Search results
Search for "AIDS" in Full Text gives 50 result(s) in Beilstein Journal of Organic Chemistry.
Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts
- Ritu Mamgain,
- Kokila Sakthivel and
- Fateh V. Singh
Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243
- assist in the deprotonation of intermediate II to produce final products 27, while K2S2O8 aids in the oxidation of the photocatalyst in the case of pyridine N-oxide. In another photoinduced reaction procedure, Murarka et al. reported the formation of aryl radicals from a tetrameric electron donor
Graphical Abstract
Figure 1: Various structures of iodonium salts.
Scheme 1: Αrylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides 7 and α-fluoroacetamides 8...
Scheme 2: Proposed mechanism for the arylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides ...
Scheme 3: α-Arylation of α-nitro- and α-cyano derivatives of α-fluoroacetamides 9 employing unsymmetrical DAI...
Scheme 4: Synthesis of α,α-difluoroketones 13 by reacting α,α-difluoro-β-keto acid esters 11 with aryl(TMP)io...
Scheme 5: Coupling reaction of arynes generated by iodonium salts 6 and arynophiles 14 for the synthesis of t...
Scheme 6: Metal-free arylation of quinoxalines 17 and quinoxalinones 19 with DAISs 16.
Scheme 7: Transition-metal-free, C–C cross-coupling of 2-naphthols 21 to 1-arylnapthalen-2-ols 22 employing d...
Scheme 8: Arylation of vinyl pinacol boronates 23 to trans-arylvinylboronates 24 in presence of hypervalent i...
Scheme 9: Light-induced selective arylation at C2 of quinoline N-oxides 25 and pyridine N-oxides 28 in the pr...
Scheme 10: Plaussible mechanism for the light-induced selective arylation of N-heterobiaryls.
Scheme 11: Photoinduced arylation of heterocycles 31 with the help of diaryliodonium salts 16 activated throug...
Scheme 12: Arylation of MBH acetates 33 with DIPEA and DAIRs 16.
Scheme 13: Aryl sulfonylation of MBH acetates 33 with DABSO and diphenyliodonium triflates 16.
Scheme 14: Synthesis of oxindoles 37 from N-arylacrylamides 36 and diaryliodonium salts 26.
Scheme 15: Mechanically induced N-arylation of amines 38 using diaryliodonium salts 16.
Scheme 16: o-Fluorinated diaryliodonium salts 40-mediated diarylation of amines 38.
Scheme 17: Proposed mechanism for the diarylation of amines 38 using o-fluorinated diaryliodonium salts 40.
Scheme 18: Ring-opening difunctionalization of aliphatic cyclic amines 41.
Scheme 19: N-Arylation of amino acid esters 44 using hypervalent iodonium salts 45.
Scheme 20: Regioselective N-arylation of triazole derivatives 47 by hypervalent iodonium salts 48.
Scheme 21: Regioselective N-arylation of tetrazole derivatives 50 by hypervalent iodonium salt 51.
Scheme 22: Selective arylation at nitrogen and oxygen of pyridin-2-ones 53 by iodonium salts 16 depending on t...
Scheme 23: N-Arylation using oxygen-bridged acyclic diaryliodonium salt 56.
Scheme 24: The successive C(sp2)–C(sp2)/O–C(sp2) bond formation of naphthols 58.
Scheme 25: Synthesis of diarylethers 62 via in situ generation of hypervalent iodine salts.
Scheme 26: O-Arylated galactosides 64 by reacting protected galactosides 63 with hypervalent iodine salts 16 i...
Scheme 27: Esterification of naproxen methyl ester 65 via formation and reaction of naproxen-containing diaryl...
Scheme 28: Etherification and esterification products 72 through gemfibrozil methyl ester-derived diaryliodoni...
Scheme 29: Synthesis of iodine containing meta-substituted biaryl ethers 74 by reacting phenols 61 and cyclic ...
Scheme 30: Plausible mechanism for the synthesis of meta-functionalized biaryl ethers 74.
Scheme 31: Intramolecular aryl migration of trifluoromethane sulfonate-substituted diaryliodonium salts 75.
Scheme 32: Synthesis of diaryl ethers 80 via site-selective aryl migration.
Scheme 33: Synthesis of O-arylated N-alkoxybenzamides 83 using aryl(trimethoxyphenyl)iodonium salts 82.
Scheme 34: Synthesis of aryl sulfides 85 from thiols 84 using diaryliodonium salts 16 in basic conditions.
Scheme 35: Base-promoted synthesis of diarylsulfoxides 87 via arylation of general sulfinates 86.
Scheme 36: Plausible mechanism for the arylation of sulfinates 86 via sulfenates A to give diaryl sulfoxides 87...
Scheme 37: S-Arylation reactions of aryl or heterocyclic thiols 88.
Scheme 38: Site-selective S-arylation reactions of cysteine thiol groups in 91 and 94 in the presence of diary...
Scheme 39: The selective S-arylation of sulfenamides 97 using diphenyliodonium salts 98.
Scheme 40: Plausible mechanism for the synthesis of sulfilimines 99.
Scheme 41: Synthesis of S-arylxanthates 102 by reacting DAIS 101 with potassium alkyl xanthates 100.
Figure 2: Structured of the 8-membered and 4-membered heterotetramer I and II.
Scheme 42: S-Arylation by diaryliodonium cations 103 using KSCN (104) as a sulfur source.
