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Search for "mode of action" in Full Text gives 90 result(s) in Beilstein Journal of Organic Chemistry.
New advances in asymmetric organocatalysis II
- Radovan Šebesta
Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60
- , or sulfur. The year 2000 is typically regarded as the birth of organocatalysis, which was at that time regarded as a new mode of action for chemical catalysts. In that year, List and MacMillan et al. published their landmark studies on proline- and imidazolidine-catalyzed aldol, Mannich, and
Figure 1: TreeMap chart of the top 15 Web of Science categories for 6,700 articles containing the keywords “a...
Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines
- Sergio Torres-Oya and
- Mercedes Zurro
Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268
- example. This review discusses different examples involving IEDADA reactions and other cyclizations, with a special focus on the mode of action of the organocatalysts, and aims to show the synthetic applicability of the formed cyclic derivatives. The three non-covalent organocatalysts which will be
Graphical Abstract
Figure 1: Reactivity of α,β-unsaturated imines and variety of structures.
Figure 2: The hetero-Diels–Alder and inverse electron demand hetero-Diels–Alder reactions.
Figure 3: Different strategies to promote the activation of dienes and dienophiles in IEDADA reactions.
Figure 4: Examples of non-covalent interactions in organocatalysis.
Scheme 1: Enantioselective bifunctional thiourea-catalyzed inverse electron demand Diels–Alder reaction of N-...
Scheme 2: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2) reaction of α,β-unsaturated imines and ...
Scheme 3: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2)/(4 + 2) cascade reaction of α,β-unsatur...
Scheme 4: Enantioselective bifunctional squaramide-catalyzed formal [4 + 2] cycloaddition of malononitrile wi...
Scheme 5: Bifunctional squaramide-catalyzed IEDADA reaction of saccharin-derived 1-azadienes and azlactones.
Scheme 6: Chiral guanidine-catalyzed enantioselective (4+1) cyclization of benzofuran-derived azadienes with ...
Scheme 7: Bifunctional squaramide-catalyzed [4 + 2] cyclization of benzofuran-derived azadienes and azlactone...
Scheme 8: Chiral bifunctional squaramide-catalyzed domino Mannich/formal [4 + 2] cyclization of 2-benzothiazo...
Scheme 9: Chiral bifunctional thiourea-catalyzed formal IEDADA reaction of β,γ-unsaturated ketones and benzof...
Scheme 10: Dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates and ...
Scheme 11: Enantioselective squaramide-catalyzed asymmetric IEDADA reaction of benzofuran-derived azadienes an...
Scheme 12: Scale up and derivatizations of benzofuran-fused 2-piperidinol derivatives.
Scheme 13: Dihydroquinine-derived squaramide-catalyzed Mannich-type reaction of isocyanoacetates with N-(2-ben...
Figure 5: Structure of a cinchona alkaloid and (DHQD)2PHAL.
Scheme 14: Enantioselective modified cinchona alkaloid-catalyzed [4 + 2] annulation of γ-butenolides and sacch...
Scheme 15: Chiral tertiary amine-catalyzed [2 + 4] annulation of cyclic 1-azadiene with γ-nitro ketones.
Scheme 16: Inverse electron demand aza-Diels–Alder reaction (IEDADA) of 1-azadienes with enecarbamates catalyz...
Scheme 17: Phosphoric acid-catalyzed enantioselective [4 + 2] cycloaddition of benzothiazolimines and enecarba...
Scheme 18: Phosphoric acid-catalyzed enantioselective inverse electron demand aza-Diels–Alder reaction of in s...
Scheme 19: Proposed reaction mechanism for the phosphoric acid-catalyzed enantioselective inverse electron dem...
Scheme 20: Enantioselective dearomatization of indoles by a (3 + 2) cyclization with azoalkenes catalyzed by a...
Scheme 21: Synthetic applicability of the pyrroloindoline derivatives.
Scheme 22: Chiral phosphoric acid-catalyzed (2 + 3) dearomative cycloaddition of 3-alkyl-2-vinylindoles with a...
Scheme 23: Chiral phosphoric acid-catalyzed asymmetric [4 + 2] cycloaddition of aurone-derived 1-azadienes and...
Scheme 24: Phosphoric acid-catalyzed enantioselective formal [4 + 2] cycloaddition of dienecarbamates and 2-be...
Scheme 25: Chiral phosphoric acid-catalyzed asymmetric inverse electron demand aza-Diels–Alder reaction of 1,3...
Scheme 26: Chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and ...
Scheme 27: Synthetic applicability of the NPNOL derivatives.
Scheme 28: Chiral phosphoric acid-catalyzed asymmetric intermolecular formal (3 + 2) cycloaddition of azoalken...
Scheme 29: Enantioselective [4 + 2] cyclization of α,β-unsaturated imines and azlactones.
Scheme 30: Catalytic cycle for the chiral phosphoric acid-catalyzed enantioselective [4 + 2] cyclization of α,...
Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond
- Thomas Ma and
- John Chu
Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253
- of action (MOA) (e.g., membrane lysis and depolarization) [30][34] and specific MOA (e.g., dysregulation of ClpP protease [33], inhibition of topoisomerase I/II [36][68], blocking lipid II transport by flippase [29], sequestration of cell wall biosynthetic intermediate C55-(di)phosphate, etc.) [35
- molecules were screened for various bioactivities and led to the discovery of new antibiotics, antifungals, as well as anticancer compounds (Figure 4). Importantly, the underlying mechanism of bacterial growth suppression has been identified for several Syn-BNP antibiotics, which includes both general mode
Graphical Abstract
Figure 1: In BGF for microbial natural product discovery, the culture extract is fractionated using chromatog...
Figure 2: In light of BGF’s decreasing return-on-investment, scientists have developed new natural product di...
Figure 3: a) Incorporation of the first five amino acid BBs in daptomycin (highlighted in blue) is illustrate...
