a detailed consideration of the
Graphical Abstract
Figure 1: CotB1 synthesizes geranylgeranyl diphosphate (GGDP) 3 from the substrates dimethylallyl diphosphate...
Figure 2: The bacterial diterpene synthase CotB2wt·Mg2+3·F-Dola in the closed, active conformation (PDB-ID 6G...
Figure 3: Conformational changes of CotB2 upon ligand binding. Superposition of CotB2’s open (teal), pre-cata...
Figure 4: View into the active site of CotB2wt·Mg2+3·F-Dola [37] superimposed with CotB2wt·Mg2+B·GGSDP [36]. (A) The ...
Figure 5: View into the active site of CotB2wt·Mg2+3·F-Dola [37]. Identical view as in Figure 4. (A) The bound F-Dola rea...
Figure 6: The WXXXXXRY motif in protein sequences of diterpene TPS from different bacteria. Highlighted is th...
Scheme 1: Overview of the altered product portfolio as a result of introduced point mutations in the active s...
Scheme 2: Catalytic mechanism of CotB2, derived from isotope labeling experiments [34,35], density functional theory...
Figure 7: (A) The inner surface of the active site is shown in gray. The bound F-Dola reaction intermediate i...
Scheme 3: Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons,...
Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids
- Melodi Demiray,
- David J. Miller and
- Rudolf K. Allemann
Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215
- engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with
Graphical Abstract
Scheme 1: Mechanism of the ADS-catalysed conversion of FDP (2) to amorpha-4,11-diene (3), a biosynthetic prec...
Scheme 2: Synthesis of 8-methoxy-FDP (11) and 12-methoxy-FDP (12) (for full synthesis details see Supporting Information File 1).
Figure 1: Total-ion chromatogram of the pentane extractable products formed in an incubation of ADS with 8-me...
Figure 2: 1H NMR spectrum (500 MHz, CDCl3) of the 8-methoxy-γ-humulene (20) generated by ADS from 8-methoxy-F...
Scheme 3: Potential mechanisms for the ADS-catalysed conversion of 8-methoxy-FDP (11) to 8-methoxy-γ-humulene...
Figure 3: Total-ion chromatogram of the pentane extractable products formed in an incubation of ADS with 12-m...
Figure 4: 1H NMR spectrum (400 MHz, CDCl3) of 12-methoxy-β-sesquiphellandrene (26) and 12-methoxyzingiberene (...
Scheme 4: Possible mechanisms for the ADS-catalysed conversion of 12-methoxy-FDP (12) to 12-methoxy-β-sesquip...
An overview of the cycloaddition chemistry of fulvenes and emerging applications
- Ellen Swan,
- Kirsten Platts and
- Anton Blencowe
Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209
- length of the extended pentafulvene chain, and the role of the fulvene in the reaction (diene or dienophile) [127]. In these examples, kigelinol and neoamphilectane are of great interest in biomimetic and natural product chemistry, as they exhibit antitrypanosomal [128][129] and antimalarial [130
Graphical Abstract
Figure 1: General structure of fulvenes, named according to the number of carbon atoms in their ring. Whilst ...
Figure 2: Generic structures of commonly referenced heteropentafulvenes, named according to the heteroatom su...
Scheme 1: Resonance structures of (a) pentafulvene and (b) heptafulvene showing neutral (1 and 2), dipolar (1a...
Scheme 2: Resonance structures of (a) pentafulvenes and (b) heptafulvenes showing the influence of EDG and EW...
Scheme 3: Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the mult...
Scheme 4: Photosensitized oxygenation of 8-cyanoheptafulvene with singlet state oxygen to afford 1,4-epidioxi...
Figure 3: A representation of HOMO–LUMO orbitals of pentafulvene and the influence of EWG and EDG substituent...
Scheme 5: Reactions of (a) 6,6-dimethylpentafulvene participating as 2π and 4π components in cycloadditions w...
Scheme 6: Proposed mechanism for the [6 + 4] cycloaddition of tropone with dimethylfulvene via an ambimodal [...
Scheme 7: Triafulvene dimerization through the proposed 'head-to-tail' mechanism. The dipolar transition stat...
Scheme 8: Dimerization of pentafulvenes via a Diels–Alder cycloaddition pathway whereby one fulvene acts as a...
Scheme 9: Dimerization of pentafulvenes via frustrated Lewis pair chemistry as reported by Mömming et al. [116].
Scheme 10: Simplified reaction scheme for the formation of kempane from an extended-chain pentafulvene [127].