Scheme 43: S-Arylation of phosphorothioate diesters 107 through the utilization of diaryliodonium salts 108.
Scheme 44: Transfer of the aryl group from the hypervalent iodonium salt 108 to phosphorothioate diester 107.
Scheme 45: Synthesis of diarylselenides 118 via diarylation of selenocyanate 115.
Scheme 46: Light-promoted arylation of tertiary phosphines 119 to quaternary phosphonium salts 121 using diary...
Scheme 47: Arylation of aminophosphorus substrate 122 to synthesize phosphine oxides 123 using aryl(mesityl)io...
Scheme 48: Reaction of diphenyliodonium triflate (16) with DMSO (124) via thia-Sommelet–Hauser rearrangement.
Scheme 49: Synthesis of biaryl compounds 132 by reacting diaryliodonium salts 131 with arylhydroxylamines 130 ...
Scheme 50: Synthesis of substituted indazoles 134 and 135 from N-hydroxyindazoles 133.
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
- , and Parkinson's disease, cardiovascular diseases, inflammation, AIDS and others have their origin in context with the activities of protein kinases, such as glycogen synthase kinase-3 (GSK-3β) and cyclin-dependent kinases (CDK’s). The phosphorylation of the amino acid moieties of several enzymes is
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...
Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines
- Dmitriy Yu. Vandyshev,
- Daria A. Mangusheva,
- Khidmet S. Shikhaliev,
- Kirill A. Scherbakov,
- Oleg N. Burov,
- Alexander D. Zagrebaev,
- Tatiana N. Khmelevskaya,
- Alexey S. Trenin and
- Fedor I. Zubkov
Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236
- include the use of immunosuppressive and cytotoxic drugs, broad-spectrum antibiotic therapy, pre-existing illnesses such as AIDS or diabetes, and the use of central venous catheters, urethral catheters, and implantable medical devices [42]. The mainstay of therapy for these infections is the use of broad
Graphical Abstract
Figure 1: Some biologically active compounds and organic fluorophores containing the imidazo[1,2-a]pyrimidine...
Figure 2: Existing approaches to imidazo[1,2-a]pyrimidines.
Scheme 1: Reaction of 2-aminoimidazole (1) with N-substituted maleimides (2) and N-arylitaconimides (3).
Scheme 2: Plausible synthetic routes for the interaction of N-substituted maleimides 2 with 2-aminoimidazole (...
Scheme 3: Plausible synthetic routes for the interaction of or N-arylitaconimides 3 with 2-aminoimidazole (1)....
Figure 3: Key correlations observed in the NOESY and HMBC spectra of the products 4d and 5d.
Scheme 4: Results of MEP calculations for the reaction of N-phenylmaleimide (2a) with 2-aminoimidazole (1).
Scheme 5: Results of MEP calculations for the reaction of N-phenylithaconimide (3a) with 2-aminoimidazole (1)....
Figure 4: Structures of imidazo[1,2-a]pyrimidines selected for docking and voriconazole selected for comparis...
Figure 5: (A) Position of the (S)-isomer of compound 4e in the active site of CYP51 after molecular dockinga....
Computational design for enantioselective CO2 capture: asymmetric frustrated Lewis pairs in epoxide transformations
- Maxime Ferrer,
- Iñigo Iribarren,
- Tim Renningholtz,
- Ibon Alkorta and
- Cristina Trujillo
Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224
- catalyse reactions following mechanisms 2 or 3 (Figure 5B,C). For each group, an analysis was performed using two volcano plots. The first plot aids in identifying the best families, which are then exclusively considered for the second volcano plot. The second plot helps to determine the most appropriate
Graphical Abstract
Scheme 1: Reaction between propylene oxide (PO) and CO2 and the five catalyst scaffolds under study. The posi...
Figure 1: Schematic representation of an (A) 2D and a (B) 3D volcano plot. The abbreviation “cat.” stands for...
Scheme 2: Capture reactions of CO2 or an epoxide by FLP.
Figure 2: (A) Structure of PO annotated with the C–O bond distances and electron densities at the BCPs. BCPs ...
Figure 3: Symmetric FLP scaffolds considered in the first study. X denotes N or P.
Figure 4: Subset of FLP scaffolds considered in the catalyst optimisation study. Substituents and labels are ...
Figure 5: Coupling reaction between PO and CO2. Depending on the catalyst considered, the reaction follows me...
Figure 6: VOLCANO plot group 1. The free energies of pre-TS01 assembly and Min2 are considered for the correl...
Figure 7: VOLCANO plot group 2. The free energies of pre-TS01 assembly and Min2 are considered for the correl...
Scheme 3: Asymmetric catalysis studied. On the left, the catalyst proposed by Gao et al. for the asymmetric h...
Figure 8: Catalysed reaction between the (S)-enantiomer of propylene oxide and CO2 resulting in the formation...
Figure 9: Schemes of the different asymmetric reactions observed. Hydrogen capable of rotation is marked in o...
Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics
- Luca Julianna Tóth,
- Kateřina Krejčová,
- Milan Dejmek,
- Eva Žilecká,
- Blanka Klepetářová,
- Lenka Poštová Slavětínská,
- Evžen Bouřa and
- Radim Nencka
Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91
- : antivirotics; nonnucleotide inhibitor; RNA-dependent RNA polymerase; SARS-CoV-2; Introduction Epidemics caused by various viral infections, such as AIDS, Zika fever, Dengue fever, or Ebola, are a constant threat to communities of all sizes [1]. The COVID-19 pandemic, caused by the newly emerged severe acute
Graphical Abstract
Figure 1: Structure of HeE1-2Tyr (1) and of the derivatives synthesized in this work.