Figure 4: Syn-BNPs were synthesized in accordance to predicted NRP structures; shown herein are hits from var...
Figure 5: a) “Offloading” is the final step of NRP biosynthesis, wherein the mature NRP is released from the ...
N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity
- Peter Langer
Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240
- point to a completely different mode of action. In fact, the exact function of glycosylation is not clear. However, it might be assumed that the carbohydrate moiety increases the water solubility of the indirubin which results in a higher bioavailability of the drug. It might be speculated that the
Graphical Abstract
Scheme 1: Structures of indigo (1a), indirubin (2a) and isoindigo (3a).
Scheme 2: Structures of akashins A–C.
Scheme 3: Synthesis of 5b. Reagents and conditions: i) TMSOTf, 4 Å MS, CH2Cl2, −20 °C, 1.5 h, then 20 °C, 8–1...
Scheme 4: Synthesis of 7c. Reagents and conditions: i) TMSOTf, 4 Å MS, CH2Cl2, −18 °C, 3 h; then: TMSOTf, 4 Å...
Scheme 5: Synthesis of 1d. Reagents and conditions: i) chloroacetic acid, Na2CO3, reflux, 6 h; ii) Ac2O, NaOA...
Scheme 6: Synthesis of 10e. Reagents and conditions: i) p-TsOH·H2O, acetonitrile, MeOH, 1 d; ii) NIS, PPh3, D...
Scheme 7: Synthesis of akashins A–C. Reagents and conditions: i) TMSOTf, 4 Å MS, CH2Cl2, −18 to 20 °C, 15 h; ...
Scheme 8: Synthesis of 5d. Reagents and conditions: i) KMnO4, AcOH, high-power-stirring (12.000 rot/min), 20 ...
Scheme 9: Possible mechanism of the formation of 5c.
Scheme 10: Synthesis of 7d. Reagents and conditions: i) 1) CH2Cl2, 2) Me3SiI, 20 °C, 30 min, 3) 0 °C, 30 min, ...
Scheme 11: Synthesis of α-15b. Reagents and conditions: i) 1) CH2Cl2, 2) Me3SiI, 20 °C, 30 min, 3) 0 °C, 30 mi...
Scheme 12: Synthesis of isatin-N-glycosides 16a–f. Reagents and conditions: i) PhNH2, EtOH, 20 °C, 12 h; ii) Ac...
Scheme 13: Synthesis of 17–21. Reagents and conditions: i) Na2CO3, MeOH, 20 °C, 4 h.
Scheme 14: Synthesis of indirubin-N-glycosides α-17a and α-17b.
Scheme 15: Synthesis of β-17f. Reagents and conditions: i) 1) Na2CO3, MeOH, 20 °C, 4 h, 2) Ac2O/pyridine 1:1, ...
Scheme 16: Synthesis of β-24a. Reagents and conditions: i) n-PrOH, H2O, formic acid (buffer, 100 mM), 2 h, 65 ...
Scheme 17: Synthesis of isatin-N-glycosides 23b–g and 24b–g.
Scheme 18: Synthesis of β-29a,b. Reagents and conditions: i) EtOH, 20 °C, 12 h; ii) DDQ, dioxane, 20 °C, 12 h;...
Scheme 19: Synthesis of β-31a. Reagents and conditions: i) Na2SO3, dioxane, H2O, 110 °C, 2 d; ii) piperidine, ...
Scheme 20: Synthesis of 33a–d. Reagents and conditions: i) Ac2O, AcOH, NaOAc, 80 °C, 1 h; ii) 1) NaOMe, anhydr...
Scheme 21: Indirubins 34 and 35.
Scheme 22: Synthesis of 36f. Reagents and conditions: i) NaOH, H2O, 20 °C, 5 h; ii) HCl, NaNO2, H2O, −14 °C; i...
Scheme 23: Synthesis of 38a–h. Reagents and conditions: i) 1) 0.1 equiv NaOMe, MeOH, 20 °C, 15–20 min, 2) HOAc...
Scheme 24: Synthesis of 40a–h. Reagents and conditions: i) method A: EtOH/THF, cat. KOt-Bu, 20 °C, 3–4.5 h; me...
Scheme 25: Synthesis of 41a–d. Reagents and conditions: i) Ac2O, AcOH, NaOAc, 80 °C, 1 h.
Scheme 26: Synthesis of 41e. Reagents and conditions: i) AcOH, NaOAc, 110 °C, 24 h.
Scheme 27: Synthesis of E-β-43a–e and E-β-44a,b. Reagents and conditions: i) 1) NEt3, EtOH, 20 °C, 12 h, 2) DM...
Scheme 28: Synthesis of E-43f. Reagents and conditions: i) Na2CO3, MeOH, 20 °C, 6–24 h.
Scheme 29: Synthesis of 46a–m. Reagents and conditions: i) NEt3 (1 equiv), EtOH, 20 °C, 6–10 h; ii) MsCl, NEt3...
Scheme 30: Synthesis of 48a–d. Reagents and conditions: i) AcOH/Ac2O, NaOAc, 60 °C, 3–4 h.
Scheme 31: Synthesis of 48e. Reagents and conditions: i) NaOAc, AcOH, 110 °C, 24 h.
Scheme 32: Synthesis of β-49a,b. Reagents and conditions: i) AcOH/Ac2O, NaOAc, 60 °C, 3–4 h.
Scheme 33: Synthesis of β-54a,b. Reagents and conditions: i) 1) NaH, DMF, 0 °C, 15 min, 2) β-51a,b, 20 °C, 3 h...
Scheme 34: Synthesis of 54c–l. The yields refer to the yields of the first and second condensation step for ea...
Scheme 35: Synthesis of 57a–c and 58a–d. Reagents and conditions: i) HCl (conc.), AcOH, reflux, 24 h; ii) 1) B...
Scheme 36: Synthesis of 59a–e and 60a–e. Reagents and conditions: i) P(NEt2)3 (1.1 equiv), CH2Cl2, −78 °C to 2...