Scheme 11: The enantioselective (>99% ee), asymmetric, catalytic, intramolecular [6 + 2] cycloaddition of fulv...
Scheme 12: Intramolecular [8 + 6] cycloaddition of the heptafulvene-pentafulvene derivative [22,27].
Scheme 13: Reaction scheme for (a) [2 + 2] cycloaddition of 1,2-diphenylmethylenecyclopropene and 1-diethylami...
Scheme 14: Diels–Alder cycloaddition of pentafulvenes derivatives participating as dienes with (i) maleimide d...
Scheme 15: Generic schemes showing pentafulvenes participating as dienophiles in Diels–Alder cycloadditions wi...
Scheme 16: Reaction of 8,8-dicyanoheptafulvene and styrene derivatives to afford [8 + 2] and [4 + 2] cycloaddu...
Scheme 17: Reaction of 6-aminofulvene and maleic anhydride, showing observed [6 + 2] cycloaddition; the [4 + 2...
Scheme 18: Schemes for Diels–Alder cycloadditions in dynamic combinatorial chemistry reported by Boul et al. R...
Scheme 19: Polymerisation and dynamer formation via Diels–Alder cycloaddition between fulvene groups in polyet...
Scheme 20: Preparation of hydrogels via Diels–Alder cycloaddition with fulvene-conjugated dextran and dichloro...
Scheme 21: Ring-opening metathesis polymerisation of norbornene derivatives derived from fulvenes and maleimid...
Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica
- Silvie Rimpelová,
- Michal Jurášek,
- Lucie Peterková,
- Jiří Bejček,
- Vojtěch Spiwok,
- Miloš Majdl,
- Michal Jirásko,
- Miloš Buděšínský,
- Juraj Harmatha,
- Eva Kmoníčková,
- Pavel Drašar and
- Tomáš Ruml
Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189
- . Immunobiological properties of compound 1 SLs, natural compounds predominantly isolated from the species Asteraceae and Apiaceae represent a rich source of small molecules with potential pharmacological effects. Indeed, some of them have reached clinical applications as antimalarial (artemisinin; [24]) or
Graphical Abstract
Figure 1: The structure of the sesquiterpene lactones archangelolide (1) and trilobolide (2).
Scheme 1: Reagents and conditions: a) MeOH, TEA, 48 h, yield 32%; b) (i) 5-azidopentanoic acid, DCC, DCM, 90 ...
Figure 2: Intracellular localization of archangelolide-dansyl (5) in human cells from osteosarcoma (U-2 OS). ...
Figure 3: Co-localization of dansylarchangelolide 5 with a marker of endoplasmic reticulum (top row) and with...
Figure 4: Cartoon representation of sarco/endoplasmic reticulum Ca2+ ATPase binding pocket with A, C) archang...
Figure 5: Molecular surface representation of sarco/endoplasmic reticulum Ca2+ ATPase binding pocket with A) ...
Figure 6: Structural formulae of (i) thapsigargin, (ii) trilobolide (2), and (iii) archangelolide (1). Red pa...
Figure 7: Viability of rat peritoneal cells treated with archangelolide (1), dansylarchangelolide 5 and dansy...
Figure 8: NO production in primary rat macrophages. The cells were treated with archangelolide (1) and dansyl...
Figure 9: Evaluation of cytokine TNF-α secretion in rat peritoneal cells. Stimulation of primary cells was in...
Figure 10: Structure of laserolide.
Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction
- Maryna V. Murlykina,
- Oleksandr V. Kolomiets,
- Maryna M. Kornet,
- Yana I. Sakhno,
- Sergey M. Desenko,
- Victoriya V. Dyakonenko,
- Svetlana V. Shishkina,
- Oleksandr A. Brazhko,
- Vladimir I. Musatov,
- Alexander V. Tsygankov,
- Erik V. Van der Eycken and
- Valentyn A. Chebanov
Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126
- discovery. The target products containing a heterocyclic core bound to a peptide-like chain also showed a broad spectrum of biological activity: β-secretase (BACE1) inhibitory activity [15]; inducing apoptosis in colorectal cancer cells [16]; antimalarial activity against a chloroquine (CQ) non-resistant
Graphical Abstract
Scheme 1: An overview of heterocyclic acids used in the Ugi reaction.
Scheme 2: Synthesis of pyrazolopyridine carboxylic acids 4 [45] and 7 [45] in Doebner-type reaction.
Figure 1: Molecular structure of N-(2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-6-(4-methoxyphenyl)-3-...
Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams
- Edorta Martínez de Marigorta,
- Jesús M. de Los Santos,
- Ana M. Ochoa de Retana,
- Javier Vicario and
- Francisco Palacios
Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104
- , that shows antimalarial activity [40] and satavaptan, a selective V2-receptor antagonist that is useful for the treatment of cirrhosis (Figure 5) [41][42]. Additionally, methisazone is a 2-oxindole derivative that has been used as antiviral drug, especially for the prophylactic treatment of small-pox
Graphical Abstract
Figure 1: γ-Lactam-derived structures considered in this review.
Figure 2: Alkaloids containing an isoindolinone moiety.
Figure 3: Alkaloids containing the 2-oxindole ring system.
Figure 4: Drugs and biological active compounds containing an isoindolinone moiety.
Figure 5: Drugs and biologically active compounds bearing a 2-oxindole skeleton.
Scheme 1: Three-component reaction of benzoic acid 1, amides 2 and DMSO (3).
Scheme 2: Copper-catalysed three-component reaction of 2-iodobenzoic acids 10, alkynylcarboxylic acids 11 and...
Scheme 3: Proposed mechanism for the formation of methylene isoindolinones 13.
Scheme 4: Copper-catalysed three-component reaction of 2-iodobenzamide 17, terminal alkyne 18 and pyrrole or ...
Scheme 5: Palladium-catalysed three-component reaction of ethynylbenzamides 21, secondary amines 22 and CO (23...
Scheme 6: Proposed mechanism for the formation of methyleneisoindolinones 24.
Scheme 7: Copper-catalysed three-component reaction of formyl benzoate 29, amines 2 and alkynes 18.
Scheme 8: Copper-catalysed three-component reaction of formylbenzoate 29, amines 2 and ketones 31.
Scheme 9: Non-catalysed (A) and phase-transfer catalysed (B) three-component reactions of formylbenzoic acids ...
Scheme 10: Proposed mechanism for the formation of isoindolinones 36.
Scheme 11: Three-component reaction of formylbenzoic acid 33, amines 2 and fluorinated silyl ethers 39.
Scheme 12: Three-component Ugi reaction of 2-formylbenzoic acid (33), diamines 41 and isocyanides 42.
Scheme 13: Non-catalysed (A, B) and chiral phosphoric acid promoted (C) three-component Ugi reactions of formy...
Scheme 14: Proposed mechanism for the enantioselective formation of isoindolinones 46.
Scheme 15: Three-component reaction of benzoic acids 33 or 54, amines 2 and TMSCN (52).
Scheme 16: Several variations of the three-component reaction of formylbenzoic acids 33, amines 2 and isatoic ...
Scheme 17: Proposed mechanism for the synthesis of isoindoloquinazolinones 57.
Scheme 18: Three-component reaction of isobenzofuranone 61, amines 2 and isatoic anhydrides 56.
Scheme 19: Palladium-catalysed three-component reaction of 2-aminobenzamides 59, 2-bromobenzaldehydes 62 and C...
Scheme 20: Proposed mechanism for the palladium-catalysed synthesis of isoindoloquinazolinones 57.
Scheme 21: Four-component reaction of 2-vinylbenzoic acids 67, aryldioazonium tetrafluoroborates 68, DABCO·(SO2...
Scheme 22: Plausible mechanism for the formation of isoindolinones 71.
Scheme 23: Three-component reaction of trimethylsilylaryltriflates 77, isocyanides 42 and CO2 (78).
Scheme 24: Plausible mechanism for the three-component synthesis of phthalimides 79.
Scheme 25: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, arenes 86 and diaryliodonium...
Scheme 26: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, diaryliodonium salts 87 and ...
Scheme 27: Proposed mechanism for the formation of 2,3-diarylisoindolinones 88, 89 and 92.
Scheme 28: Palladium-catalysed three-component reaction of chloroquinolinecarbaldehydes 97 with isocyanides 42...
Scheme 29: Palladium-catalysed three-component reaction of imines 99 with CO (23) and ortho-iodoarylimines 100....
Scheme 30: Palladium-catalysed three-component reaction of amines 2 with CO (23) and aryl iodide 105.
Scheme 31: Three-component reaction of 2-ethynylanilines 109, perfluoroalkyl iodides 110 and carbon monoxide (...
Scheme 32: Ultraviolet-induced three-component reaction of N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69) an...
Scheme 33: Proposed mechanism for the preparation of oxindoles 115.