Scheme 1: Synthetic pathway to benzoxazole analogue 2 of HeE1-2Tyr (1). Reagents and conditions: a) TMSN3, Tf...
Scheme 2: Synthetic pathway to pyridone derivatives 3a–c of HeE1-2Tyr (1). Reagents and conditions: a) MeI, K2...
Scheme 3: Synthetic pathway to thiazolopyridone derivatives 4a,b of HeE1-2Tyr (1). Reagents and conditions: a...
Figure 2: Analysis of inhibitory activity against SARS-CoV-2 RdRp using primer extension assay. A) Gel-based ...
Synthesis and properties of 6-alkynyl-5-aryluracils
- Ruben Manuel Figueira de Abreu,
- Till Brockmann,
- Alexander Villinger,
- Peter Ehlers and
- Peter Langer
Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80
- , including pancreatic, breast, and cervical cancers. Zidovudine is effective against retroviruses and is still used today for the prevention and treatment of HIV/AIDS infections. Brivudine is one of the most potent antiviral agents against herpes zoster virus infections (Figure 1) [17][18][19][20]. Given the
Graphical Abstract
Figure 1: Uracil derivatives in drugs.
Figure 2: Present work as compared to previous studies [25,57-59].
Scheme 1: Synthesis of 1,3-dimethly-5-[2-(aryl)ethynyl]-6-[2-(aryl)ethynyl]uracils 4 and 1,3-dimethyl-5-aryl-...
Scheme 2: Synthesis of 5-bromo-1,3-dimethyl-6-[2-(aryl)ethynyl]uracils 3a–j. Reaction conditions: 2 (1.0 equi...
Scheme 3: Structure of the starting material 2 with its possible mesomeric structures.
Scheme 4: Synthesis of 1,3-dimethyl-5-[2-(aryl)ethynyl]-6-[2-(aryl)ethynyl]uracils 4a–h. Reaction conditions: ...
Scheme 5: Synthesis of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 5a–t. Reaction conditions: 3 (1 equiv),...
Figure 3: ORTEP diagram of 5a front view (a) and side view (b). a) Interactions of the molecules within and b...
Figure 4: UV–vis absorption (left) and emission (right, λex = 400 nm) spectra of 1,3-dimethyl-5-phenyl-6-[2-(...
Synthesis, optical and electrochemical properties of (D–π)2-type and (D–π)2Ph-type fluorescent dyes
- Kosuke Takemura,
- Kazuki Ohira,
- Taiki Higashino,
- Keiichi Imato and
- Yousuke Ooyama
Beilstein J. Org. Chem. 2022, 18, 1047–1054, doi:10.3762/bjoc.18.106
- This work was supported by the Grant-in-Aids for Scientific Research on Innovative Areas “Soft Crystals” (No. 2903) (JSPS KAKENHI Grant No. 18H04520) and the Suga Weathering Technology Foundation.
Graphical Abstract
Scheme 1: Synthesis of OTK-2 and OTT-2.
Figure 1: (a) Photoabsorption and (b) fluorescence (λex = λmax,abs) spectra of OTK-2 [33] and OTT-2 in toluene. (...
Figure 2: Cyclic voltammograms of OTK-2 and OTT-2 (0.1 mM) in DMF containing 0.1 M Bu4NClO4 at a scan rate of...
Figure 3: (a) HOMO and (b) LUMO of OTK-2 [33] and OTT-2 derived from MO calculations (PM5, INDO/S method). The re...
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
- remarkable reduction in deaths related to HIV/AIDS in the United States due to usage of combination drug therapies [26]. In these combination therapies, ʟ-(−)-2’,3’-dideoxy-3’-thiacytidine (1) is one of the standard components, having an enhanced pharmacological profile over AZT and other dideoxynucleotide
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing
- Luke O. Jones,
- Leah Williams,
- Tasmin Boam,
- Martin Kalmet,
- Chidubem Oguike and
- Fiona L. Hatton
Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171
- engineering, cell culture and microbiology, or specific chemicals to aid in chemical, environmental, and medicinal filtration, and purification applications [5][19][42][60][61]. This also aids cell immobilisation, putting cryogels forward for potential use in bioreactors [5][42]. Cells can be included within
Graphical Abstract
Figure 1: Schematic representation of the process of aqueous cryogel formation, using (a) monomers/small mole...
Figure 2: Microarchitecture of gelatin cryogels. (A) Surface and cross-sectional SEM micrographs of highly po...
Figure 3: Principle of 3D-cryogel printing. A) Illustration of 3D-printing of cryogels. B) Illustration of th...
Figure 4: Illustration of the production of the injectable multifunctional composite, comprised of alginate c...
Figure 5: Digital and SEM photographs of PETEGA cryogel at 20 °C (top) and 50 °C (bottom), synthesised via UV...
Figure 6: Cell morphology of T47D breast cancer cells cultured in HA cryogels. (A) Schematic representation o...
Figure 7: Preparation of PDMA/β-CD cryogel via cryogenic treatment and photochemical crosslinking in frozen s...