Scheme 37: Synthesis of 61a–d and 62a–d. Reagents and conditions: i) P(NEt2)3 (1.1 equiv), CH2Cl2, −78 °C to 2...
Scheme 38: Synthesis of β-64a–e and α-64a. Reagents and conditions: i) AcOH, Ac2O, NaOAc, 90 °C, 6 h.
Scheme 39: Synthesis of β-72a. Reagents and conditions: i) 66, EtOH, 20 °C, 12 h; ii) DDQ, dioxane, 20 °C, 12 ...
Scheme 40: Synthesis of β-72b.
Scheme 41: Synthesis of β-74a–c. Reagents and conditions: i) AcOH, Ac2O, NaOAc, 130 °C, 2 d.
Scheme 42: Synthesis of β-77. Reagents and conditions: i) 1) NEt3, EtOH, 20 °C, 12 h, 2) DMAP, NEt3, MsCl, 0 °...
Scheme 43: Synthesis of β-81a–f and β-80g. Reagents and conditions: i) AcOH, 80 °C, 1–3 h; ii) benzene, PTSA, ...
Scheme 44: Synthesis of 84a. Reagents and conditions: i) benzene, AlCl3, 20 °C, 10 min; ii) MeOH, NaOMe, 12 h,...
Scheme 45: Synthesis of 84b–l. The yields refer to the yields of the condensation and the deprotection step fo...
Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide
- Parvathy Mini,
- Michael R. Grace,
- Genevieve H. Dennison and
- Kellie L. Tuck
Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237
- ), anion/sulfur compound (50 µM) and Na2S (15 µM), n = 3. Chemical structure and mode of action of [Tb(DPA-N3)3]3− for detection of H2S(g) [11]. Synthesis of Tb.1. Binding constant determination for the 1:1 host–guest interaction (Tb.1 + Cu2+ ions), determined using supramolecular.org [18]. Supporting
Graphical Abstract
Figure 1: Previously reported lanthanide complexes [12,16,17].
Scheme 1: Synthesis of Tb.1.
Figure 2: Absorption (red line), excitation (yellow line, λem = 615 nm), and emission (green line, λex = 250 ...
Figure 3: (a) Changes in the luminescence emission spectrum of 5 µM [Tb.1·3Cu]3+ upon the addition of Na2S (0...
Figure 4: (a) Changes in the luminescence emission spectrum of 5 µM [Tb.1·3Cu]3+ upon the addition of Na2S (0...
Figure 5: Luminescence intensity of 5 μM Tb.1 in 10 mM Tris-HCl buffer, pH 7.4, containing 5% DMSO upon the a...
Figure 6: Changes in luminescent intensity of [Tb.1·3Cu]3+ (5 µM) detected at 545 nm in the presence of vario...
Figure 7: Chemical structure and mode of action of [Tb(DPA-N3)3]3− for detection of H2S(g) [11].
2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space
- Carlos Nieto,
- Alejandro Manchado,
- Ángel García-González,
- David Díez and
- Narciso M. Garrido
Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163
- toxicity reports in hospital admissions. Nguyen et al. [36] investigated its effects in mice, demonstrating neurotoxicity via dopamine receptors, while Tuv et al. [37] studied the compound’s phamarcokinetics, pharmacodynamics, and mode of action in comparison to methamphetamine, which revealed a
- significantly lower potency of 32. Ulotaront (33, SEP-363856) [38] is a phase-3 clinical lead for the treatment of schizophrenia, displaying TAAR1 (trace-amine-associated receptor 1) [39] and 5-HT1A agonism as mode of action, lacking dopamine D2 and 5-HT2A antagonism. SAR exploration of the ulotaront family was
Graphical Abstract
Scheme 1: Description of the 2-heteroarylethylamine scope of the present review featuring appropriate heteroa...
Scheme 2: 2-Aminoethylpyridine derivatives with therapeutic activity.
Scheme 3: 2-Aminoethylfuran derivatives with therapeutic activity.
Scheme 4: 2-Aminoethylthiophene derivatives with therapeutic activity, part 1.
Scheme 5: 2-Aminoethylthiophene derivatives with therapeutic activity, part 2.
Scheme 6: 2-Aminoethylthiophene derivatives with therapeutic activity, part 3.
Scheme 7: 2-Aminoethylpyrrole derivatives with therapeutic activity.
Scheme 8: Histamine metabolic pathway.
Scheme 9: 2-Aminoethylimidazole derivatives with therapeutic activity, part 1. Krel is referred as histamine ...
Scheme 10: Conformationally restricted 2-aminoethylimidazole derivatives with therapeutic activity, part 2.
Scheme 11: 2-Aminoethylimidazole derivatives with therapeutic activity, part 3.
Scheme 12: 2-Aminoethylimidazole derivatives with therapeutic activity, part 4.
Scheme 13: 2-Aminoethylpyrazole derivatives with therapeutic activity.
Scheme 14: 2-Aminoethylisoxazole derivatives with therapeutic activity.
Scheme 15: 2-Aminoethylthiazole derivatives with therapeutic activity.
Scheme 16: 2-Aminoethyloxadiazole derivatives with therapeutic activity.
Scheme 17: 2-Aminoethyltriazole derivatives with therapeutic activity.
Scheme 18: 2-Aminoethyloxadiazole derivatives with therapeutic activity.
Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry
- Maria-Paula Schröder,
- Isabel P.-M. Pfeiffer and
- Silja Mordhorst
Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147
- spectrum and loses all activity when unmethylated. Although the mode of action is unclear, the methylations are essential to the bioactivity. CypM methylates many oligopeptides that mimic the cypemycin N-terminal sequence, and unrelated peptide antibiotics. Additionally, CypM methylates short oligopeptides
Graphical Abstract
Figure 1: Schematic representation of the different acceptor regions for the methylation of RiPPs discussed i...
Figure 2: Schematic overview of different methylation strategies for amino acids and peptides. There are seve...