Scheme 34: Three-component reaction of acrylamide 113, CO (23) and 1,4-benzodiazepine 121.
Scheme 35: Multicomponent reaction of sulfonylacrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO·(...
Scheme 36: Proposed mechanism for the preparation of oxindoles 124.
Scheme 37: Three-component reaction of N-arylpropiolamides 128, aryl iodides 129 and boronic acids 130.
Scheme 38: Proposed mechanism for the formation of diarylmethylene- and diarylallylideneoxindoles 131 and 132.
Scheme 39: Three-component reaction of cyclohexa-1,3-dione (136), amines 2 and alkyl acetylenedicarboxylates 1...
Scheme 40: Proposed mechanism for the formation of 2-oxindoles 138.
Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin
- Toni Smeilus,
- Farnoush Mousavizadeh,
- Johannes Krieger,
- Xingzhao Tu,
- Marcel Kaiser and
- Athanassios Giannis
Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51
- -hydroxymethyl-9-epi-artemisinin (18), starting from the known and readily available chiral aldehyde 3 and alkyne 4. Subsequently, the synthesized compounds have been evaluated for their antimalarial activity against the drug-sensitive P. falciparum NF54 strain. All of them were inactive. In addition, they did
- of artemisinin (1; qinghaosu, Figure 1) from Artemisia annua L. and the discovery of its antimalarial properties in 1971 represent one of the greatest medical breakthroughs of the 20th century [1][2]. For these achievements Youyou Tu was awarded the Nobel Prize in Physiology or Medicine in 2015 [3
- , whereas the desired (+)-3-hydroxymethylartemisinin (2) was produced from 17 in two steps including epimerization and cleavage of the TES group in excellent yield (Scheme 3). Finally, we evaluated the antimalarial activity of (+)-3-hydroxymethylartemisinin (2) as well as of the derivatives 16 and 18
Graphical Abstract
Figure 1: Structures of the natural (+)-artemisinin (1) and the synthesized (+)-3-hydroxymethylartemisinin (2...
Scheme 1: Synthesis of the Diels–Alder precursor 8 over four steps in 71% yield, starting from aldehyde 3 and...
Scheme 2: Synthesis of (+)-3-hydroxymethyl-9-desmethylartemisinin (16), starting from Diels–Alder derivatives ...
Scheme 3: Synthesis of (+)-3-hydroxymethyl-9-epi-artemisinin (18) and (+)-3-hydroxymethylartemisinin (2). Rea...
Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products
- Stephen M. Geddis,
- Teodora Coroama,
- Suzanne Forrest,
- James T. Hodgkinson,
- Martin Welch and
- David R. Spring
Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245
- -product generated during the synthesis of the antimalarial chloroquine [2]. Given this high potential for the discovery of useful chemical entities, we have recently been engaged in research regarding a family of quinolone natural products which are produced by the actinomycete Pseudonocardia sp. CL38489
Graphical Abstract
Figure 1: A family of quinolone natural products 1–8, which were first isolated from Pseudonocardia sp. CL384...
Scheme 1: Proposed use of the chemistry developed towards the total synthesis of 5 and 6 for generation of na...
Scheme 2: Sonagashira coupling of alkynes 10a and 10b with commercially available acid chloride 9 to give yno...
Scheme 3: Conjugate addition of primary amines 12a–f with ynones 11a and 11b. aFollowing concentration in vac...
Scheme 4: Cyclisation of precursors 13 to natural product analogues 14 using palladium- or copper-catalysed c...
Scheme 5: Use of an excess of DMEDA in the Cu-catalysed cyclisation of 13bb resulted in the generation of 14bg...
Figure 2: Growth of E. coli ESS with time in the presence of 200 μM of each compound. A) Natural product seri...
Figure 3: Growth of S. aureus 25923 with time in the presence of 200 μM of each compound. A) Natural product ...
Figure 4: OD520 (absorption corresponding to pyocyanin) normalised by the culture population (measured by OD6...
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
- Michael K. Bogdos,
- Emmanuel Pinard and
- John A. Murphy
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- nicotinamides to highly functionalised quinolines, such as the antimalarial drug quinine. The ability of this protocol to tolerate such highly functionalised molecules, with such a variety of functional groups present, really justifies the claims of the authors that this protocol is ideal for LSF in drug
Graphical Abstract
Figure 1: Depiction of the energy levels of a typical organic molecule and the photophysical processes it can...
Figure 2: General catalytic cycle of a photocatalyst in a photoredox organocatalysed reaction. [cat] – photoc...