Figure 8: (A) Healing rate of wounds treated with autoclaved CG11 cryogels and those treated with 70% ethanol...
Figure 9: In vivo haemostatic capacity evaluation of the cryogels. Blood loss (a) and haemostatic time (b) in...
Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus
- Jana M. Boysen,
- Nauman Saeed and
- Falk Hillmann
Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124
- treatment and damage to the cell walls while fumagillin aids in immune evasion by reducing ROS levels, degranulation and actin filamentation in neutrophils [60][132]. In nature, several fungal species are known to produce caspofungin which could trigger fumagillin production in natural environments [132
Graphical Abstract
Figure 1: Schematic overview of fungal interactions in the environment. Fungi can be found in essentially all...
Figure 2: Fungal derived bioactive natural compounds with ecological and/or economic relevance.
Figure 3: Gliotoxin biosynthetic gene cluster and it major biosynthetic transformations: Gliotoxin (5) is the...
Figure 4: Amoebicidal secondary metabolites trypacidin and fumagillin of Aspergillus fumigatus.
Figure 5: Intermediates of the DHN-melanin biosynthesis in Aspergillus fumigatus.
Figure 6: Intermediates and products of the fumigaclavine C biosynthesis.
Figure 7: Bioactive secondary metabolites of Aspergillus fumigatus.
Figure 8: Helvolic acid gene cluster of A. fumigatus.
Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs
- Jongwoo Son
Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122
- constitute an important structural modality in small-molecule drugs, such as levonorgestrel (birth control drug), efavirenz (HIV/AIDS treatment), and erlotinib (anticancer). Although step-economical C–H alkynylations have been investigated with 4d and 5d transition metals, 3d metal-catalyzed late-stage C–H
Graphical Abstract
Scheme 1: Mn-catalyzed late-stage fluorination of sclareolide (1) and complex steroid 3.
Figure 1: Proposed reaction mechanism of C–H fluorination by a manganese porphyrin catalyst.
Scheme 2: Late-stage radiofluorination of biologically active complex molecules.
Figure 2: Proposed mechanism of C–H radiofluorination.
Scheme 3: Late-stage C–H azidation of bioactive molecules. a1.5 mol % of Mn(TMP)Cl (5) was used. bMethyl acet...
Figure 3: Proposed reaction mechanism of manganese-catalyzed C–H azidation.
Scheme 4: Mn-catalyzed late-stage C–H azidation of bioactive molecules via electrophotocatalysis. a2.5 mol % ...
Figure 4: Proposed reaction mechanism of electrophotocatalytic azidation.
Scheme 5: Manganaelectro-catalyzed late-stage azidation of bioactive molecules.
Figure 5: Proposed reaction pathway of manganaelectro-catalyzed late-stage C–H azidation.
Scheme 6: Mn-catalyzed late-stage amination of bioactive molecules. a3 Å MS were used. Protonation with HBF4⋅...
Figure 6: Proposed mechanism of manganese-catalyzed C–H amination.
Scheme 7: Mn-catalyzed C–H methylation of heterocyclic scaffolds commonly found in small-molecule drugs. aDAS...
Scheme 8: Examples of late-stage C–H methylation of bioactive molecules. aDAST activation. bFor insoluble sub...
Scheme 9: A) Mn-catalyzed late-stage C–H alkynylation of peptides. B) Intramolecular late-stage alkynylative ...
Figure 7: Proposed reaction mechanism of Mn(I)-catalyzed C–H alkynylation.
Scheme 10: Late-stage Mn-catalyzed C–H allylation of peptides and bioactive motifs.
Scheme 11: Intramolecular C–H allylative cyclic peptide formation.
Scheme 12: Late-stage C–H glycosylation of tryptophan analogues.
Scheme 13: Late-stage C–H glycosylation of tryptophan-containing peptides.
Scheme 14: Late-stage C–H alkenylation of tryptophan-containing peptides.
Scheme 15: A) Late-stage C–H macrocyclization of tryptophan-containing peptides and B) traceless removal of py...
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
- Nikita Brodyagin,
- Martins Katkevics,
- Venubabu Kotikam,
- Christopher A. Ryan and
- Eriks Rozners
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
Graphical Abstract
Figure 1: Structure of DNA and PNA.
Figure 2: PNA binding modes: (A) PNA–dsDNA 1:1 triplex; (B) PNA–DNA–PNA strand-invasion triplex; (C) the Hoog...
Figure 3: Structure of P-form PNA–DNA–PNA triplex from reference [41]. (A) view in the major groove and (B) view ...
Figure 4: Structures of backbone-modified PNA.
Figure 5: Structures of PNA having α- and γ-substituted backbones.
Figure 6: Structures of modified nucleobases in PNA to improve Hoogsteen hydrogen bonding to guanine and aden...
Figure 7: Proposed hydrogen bonding schemes for modified PNA nucleobases designed to recognize pyrimidines or...
Figure 8: Modified nucleobases to modulate Watson–Crick base pairing and chemically reactive crosslinking PNA...
Figure 9: Examples of triplets formed by Janus-wedge PNA nucleobases (blue). R1 denotes DNA, RNA, or PNA back...
Figure 10: Examples of fluorescent PNA nucleobases. R1 denotes DNA, RNA, or PNA backbones.
Figure 11: Endosomal entrapment and escape pathways of PNA and PNA conjugates.
Figure 12: (A) representative cell-penetrating peptides (CPPs), (B) conjugation designs and linker chemistries....