Figure 3: Biological methylation. A) Methyl donors from biological systems. The transferred methyl group is h...
Figure 4: Chemical structures of RiPPs with diverse O-, N-, C-, and S-methylations. Amino acids of lassomycin...
Figure 5: The three-dimensional structures of the conventional O-MTs OlvSA (model structure calculated by Col...
Figure 6: Reaction scheme of the PAMT´s catalysis, leading to the enzymatic conversion of aspartate to aspart...
Figure 7: Structural organisation of the OphMA homodimer. A) Schematic representation. The MT domain is colou...
Figure 8: Overview of the protein architectures and core peptide compositions of borosin N-MTs as defined by ...
Figure 9: Radical SAM C-methyltransferases. A) The different rSAM MT classes containing different functional ...
Figure 10: The three-dimensional structures of the rSAM C-MTs TsrM with bound cobalamin and [4Fe-4S] cluster (...
Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis
- Johannes Rocker,
- Till J. B. Zähringer,
- Matthias Schmitz,
- Till Opatz and
- Christoph Kerzig
Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106
- thorough photochemical characterization is essential for efficient light-driven applications. In this article, the mode of action of a polyazahelicene catalyst (Aza-H) was investigated using laser flash photolysis (LFP). The study revealed that the chromophore can function as a singlet-state photoredox
Graphical Abstract
Scheme 1: Left: Reaction mechanism of the 3-CR with Aza-H as the photocatalyst. Potentials are given vs SCE. ...
Figure 1: A) Room-temperature absorption (black) and emission (yellow) spectra of Aza-H recorded in MeCN/H2O ...
Figure 2: Mechanistic LFP experiments of 25 µM Aza-H with 4CP in MeCN/H2O (9:1) after 355 nm laser pulses. A)...
Figure 3: Mechanistic investigations of Aza-H with TsNa by LFP studies. A) Transient absorption measurements ...
Figure 4: Data sets employed for the calculation ΦISC of Aza-H based on the ground state bleach of Rubpy as t...
Figure 5: Stilbene isomerization and additional energy transfer experiments. A) and B) Triplet quenching expe...
The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids
- Carolina S. Marques,
- Aday González-Bakker and
- José M. Padrón
Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104
- . Overall, the results of the biological activity allow speculating that the compounds from the series 8a–n might exhibit diverse mode of actions. Taking all these considerations as a whole, further studies of the biological activity of compounds 8d, 8h and 8k might provide insights into the mode of action
- , in a fast and clean reaction process. Among the library of α-acetamide carboxamide isatin hybrids, 14 were tested regarding their antiproliferative activity. Compounds 8d, 8h and 8k were found to be the most potent ones, with GI50 values in the range of 1–10 μM. Further studies on the mode of action
Graphical Abstract
Figure 1: (A) Accessing libraries of oxindole hybrids using commercially available isatin as starting materia...
Scheme 1: (A) Library of isatin-based α-acetamide carboxamide oxindole derivatives obtained using an Ugi four...
Scheme 2: Library of α-acetamide carboxamide oxindole hybrids 5 accessed via the Ugi4CR.
Figure 2: Carboxylic acids 2 and aldehydes/ketones 3 used in the Ugi4CR.
Scheme 3: Microwave-assisted CuAAC reaction to access α-acetamide carboxamide 1,2,3-triazole oxindole hybrid 7...
Scheme 4: Library of α-acetamide carboxamide isatin hybrids 8 easy accessed via deprotection reaction on the ...
Figure 3: GI50 range plot against human solid tumor cell lines of investigated α-acetamide carboxamide isatin...
Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors
- Jens Frackenpohl,
- David M. Barber,
- Guido Bojack,
- Birgit Bollenbach-Wahl,
- Ralf Braun,
- Rahel Getachew,
- Sabine Hohmann,
- Kwang-Yoon Ko,
- Karoline Kurowski,
- Bernd Laber,
- Rebecca L. Mattison,
- Thomas Müller,
- Anna M. Reingruber,
- Dirk Schmutzler and
- Andrea Svejda
Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46
- relationship (SAR) studies on selective inhibitors reduce the prevalence of undesired effects, such as toxicity in mammals [4]. Despite being employed in the field for over three decades, the mode of action of preemergence herbicide cinmethylin (1, Scheme 1) has remained unknown until 2018. At that time, the
- shown good results in selectively controlling grass weeds in both cool and warm seasons [7][8][9]. Recently, it has been shown that several herbicides bearing a gem-dimethylbenzylamide motif, e.g., cumyluron (3a) and oxaziclomefone (3b), previously exhibiting an unknown mode of action, control weeds due
Graphical Abstract
Scheme 1: Selected known inhibitors 1–3 of acyl-ACP thioesterases (belonging to the protein family of FATs) a...
Scheme 2: Preparation of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 7a–c and 13a–c via iron-mediated sulfur rem...
Scheme 3: Evaluation of potential side reactions in the borane-mediated preparation of 2,3-dihydro[1,3]thiazo...
Figure 1: Preemergence efficacy of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine-based FAT inhibitors 7b, 7c, and 1...
Figure 2: Preemergence efficacy of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine-based FAT inhibitors 7b, 7c, and 1...
Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials
- Jessica Villegas,
- Bryce C. Ball,
- Katelyn M. Shouse,
- Caleb W. VanArragon,
- Ashley N. Wasserman,
- Hannah E. Bhakta,
- Allen G. Oliver,
- Danielle A. Orozco-Nunnelly and
- Jeffrey M. Pruet
Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108
- telomerase and topoisomerases I and II [15][19][20]. It is evident that the effects of berberine are not tied to any single mode of action. Chelerythrine has also been shown to possess a wide variety of biological activities, such as anticancer, antibacterial, and anti-inflammatory actions [11][21][22][23
- , while the remaining variants resulted in either equal or lower concentrations of measured ALP levels (using a Mann–Whitney U Test and a significance cutoff of P ≤ 0.05). These results suggest intercellular protein leakage is not the primary mode of action for the improved activity seen in our variants
Graphical Abstract
Figure 1: Zones of inhibition for 1 mg of evaporated methanolic (MeOH) extracts from various parts of the A. ...