Figure 3: Structures and names of the most common photocatalysts encountered in the reviewed literature.
Figure 4: General example of a reductive quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocata...
Figure 5: General example of an oxidative quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocat...
Scheme 1: Oxidative coupling of aldehydes and amines to amides using acridinium salt photocatalysis.
Figure 6: Biologically active molecules containing a benzamide linkage.
Scheme 2: The photocatalytic reduction of amino acids to produce the corresponding free or protected amines.
Scheme 3: The organocatalysed photoredox base-mediated oxidation of thiols to disulfides.
Scheme 4: C-Terminal modification of peptides and proteins using organophotoredox catalysis.
Scheme 5: The reduction and aryl coupling of aryl halides using a doubly excited photocatalyst (PDI).
Figure 7: Mechanism for the coupling of aryl halides using PDI, which is excited sequentially by two photons.
Scheme 6: The arylation of five-membered heteroarenes using arenediazonium salts under organophotoredox condi...
Scheme 7: The C–H (hetero)arylation of five-membered heterocycles under Eosin Y photocatalysis.
Scheme 8: The C–H sulfurisation of imidazoheterocycles using Eosin B-catalyzed photochemical methods.
Scheme 9: The introduction of the thiocyanate group using Eosin Y photocatalysis.
Scheme 10: Sulfonamidation of pyrroles using oxygen as the terminal oxidant.
Scheme 11: DDQ-catalysed C–H amination of arenes and heteroarenes.
Scheme 12: Photoredox-promoted radical Michael addition reactions of allylic or benzylic carbons.
Figure 8: Proposed mechanistic rationale for the observed chemoselectivities.
Scheme 13: The photocatalytic manipulation of C–H bonds adjacent to amine groups.
Scheme 14: The perylene-catalysed organophotoredox tandem difluoromethylation–acetamidation of styrene-type al...
Figure 9: Examples of biologically active molecules containing highly functionalised five membered heterocycl...
Scheme 15: The [3 + 2]-cycloaddition leading to the formation of pyrroles, through the reaction of 2H-azirines...
Figure 10: Proposed intermediate that determines the regioselectivity of the reaction.
Figure 11: Comparison of possible pathways of reaction and various intermediates involved.
Scheme 16: The acridinium salt-catalysed formation of oxazoles from aldehydes and 2H-azirines.
Scheme 17: The synthesis of oxazolines and thiazolines from amides and thioamides using organocatalysed photor...
Figure 12: Biologically active molecules on the market containing 1,3,4-oxadiazole moieties.
Scheme 18: The synthesis of 1,3,4-oxadiazoles from aldehyde semicarbazones using Eosin Y organophotocatalysis.
Scheme 19: The dimerization of primary thioamides to 1,2,4-thiadiazoles catalysed by the presence of Eosin Y a...
Scheme 20: The radical cycloaddition of o-methylthioarenediazonium salts and substituted alkynes towards the f...
Scheme 21: The dehydrogenative cascade reaction for the synthesis of 5,6-benzofused heterocyclic systems.
Figure 13: Trifluoromethylated version of compounds which have known biological activities.
Scheme 22: Eosin Y-catalysed photoredox formation of 3-substituted benzimidazoles.
Scheme 23: Oxidation of dihydropyrimidines by atmospheric oxygen using photoredox catalysis.
Scheme 24: Photoredox-organocatalysed transformation of 2-substituted phenolic imines to benzoxazoles.
Scheme 25: Visible light-driven oxidative annulation of arylamidines.
Scheme 26: Methylene blue-photocatalysed direct C–H trifluoromethylation of heterocycles.
Scheme 27: Photoredox hydrotrifluoromethylation of terminal alkenes and alkynes.
Scheme 28: Trifluoromethylation and perfluoroalkylation of aromatics and heteroaromatics.
Scheme 29: The cooperative asymmetric and photoredox catalysis towards the functionalisation of α-amino sp3 C–...
Scheme 30: Organophotoredox-catalysed direct C–H amidation of aromatics.
Scheme 31: Direct C–H alkylation of heterocycles using BF3K salts. CFL – compact fluorescent lamp.
Figure 14: The modification of camptothecin, demonstrating the use of the Molander protocol in LSF.
Scheme 32: Direct C–H amination of aromatics using acridinium salts.
Scheme 33: Photoredox-catalysed nucleophilic aromatic substitution of nucleophiles onto methoxybenzene derivat...
Scheme 34: The direct C–H cyanation of aromatics with a focus on its use for LSF.