Figure 13: Proposed delivery mode by pHLIP-PNA conjugates (A) the transmembrane section of pHLIP interacting w...
Figure 14: Structures of modified penetratin CPP conjugates with PNA linked through either disulfide (for stud...
Figure 15: Chemical structure of C9–PNA, a stable amphipathic (cyclic-peptide)–PNA conjugate.
Figure 16: Structures of PNA conjugates with a lipophilic triphenylphosphonium cation (TPP–PNA) through (A) th...
Figure 17: Structures of (A) chloesteryl–PNA, (B) cholate–PNA and (C) cholate–PNA(cholate)3.
Figure 18: Structures of PNA–GalNAc conjugates (A) (GalNAc)2K, (B) triantennary (GalNAc)3, and (C) trivalent (...
Figure 19: Vitamin B12–PNA conjugates with different linkages.
Figure 20: Structures of (A) neomycin B, (B) PNA–neamine conjugate, and (C) PNA–neosamine conjugate.
Figure 21: PNA clamp (red) binding to target DNA containing a mixture of sequences (A) PNA binds with higher a...
Figure 22: Rolling circle amplification using PNA openers (red) to invade a dsDNA target forming a P-loop. A p...
Figure 23: Molecular beacons containing generic fluorophores (Fl) and quenchers (Q) recognizing a complementar...
Figure 24: (A) Light-up fluorophores such as thiazole orange display fluorescence enhancement upon binding to ...
Figure 25: Templated fluorogenic detection of oligonucleotides using two PNAs. (A) Templated FRET depends on h...
Figure 26: Lateral flow devices use a streptavidin labeled strip on nitrocellulose paper to anchor a capture P...
Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides
- Roslyn M. Ray,
- Anders Højgaard Hansen,
- Maria Taskova,
- Bernhard Jandl,
- Jonas Hansen,
- Citra Soemardy,
- Kevin V. Morris and
- Kira Astakhova
Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75
- acquired through the NIH AIDS reagent program and were engineered to express high levels of the HIV-1 coreceptor CCR5 [44]. HEK293T-gp160 cells were a kind gift from Dr. Bing Chen (Harvard, MA), and stably expressed the 92UG037.8 strain of the viral envelope protein, Env [45]. The human brain endothelial
Graphical Abstract
Figure 1: Components of the LNPs. A) Lipid species and lipidated cell-penetrating peptides applied by postins...
Figure 2: LNPs with T7 pass through the transwell cell barrier and are taken up by target cells. HeLa (CCR5-n...
Figure 3: LNPs with Tat pass through the transwell cell barrier and are taken up by target cells. A) Percenta...
Figure 4: LNPs do not stimulate secretion of proinflammatory cytokines. A) GMCSF-primed MDMs were treated wit...
Figure 5: LNPs modestly affect cell viability in a cell-specific manner. HeLa (A) or HEK293T cells (B) were t...
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
- between benzimidazole-linked aminopyridine and Lewis acid activated aldehyde which further on nucleophilic addition with substituted isocyanide leads to intermediate B. A 5-exo-dig intramolecular cyclization with isocyanide aids in the formation of the imidazo[1,2-a]pyridine intermediate C. The final
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.
Molecular basis for protein–protein interactions
- Brandon Charles Seychell and
- Tobias Beck
Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1
- that a nucleic acid scaffold aids the assembly by concentrating assembly units and providing additional association energy. Some viral capsids can self-assemble around other scaffolds that mimic the viral genome in charge and size [89] or can also assemble without any scaffold to form empty capsid
Graphical Abstract
Figure 1: Different methodologies employed to study PPIs. The protein used for illustration is the heterodime...
Figure 2: Mechanisms of homooligomeric complex formations. a) Domain swapping of RNase A (PDB: 1A2W) [73]. The sw...
Figure 3: Parts a) and b) represent the electron densities and B-factors of TMV, respectively. The cryo-EM st...
Figure 4: Schematic of the general assembly of charged protein containers to form binary nanoparticle superla...
Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification
- Steffen Lippold,
- Arnoud H. de Ru,
- Jan Nouta,
- Peter A. van Veelen,
- Magnus Palmblad,
- Manfred Wuhrer and
- Noortje de Haan
Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253
- glycoforms as well as modifications of the glycopeptides and aids the optimization of the search space for MS/MS annotation in an iterative manner. Although an MS1-based approach alone allows the identification of more unique glycopeptides as compared to an MS/MS-based approach, a combined workflow is
Graphical Abstract
Figure 1: Integration of automated glycopeptide identification by Byonic and GlycopeptideGraphMS (aided by Op...
Figure 2: Representative IgG and IgA glycopeptide clusters detected by GlycopeptideGraphMS.
Figure 3: Representative GlycopeptideGraphMS output for peptides of interest. Assigned compositions were iden...
Figure 4: Comparison of quantification results obtained by manual integration of EICs in Skyline (black), aut...
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
- they have been used to serve as scaffolds for the assembly of protein arrays and crystallization aids [23][24][25][26][27][28]. In addition, a terbiumIII complex termed crystallophore has been developed as a crystallographic nucleation and phasing tool for protein crystallography that can also easily
- larger ordered structures makes especially the larger calixarenes potent “molecular glues” and crystallization aids [23][24][25][26][27][28]. The PAF protein for example did not yield diffracting crystals on its own, but good quality crystals were obtained in the presence of all calix[n]arenes [25]. The
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...