Scheme 1: General route to berberine variants, displaying the numbering system for the berberine ring.
Scheme 2: Synthesis of new berberine variants. Reductive amination to a secondary amine was followed by cycli...
Figure 2: X-ray crystal structures of the oxidation byproducts a) B4 (CCDC 2271457) and b) B6 (CCDC 2271458; ...
Scheme 3: Direct modification of the original berberine structure.
Scheme 4: Preparation of non-cyclic charged variants of B1.
Scheme 5: Partial reduction of compound B1 to B14.
Figure 3: Kirby–Bauer zones of inhibition for all variants B1–B14 compared to original berberine (B). Mean zo...
Scheme 6: Synthesis of the substituted 2-bromoaminonaphthalenes 9 and 10.
Scheme 7: Completion of the synthesis of variants C1–C4.
Figure 4: Kirby–Bauer zones of inhibition for variants C1–C4 compared to original chelerythrine (C). Mean zon...
Figure 5: Effects of original berberine and all variants against T84 human colon cancer cells. Cells were tre...
Figure 6: Effects of original chelerythrine and all variants against T84 human colon cancer. Cells were treat...
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- noted that ELs are essential players of cell signaling [25]. Together, all these studies point out that ELs are essential for a multitude of biological functions [26] despite their mode of action is not yet fully understood. From a molecular point of view, the ether function present in alkenyl ELs
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites
- Houchao Xu,
- Anne Wochele,
- Minghe Luo,
- Gregor Schnakenburg,
- Yuhui Sun,
- Heike Brötz-Oesterhelt and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120
- temperature. Also the addition of base (NEt3) did not promote the reaction. Therefore, the mode of action of TDD towards glutathione S-transferase needs further investigation. Conclusion We have established an efficient synthesis of TDD that makes this compound available from ʟ-tryptophan with a high yield of
Graphical Abstract
Scheme 1: Structures of hangtaimycin (1) and its co-metabolites.
Scheme 2: First synthetic route towards TDD (4).
Figure 1: HPLC analyses of (Z)-4 on a chiral stationary phase. A) Nearly racemic 4 from the first synthetic r...
Scheme 3: Second synthetic route towards TDD ((Z)-4).
Figure 2: X-ray structure of (rac)-4.
Figure 3: Bioactivity testing with hangtaimycin (1). A) Growth retardation of model species B. subtilis 168 a...
Synthesis and late stage modifications of Cyl derivatives
- Phil Servatius and
- Uli Kazmaier
Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19
- naturally occurring HDAC inhibitors are known to date [12]. Acyclic molecules like, e.g., trichostatin A (TSA, Figure 1) were among the first isolated HDAC inhibitors. Isolated in 1976 from Streptomyces hygroscopicus by Tsuji et al. [13], TSA played an important role in rationalizing the mode of action of
Graphical Abstract
Figure 1: Naturally occurring HDAC inhibitors.
Figure 2: Naturally occurring HDAC inhibitors with different zinc-binding motifs.
Scheme 1: Planned syntheses of Cyl-1 derivatives.
Scheme 2: Cyl-1 derivatives via peptide Claisen rearrangement.
Scheme 3: Synthesis of tetrapeptide allyl esters 8.
Scheme 4: Synthesis and late stage modifications of Cyl derivatives.
N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts
- Viera Poláčková,
- Dominika Krištofíková,
- Boglárka Némethová,
- Renata Górová,
- Mária Mečiarová and
- Radovan Šebesta
Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176
- influence on the catalytic reactions. Under ball-milling conditions, the Michael adducts were obtained in good yields but with slightly lower enantiomeric purities than in solution. DFT calculations elucidated its mode of action and confirmed a dual activation mode, which combines enamine activation of
- have evaluated the suitability of these catalysts under solvent-free conditions. With the help of DFT calculations, we elucidated the mode of action of these catalysts. Results and Discussion Synthesis of catalysts We have started the synthesis of the catalysts from Boc-protected (S)-prolinol (1), from
Graphical Abstract
Figure 1: Catalyst design principles.
Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
Scheme 3: Synthesis of adducts 8a,d,f in solution.
Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction
- Dušan Đ. Škorić,
- Olivera R. Klisurić,
- Dimitar S. Jakimov,
- Marija N. Sakač and
- János J. Csanádi
Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174
- mutually very similar mode of action. Looking at the cytotoxicity dose dependence of 7, 23, and 24 on MDA-MB-231 cell line (Figure 4B), it could be seen that it is not completely linear. At a concentration greater than 1 µM, cytotoxicity did not increase at the same rate but a plateau-like curve was formed
Graphical Abstract
Figure 1: Structures of the steroidal tetrazoles that showed anticancer potential in vitro.
Figure 2: Mechanism of the Schmidt reaction.
Scheme 1: Synthesis of 12-oxo intermediates. Reagents and conditions: a) EtOAc, pTsOH, reflux, 14 h (81%); b)...
Scheme 2: Synthesis of 7-oxo intermediate 11 from chenodeoxycholic acid (9). Reagents and conditions: a) EtOA...
Figure 3: Mercury [51] drawing of the molecular structures of compounds 13 and 14, with labelling of nonhydrogen ...
Figure 4: Dose dependence of the cytotoxicity of tested compounds on treated cell lines. All compounds were t...
Photoredox catalysis in nickel-catalyzed C–H functionalization
- Lusina Mantry,
- Rajaram Maayuri,
- Vikash Kumar and
- Parthasarathy Gandeepan
Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143
- for the mode of action of this cascade arylation protocol (Figure 10) [73]. In the photocatalytic cycle, the SET event between the photoexcited iridium catalyst 10-II and the substrate oxalate 33 generates a tertiary carbon-centered radical 10-IV by decarboxylation and the reduced iridium(II
Graphical Abstract
Scheme 1: Nickel-catalyzed cross-coupling versus C‒H activation.
Figure 1: Oxidative and reductive quenching cycles of a photocatalyst. [PC] = photocatalyst, A = acceptor, D ...
Scheme 2: Photoredox nickel-catalyzed C(sp3)–H arylation of dimethylaniline (1a).
Scheme 3: Photoredox nickel-catalyzed arylation of α-amino, α-oxy and benzylic C(sp3)‒H bonds with aryl bromi...
Figure 2: Proposed catalytic cycle for the photoredox-mediated HAT and nickel catalysis enabled C(sp3)‒H aryl...
Scheme 4: Photoredox arylation of α-amino C(sp3)‒H bonds with aryl iodides.
Figure 3: Proposed mechanism for photoredox nickel-catalyzed α-amino C‒H arylation with aryl iodides.
Scheme 5: Nickel-catalyzed α-oxy C(sp3)−H arylation of cyclic and acyclic ethers.
Figure 4: Proposed catalytic cycle for the C(sp3)−H arylation of cyclic and acyclic ethers.
Scheme 6: Photochemical nickel-catalyzed C–H arylation of ethers.
Figure 5: Proposed catalytic cycle for the nickel-catalyzed arylation of ethers with aryl bromides.
Scheme 7: Nickel-catalyzed α-amino C(sp3)‒H arylation with aryl tosylates.
Scheme 8: Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols.
Scheme 9: Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13).
Scheme 10: Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold.
Figure 6: Proposed mechanism for C(sp3)–H arylation through dual polyoxometalate HAT and nickel catalytic man...
Scheme 11: Photochemical nickel-catalyzed α-hydroxy C‒H arylation.
Scheme 12: Photochemical synthesis of fluoxetine (21).
Scheme 13: Photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl bromides.
Figure 7: Proposed mechanism for the photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl brom...
Scheme 14: Photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and nickel catalysis.
Figure 8: Proposed mechanism for photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and ...
Scheme 15: Benzophenone- and nickel-catalyzed photoredox benzylic C–H arylation.
Scheme 16: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)–H arylation.
Scheme 17: Photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Figure 9: Proposed mechanism for the photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Scheme 18: Photoredox nickel-catalyzed α-(sp3)‒H arylation of secondary benzamides with aryl bromides.
Scheme 19: Enantioselective sp3 α-arylation of benzamides.
Scheme 20: Nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxalates.
Figure 10: Proposed mechanism for the nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxal...
Scheme 21: C(sp3)−H arylation of bioactive molecules using mpg-CN photocatalysis and nickel catalysis.
Figure 11: Proposed mechanism for the mpg-CN/nickel photocatalytic C(sp3)–H arylation.
Scheme 22: Nickel-catalyzed synthesis of 1,1-diarylalkanes from alkyl bromides and aryl bromides.
Figure 12: Proposed mechanism for photoredox nickel-catalyzed C(sp3)–H alkylation via polarity-matched HAT.
Scheme 23: Photoredox nickel-catalyzed C(sp3)‒H alkylation via polarity-matched HAT.
Scheme 24: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of ethers.
Scheme 25: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of amides and thioethers.
Scheme 26: Photoredox and nickel-catalyzed C(sp3)‒H alkylation of benzamides with alkyl bromides.
Scheme 27: CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers with alkyl bromides.
Figure 13: Proposed mechanism for the CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers.
Scheme 28: Nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides and acid chlorides using trimethy...
Figure 14: Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides ...
Scheme 29: Photochemical nickel-catalyzed C(sp3)–H methylations.
Scheme 30: Photoredox nickel catalysis-enabled alkylation of unactivated C(sp3)–H bonds with alkyl bromides.
Scheme 31: Photochemical C(sp3)–H alkenylation with alkenyl tosylates.
Scheme 32: Photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Figure 15: Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Scheme 33: Photoredox nickel-catalyzed hydroalkylation of activated alkynes with C(sp3)−H bonds.
Scheme 34: Allylation of unactivated C(sp3)−H bonds with allylic chlorides.
Scheme 35: Photochemical nickel-catalyzed α-amino C(sp3)–H allylation of secondary amides with trifluoromethyl...
Scheme 36: Photoredox δ C(sp3)‒H allylation of secondary amides with trifluoromethylated alkenes.
Scheme 37: Photoredox nickel-catalyzed acylation of α-amino C(sp3)‒H bonds of N-arylamines.
Figure 16: Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H bonds of N-ary...
Scheme 38: Photocatalytic α‑acylation of ethers with acid chlorides.
Figure 17: Proposed mechanism for the photocatalytic α‑acylation of ethers with acid chlorides.
Scheme 39: Photoredox and nickel-catalyzed C(sp3)‒H esterification with chloroformates.
Scheme 40: Photoredox nickel-catalyzed dehydrogenative coupling of benzylic and aldehydic C–H bonds.
Figure 18: Proposed reaction pathway for the photoredox nickel-catalyzed dehydrogenative coupling of benzylic ...
Scheme 41: Photoredox nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic ac...
Scheme 42: Nickel-catalyzed C(sp3)‒H acylation with N-acylsuccinimides.
Figure 19: Proposed mechanism for the nickel-catalyzed C(sp3)–H acylation with N-acylsuccinimides.
Scheme 43: Nickel-catalyzed benzylic C–H functionalization with acid chlorides 45.
Scheme 44: Photoredox nickel-catalyzed benzylic C–H acylation with N-acylsuccinimides 84.
Scheme 45: Photoredox nickel-catalyzed acylation of indoles 86 with α-oxoacids 87.
Scheme 46: Nickel-catalyzed aldehyde C–H functionalization.
Figure 20: Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization.
Scheme 47: Photoredox carboxylation of methylbenzenes with CO2.