Architecture and synthesis of P,N-heterocyclic phosphine ligands
- Wisdom A. Munzeiwa,
- Bernard Omondi and
- Vincent O. Nyamori
Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35
- N- and/or O-donor atoms [44]. During catalysis the weakly coordinating hard donor atom detaches to give way for the incoming substrate to coordinate to the metal center [45]. This behavior also aids in ligands being able to stabilize low-valent metal states and promote oxidative addition reactions
Graphical Abstract
Scheme 1: Synthesis of pyridylphosphine ligands.
Figure 1: Pyridylphosphine ligands.
Scheme 2: Synthesis of piperidyl- and oxazinylphosphine ligands.
Scheme 3: Synthesis of linear multi-chelate pyridylphosphine ligands.
Scheme 4: Synthesis of chiral acetal pyridylphosphine ligands.
Scheme 5: Synthesis of diphenylphosphine-substituted triazine ligands.
Scheme 6: Synthesis of (pyridine-2-ylmethyl)phosphine ligands.
Scheme 7: Synthesis of diphosphine pyrrole ligands.
Scheme 8: Synthesis of 4,5-diazafluorenylphosphine ligands.
Scheme 9: Synthesis of thioether-containing pyridyldiphosphine ligands starting from ethylene sulfide and dip...
Scheme 10: Synthesis of monoterpene-derived phosphine pyridine ligands.
Scheme 11: Synthesis of N-phenylphosphine-substituted imidazole ligands.
Scheme 12: Synthesis of triazol-4-ylphosphine ligands.
Scheme 13: Synthesis of phosphanyltriazolopyridines and product selectivity depending on the substituents’ eff...
Scheme 14: Synthesis of PTA-phosphine ligands.
Scheme 15: Synthesis of isomeric phosphine dipyrazole ligands by varying the reaction temperature.
Scheme 16: Synthesis of N-tethered phosphine imidazolium ligands (route A) and diphosphine imidazolium ligands...
Scheme 17: Synthesis of {1-[2-(pyridin-2-yl)- (R = CH) and {1-[2-(pyrazin-2-yl)quinazolin-4-yl]naphthalen-2-yl...
Scheme 18: Synthesis of oxazolylindolylphosphine ligands 102.
Scheme 19: Synthesis of pyrrolylphosphine ligands.
Scheme 20: Synthesis of phosphine guanidinium ligands.
Scheme 21: Synthesis of a polydentate aminophosphine ligand.
Scheme 22: Synthesis of quinolylphosphine ligands.
Scheme 23: Synthesis of N-(triazolylmethyl)phosphanamine ligands.
Figure 2: Triazolylphosphanamine ligands synthesized by Wassenaar’s method [22].
Scheme 24: Synthesis of oxazaphosphorines.
Scheme 25: Synthesis of paracyclophane pyridylphosphine ligands.
Scheme 26: Synthesis of triazolylphosphine ligands.
Figure 3: Click-phosphine ligands.
Scheme 27: Ferrocenyl pyridylphosphine imine ligands.
Scheme 28: Synthesis of phosphinooxazolines (PHOX).
Scheme 29: Synthesis of ferrocenylphosphine oxazoles.
A chemically contiguous hapten approach for a heroin–fentanyl vaccine
- Yoshihiro Natori,
- Candy S. Hwang,
- Lucy Lin,
- Lauren C. Smith,
- Bin Zhou and
- Kim D. Janda
Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100
- States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks
Graphical Abstract
Figure 1: Graphical summary of chemically contiguous opioid vaccine approach. A) Illustration of chemically c...
Figure 2: The chemically contiguous heroin–fentanyl haptens designed in this study. Grouping was based on the...
Figure 3: Heroin intermediates used to synthesize HF-1 through HF-9.
Scheme 1: General outline of HF-1, HF-2, HF-3, HF-7 synthesis from fentanyl intermediate 5 and heroin interme...
Scheme 2: Synthesis of fentanyl intermediate 5. Reaction conditions: a) phthalic anhydride, AcOH, reflux, 81%...
Scheme 3: General outline of HF-5, HF-8, HF-9 synthesis from fentanyl intermediates 28 and 46, and heroin int...
Scheme 4: Parallel synthesis of fentanyl domains 25 and 34, for HF-4 and HF-6, respectively.
Scheme 5: General strategy and coupling partners for the chemically contiguous series. aGeneral conditions fo...
Figure 4: Vaccination, titer assessment, and bleed schedule.
Figure 5: Summary of behavioral data for most promising chemically contiguous vaccine HF-7, compared to singu...
Figure 6: Summary of behavioral data for phenethyl-linked haptens HF-4 and HF-6. Bars represent mean ± SEM.
Figure 7: Correlation plots of dual hapten vaccines comparing week 5 and 8 ELISA midpoint titers to ED50 valu...
On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site
- Eirinaios I. Vrettos,
- Gábor Mező and
- Andreas G. Tzakos
Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80
- most common anticancer agents used against a wide variety of tumors. It is sold under the brand name Taxol by Bristol-Myers Squibb Company and is FDA approved for the treatment of breast cancer, ovarian cancer, non-small cell lung cancer and AIDS-related Kaposi's sarcoma. The main disadvantages in the
Graphical Abstract
Figure 1: Conventional chemotherapy versus targeted chemotherapy. Black color = Solid malignant tumor; red = ...