Figure 21: Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2.
Scheme 48: Decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization.
Figure 22: Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunc...
Scheme 49: Diaryl ketone HAT catalysis and nickel catalysis enabled dicarbofunctionalization of alkenes.
Figure 23: Proposed catalytic mechanism for the diaryl ketone HAT catalysis and nickel catalysis enabled dicar...
Scheme 50: Overview of photoredox nickel-catalyzed C–H functionalizations.
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
- enzymes available for polysaccharide synthesis and their mode of action was recently published [11]. Despite the numerous advantages of this approach, limited enzyme availability as well as their high specificity narrowed the substrate scope. Generally, the highly specific enzyme reactive site tolerates
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications
- Christopher Liczner,
- Kieran Duke,
- Gabrielle Juneau,
- Martin Egli and
- Christopher J. Wilds
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
- , the natural DNA sequence had a half-life of 1 min [202]. The incorporation of fluorine at the C4' position has long constituted a challenge owing to the instability of the glycosidic bond in the resulting nucleosides. This modification is desirable due to its involvement in the mode of action of the
Graphical Abstract
Figure 1: Structures of the chemically modified oligonucleotides (A) N3' → P5' phosphoramidate linkage, (B) a...
Scheme 1: Synthesis of a N3' → P5' phosphoramidate linkage by solid-phase synthesis. (a) dichloroacetic acid;...
Figure 2: Crystal structures of (A) N3' → P5' phosphoramidate DNA (PDB ID 363D) [71] and (B) amide (AM1) RNA in c...
Scheme 2: Synthesis of a phosphorodithioate linkage by solid-phase synthesis. (a) detritylation; (b) tetrazol...
Figure 3: Close-up view of a key interaction between the PS2-modified antithrombin RNA aptamer and thrombin i...
Scheme 3: Synthesis of the (S)-GNA thymine phosphoramidite from (S)-glycidyl 4,4'-dimethoxytrityl ether. (a) ...
Figure 4: Surface models of the crystal structures of RNA dodecamers with single (A) (S)-GNA-T (PDB ID 5V1L) [54]...
Figure 5: Structures of 2'-O-alkyl modifications. (A) 2'-O-methoxy RNA (2'-OMe RNA), (B) 2'-O-(2-methoxyethyl...
Scheme 4: Synthesis of the 2'-OMe uridine from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine. (a) Benzoy...
Scheme 5: Synthesis of the 2'-O-MOE uridine from uridine. (a) (PhO)2CO, NaHCO3, DMA, 100 °C; (b) Al(OCH2CH2OCH...
Figure 6: Structure of 2'-O-(2-methoxyethyl)-RNA (MOE-RNA). (A) View into the minor groove of an A-form DNA d...
Figure 7: Structures of locked nucleic acids (LNA)/bridged nucleic acids (BNA) modifications. (A) LNA/BNA, (B...
Scheme 6: Synthesis of the uridine LNA phosphoramidite. (a) i) NaH, BnBr, DMF, ii) acetic anhydride, pyridine...
Scheme 7: Synthesis of the 2'-fluoroarabinothymidine. (a) 30% HBr in acetic acid; (b) 2,4-bis-O-(trimethylsil...
Figure 8: Sugar puckers of arabinose (ANA) and arabinofluoro (FANA) nucleic acids compared with the puckers o...
Figure 9: Structures of C4'-modified nucleic acids. (A) 4'-methoxy, (B) 4'-(2-methoxyethoxy), (C) 2',4'-diflu...
Scheme 8: Synthesis of the 4'-F-rU phosphoramidite. (a) AgF, I2, dichloromethane, tetrahydrofuran; (b) NH3, m...
Scheme 9: Synthesis of the thymine FHNA phosphoramidite. (a) thymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, ace...
Scheme 10: Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyrid...
Figure 10: Crystal structures of (A) FHNA and (B) Ara-FHNA in modified A-form DNA decamers (PDB IDs 3Q61 and 3...
Simulating the enzymes of ganglioside biosynthesis with Glycologue
- Andrew G. McDonald and
- Gavin P. Davey
Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64
- substrate. The formal language on which the method is based is a modelling language for glycosyltransferases, and can be used to classify the types of reaction catalyzed according to simple rules. We identify extension of a linear oligosaccharide as the default mode of action (Equation 1), where x and y are
Graphical Abstract
Figure 1: Chemical structure of ganglioside GM1a (a β-ᴅ-galactosyl-(1→3)-N-acetyl-β-ᴅ-galactosaminyl-(1→4)-[α-...
Figure 2: Construction of the Svennerholm name GP1cα from its Glycologue structure identifier. At each step o...
Figure 3: Ganglioside carbohydrates predicted by the model. All structures are linked to ceramide at the base...
Figure 4: Ganglioside biosynthetic reaction network predicted by the Glycologue enzyme simulator. Starting fr...
Figure 5: Predicted effects on the pathways of ganglioside biosynthesis when individual enzyme activities are...
19F NMR as a tool in chemical biology
- Diana Gimenez,
- Aoife Phelan,
- Cormac D. Murphy and
- Steven L. Cobb
Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28
- of an in-depth understanding of their function and mode of action. Owing to the large size of biomacromolecules, the high complexity of the processes in which they participate and the natural environment in which they occur, an integrated analytical approach is often required to succeed in revealing
Graphical Abstract
Figure 1: Selected examples of 19F-labelled amino acid analogues used as probes in chemical biology.
Figure 2: (a) Sequences of the antimicrobial peptide MSI-78 and pFtBSer-containing analogs and cartoon repres...
Figure 3: (a) Chemical structures of a selection of trifluoromethyl tags. (b) Comparative analysis showing th...
Figure 4: (a) First bromodomain of Brd4 with all three tryptophan residues displayed in blue and labelled by ...
Figure 5: (a) Enzymatic hydroxylation of GBBNF in the presence of hBBOX (b) 19F NMR spectra showing the conve...
Figure 6: (a) In-cell enzymatic hydrolysis of the fluorinated anandamide analogue ARN1203 catalyzed by hFAAH....
Figure 7: (a) X-ray crystal structure of CAM highlighting the location the phenylalanine residues replaced by...
Figure 8: 19F PREs of 4-F, 5-F, 6-F, 7-FTrp49 containing MTSL-modified S52CCV-N. The 19F NMR resonances of ox...
Figure 9: 19F NMR as a direct probe of Ud NS1A ED homodimerization. Schematic representation showing the loca...
Figure 10: (a) Representative spectrum of a 182 μM sample of Aβ1-40-tfM35 at varying times indicating the majo...
Figure 11: Illustration of the conformational switch induced by SDS in 4-tfmF-labelled α-Syn. Also shown are t...
Figure 12: (a) Structural models of the Myc‐Max (left), Myc‐Max‐DNA (middle) and Myc‐Max‐BRCA1 complexes (righ...
Figure 13: (a) Side (left) and bottom (right) views of the pentameric apo ELIC X-ray structure (PDB ID: 3RQU) ...
Figure 14: (a) General structure of a selection of recently developed 19F-labelled nucleotides for their use a...
Figure 15: Monitoring biotransformation of the fluorinated pesticide cyhalothrin by the fungus C. elegans. The...
Figure 16: Following the biodegradation of emerging fluorinated pollutants by 19F NMR. The spectra are from cu...
Figure 17: Discovery of new fluorinated natural products by 19F NMR. The spectrum is of the culture supernatan...
Figure 18: Application of 19F NMR to investigate the biosynthesis of nucleocidin. The spectra are from culture...
Figure 19: Detection of new fluorofengycins (indicated by arrows) in culture supernatants of Bacillus sp. CS93...
Figure 20: Measurement of β-galactosidase activity in MCF7 cancer cells expressing lacZ using 19F NMR. The deg...
Figure 21: Detection of ions using 19F NMR. (a) Structure of TF-BAPTA and its 19F iCEST spectra in the presenc...
Figure 22: (a) The ONOO−-mediated decarbonylation of 5-fluoroisatin and 6-fluoroisatin. The selectivity of (b)...
NMR Spectroscopy of supramolecular chemistry on protein surfaces
- Peter Bayer,
- Anja Matena and
- Christine Beuck
Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203
- multimeric proteins like the hexameric AAA+ ATPase p97 [124]. Furthermore, methyl-TROSY-HMQC has been employed to investigate the allosteric mode of action of the synthetic inhibitor filibuvir to the selectively Ileδ1 methyl-labeled hepatitis C virus RNA polymerase NS5B [125]. This study also includes a good
Graphical Abstract
Figure 1: Ligands targeting charged areas on protein surfaces discussed in this review. The protein shown as ...
Figure 2: 1H NMR titration of lysine with tweezers. All signals show chemical shift perturbations and differe...
Figure 3: 1H,15N-HSQC Titration of full-length hPin1 with supramolecular tweezers (original data). (a) Spectr...
Figure 4: Relative signal intensities can be used to identify ligand binding sites (schematic representation ...
Figure 5: Schematic 1H,15N-HSQC spectrum of tauF4 (chemical shifts from BMRB # 17945, [109]) with and without spec...
Figure 6: H2(C)N spectra specific for arginine (a) and lysine (b) residues of the hPin1-WW domain at differen...
Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A
- Zhishu Zeng,
- Jun Xie,
- Guangyan Luo,
- Zhu Tao and
- Qianjun Zhang
Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194
- that the molecular size of the flavonoids and the length of the sugar chains have a greater impact on the assembly mode of supramolecular systems. Results and Discussion Host–guest interactions The host–guest interaction can be effectively observed using 1H NMR spectroscopy, and the mode of action of
Graphical Abstract
Figure 1: The molecular structure of OA (A) and Q[8] (B).
Figure 2: 1H NMR titration of OA with Q[8] were performed in D2O containing 10% DMSO by volume, OA (500 μmol·L...
Figure 3: (A) The UV–vis absorption spectra recorded for OA in the presence of Q[8] (c(Q[8]), labeled a–k: 0,...
Figure 4: IR spectra recorded for (a) Q[8], (b) OA, (c) a physical mixture of Q[8] and OA, and (d) the OA@Q[8...
Figure 5: The possible interaction mode for OA@Q[8].
Figure 6: The phase-solubility graph obtained for OA in a Q[8] aqueous solution at λ = 275 nm.
Figure 7: The clearance rate curve of ABTS+• upon increasing the concentration of OA and the OA@Q[8] inclusio...
Figure 8: The release curves of OA and OA@Q[8].
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
- light as a cheap and economic energy source. In this way, these strategies follow the requirements of environment-friendly chemistry. Regarding intrinsic advantages as well as the complementary mode of action of the two catalytic transformations previously introduced, their merging in a synergistic dual
- synthesis. The mechanistic studies suggested a unique mode of action of this catalytic system (Figure 45). In the initial step both aromatic coupling partners coordinate to the Mn catalyst, thus generating a photoactive complex. Visible-light photoexcitation of the Ar–Mn species and subsequent electron
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Fabclavine diversity in Xenorhabdus bacteria
- Sebastian L. Wenski,
- Harun Cimen,
- Natalie Berghaus,
- Sebastian W. Fuchs,
- Selcuk Hazir and
- Helge B. Bode
Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84
- the anterior midgut of larvae [43]. Consequently, this mode of action could also be possible for fabclavines. Conclusion This study revealed a large chemical diversity for fabclavine derivatives among different Xenorhabdus strains, which is achieved by the promiscuity of single enzymes or domains
Graphical Abstract
Figure 1: General biosynthesis of fabclavine Ia (1) in X. budapestensis (A) and representation of a shortened...
Figure 2: Comparison of the fcl BGCs in Xenorhabdus and Photorhabdus strains responsible for the fabclavine b...