Figure 2: A. General structural architecture of the ideal navigated drug delivery system [31]. B. General structu...
Figure 3: Binding and penetration mechanism of iRGD. The iRGD peptide is accumulated on the surface of αv int...
Figure 4: Representative examples of anticancer drugs utilized for the construction of PDCs. The most usual c...
Figure 5: Illustration of the drug release mechanism from the self-immolative spacer PABC conjugated to a tum...
Figure 6: Structures of the PDCs named AN-152 and AN-207.
Figure 7: Structure of the PDC named AN-238.
Figure 8: Chemical structure and synthetic scheme for the PDC ANG1005. (A) ANG1005 is composed of three molec...
Figure 9: Structure of oxime linked Dau–GnRH-III conjugate with or without cathepsin B labile spacer and thei...
Figure 10: Synthesis of the most effective GnRH-III–Dau conjugate with two drug molecules [153].
Figure 11: Structures of the four different PDCs of D-Lys6-GnRH-I and gemcitabine (GSG, GSG2, 3G, 3G2) [19].
Figure 12: Structures of (A) native sunitinib; (B) SAN1 analog of sunitinib and (C) assembled PDC named SAN1GS...
Figure 13: Synthetic scheme for the formation of GSG and the unexpected side product [156].
Figure 14: Illustration of uncharted guanidinium peptide coupling reagent side reactions during PDCs synthesis ...
Figure 15: Putative mechanism for the formation of the uronium side product [156].
D–A–D-type orange-light emitting thermally activated delayed fluorescence (TADF) materials based on a fluorenone unit: simulation, photoluminescence and electroluminescence studies
- Lin Gan,
- Xianglong Li,
- Xinyi Cai,
- Kunkun Liu,
- Wei Li and
- Shi-Jian Su
Beilstein J. Org. Chem. 2018, 14, 672–681, doi:10.3762/bjoc.14.55
- is a promising acceptor for orange TADF materials, which aids in the design of the TADF behavior and luminescence color of 1 and 2. Owing to the strong electron-withdrawing ability and extended conjugation length of fluorenone unit, the emission peaks of both materials show obvious red-shifts from
Graphical Abstract
Scheme 1: Molecular structures of isomers 1 and 2.
Figure 1: (a) The optimized S0 geometries of 1 (left) and 2 (right) on B3LYP/6-31G* level in gas phase; (b) T...
Figure 2: UV–vis (solid point) and photoluminescence (hollow point) spectra of 1 and 2 in dilute solution.
Figure 3: The low temperature photoluminescence spectra of 1 (left) and 2 (right) in toluene at 77 K.
Figure 4: (a) Time-resolved transient photoluminescence decay spectra of the doped films (8 wt % in CBP) meas...
Figure 5: Energy level (eV) diagrams of OLED devices and the chemical structures of the materials utilized fo...
Figure 6: J–V–L (current density–voltage–luminance) (left) and EQE–current density characteristics of the dev...
Figure 7: EQE–current density characteristics of the devices based on 1 (top) and 2 (bottom). The solid lines...
Computational methods in drug discovery
- Sumudu P. Leelananda and
- Steffen Lindert
Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267
- ) protease is a prime drug target for anti-AIDS therapeutics. In the early 1990s many approved HIV protease inhibitors were developed to target HIV infections using structure-based molecular docking. It was a ground breaking success at that time and made it possible for HIV infected individuals to live
Graphical Abstract
Figure 1: Schematic representation of a computer-aided drug discovery (CADD) pipeline. CADD methods are broad...
Figure 2: FDA approved drugs Saquinavir and Amprenavir for the treatment of HIV infections. (a) The structure...
Figure 3: (a) The crystal structure showing the binding of Dorzolamide (orange) to carbonic anhydrase II (pur...
Figure 4: The best ligand binding site identified by SiteHound in HIV-1 protease. The ligand binding pocket i...
Figure 5: Binding mode prediction. The known inhibitor Dorzolamide is docked into Carbonic anhydrase II cryst...
Figure 6: The molecular structure of Raltegravir. Raltegravir is an FDA approved drug used in the treatment o...
Figure 7: An example alchemical thermodynamic cycle for a protein–ligand binding free energy calculation. The...
Figure 8: Schematic diagram showing the steps involved in QSAR. Known drug molecule activity and descriptor d...
Figure 9: A few drugs discovered with the help of ligand-based drug discovery tools. (a) Zolmitriptan: used a...
Interactions between cyclodextrins and cellular components: Towards greener medical applications?
- Loïc Leclercq
Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261
Graphical Abstract
Scheme 1: Structure and conventional representation of native CDs.
Scheme 2: Proposed mechanism for morphological changes in erythrocytes induced by methylated CDs.
Scheme 3: Proposed mechanism for the conformational change of egg white lysozyme with temperature elevating i...
Scheme 4: Sugar hydrophobicity scale according to Janado and Yano and correlation with the binding constant v...
Scheme 5: Principle of chemically switched DNA intercalators based on anthryl(alkylamino)-β-CD/1-adamantanol ...
Scheme 6: Normal (left) and diseased artery (right).
Scheme 7: Kinetics of [DiC10] insertion into the viral envelope without (left) or with γ-CD (right). Note tha...
Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates
- Maurizio Selva,
- Alvise Perosa,
- Sandro Guidi and
- Lisa Cattelan
Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181
- 10 minutes), and, most importantly, higher GD selectivity (63% compared to 45% after 30 minutes) under the same reaction conditions. In order to explain such a behavior, a cooperative mechanism for the ionic liquid catalysis was invoked, whereby the electrophilic nitrogen atom aids in activating the
Graphical Abstract
Scheme 1: The transesterification of diethyl oxalate (DEO) with phenol catalyzed by MoO3/SiO2.
Scheme 2: Transesterification of a triglyceride (TG) with DMC for biodiesel production using KOH as the base ...
Scheme 3: Top: Green methylation of phosphines and amines by dimethyl carbonate (Q = N, P). Bottom: anion met...
Figure 1: Structures of some representative SILs and PILs systems. MCF is a silica-based mesostructured mater...
Scheme 4: Synthesis of the acid polymeric IL. EGDMA: ethylene glycol dimethacrylate.
Scheme 5: The transesterification of sec-butyl acetate with MeOH catalyzed by some acidic imidazolium ILs.
Figure 2: Representative examples of ionic liquids for biodiesel production.
Scheme 6: Top: phosgenation of methanol; middle: EniChem and Ube processes; bottom: Asahi process for the pro...
Scheme 7: The transesterification in the synthesis of organic carbonates.
Scheme 8: The transesterification of DMC with alcohols and diols.
Scheme 9: Transesterification of glycerol with DMC in the presence of 1-n-butyl-3-methylimidazolium-2-carboxy...
Scheme 10: Synthesis of the BMIM-2-CO2 catalyst from butylimidazole and DMC.
Scheme 11: Plausible cooperative (nucleophilic–electrophilic) mechanism for the transesterification of glycero...
Scheme 12: Synthesis of diazabicyclo[5.4.0]undec-7-ene-based ionic liquids.
Scheme 13: Synthesis of the DABCO–DMC ionic liquid.
Scheme 14: Cooperative mechanism of ionic liquid-catalyzed glycidol production.
Scheme 15: [TMA][OH]-catalyzed synthesis of glycidol (GD) from glycerol and dimethyl carbonate [46].
Scheme 16: [BMIM]OH-catalyzed synthesis of DPC from DMC and 1-pentanol.
Figure 3: Representative examples of ionic liquids for biodiesel production.
Figure 4: Acyclic non-symmetrical organic carbonates synthetized with 1-(trimethoxysilyl)propyl-3-methylimida...
Scheme 17: A simplified reaction mechanism for DMC production.
Scheme 18: [P8881][MeOCO2] metathesis with acetic acid and phenol.
Figure 5: Examples of carbonates obtained through transesterification using phosphonium salts as catalysts.
Scheme 19: Examples of carbonates obtained from different bio-based diols using [P8881][CH3OCO2] as catalyst.
Scheme 20: Ambiphilic catalysis for transesterification reactions in the presence of carbonate phosphonium sal...
Opportunities and challenges for direct C–H functionalization of piperazines
- Zhishi Ye,
- Kristen E. Gettys and
- Mingji Dai
Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70
- used to treat HIV/AIDS [5]. Gatifloxacin is an important fluoroquinolone antibiotic [6]. Despite the high frequency appearance of piperazines in small-molecule pharmaceuticals, over 80% only contain substituents at the two nitrogen atoms and a very small fraction of them have simple carbon
Graphical Abstract
Figure 1: Selected piperazine-containing small-molecule pharmaceuticals.
Figure 2: Strategies for the synthesis of carbon-substituted piperazines.
Figure 3: The first α-lithiation of N-Boc-protected piperazines by van Maarseveen et al. in 2005 [37].
Figure 4: α-Lithiation of N-Boc-N’-tert-butyl piperazines by Coldham et al. in 2010 [38].
Figure 5: Diamine-free α-lithiation of N-Boc-piperazines by O’Brien, Campos, et al. in 2010 [40].
Figure 6: The first enantioselective α-lithiation of N-Boc-piperazines by McDermott et al. in 2008 [41].
Figure 7: Dynamic thermodynamic resolution of lithiated of N-Boc-piperazines by Coldham et al. in 2010 [38].
Figure 8: Enantioselective α-lithiation of N-Boc-N’-alkylpiperazines by O’Brien et al. in 2013 and 2016 [42,43].
Figure 9: Asymmetric α-functionalization of N-Boc-piperazines with Ph2CO by O’Brien et al. in 2016 [43].
Figure 10: A “chiral auxiliary” strategy toward enantiopure α-functionalized piperazines by O’Brien et al. 201...
Figure 11: Installation of methyl group at the α-position of piperazines by O’Brien et al. 2016 [43].
Figure 12: α-Lithiation trapping of C-substituted N-Boc-piperazines by O’Brien et al. 2016 [43].
Figure 13: Rh-catalyzed reactions of N-(2-pyridinyl)piperazines by Murai et al. in 1997 [52].
Figure 14: Ta-catalyzed hydroaminoalkylation of piperazines by Schafer et al. in 2013 [55].
Figure 15: Photoredox catalysis for α-C–H functionalization of piperazines by MacMillan et al. in 2011 and 201...
Figure 16: Copper-catalyzed aerobic C–H oxidation of piperazines by Touré, Sames, et al. in 2013 [67].
Figure 17: Free radical approach by Undheim et al. in 1994 [68].
Figure 18: Anodic oxidation approach by Nyberg et al. in 1976 [70].
