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Search for "complexity" in Full Text gives 388 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide
- Marios Zingiridis,
- Danae Papachristodoulou,
- Despoina Menegaki,
- Konstantinos G. Froudas and
- Constantinos G. Neochoritis
Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13
- convergent chemistry characterized by diversity, complexity and efficiency. MCRs are compatible with C1 chemistry due to the generally great tolerance of different functional groups. They have been mostly employed in the synthesis of oxazolidinones and oxazinanones utilizing CO2 and CO [4][16][17][18][19][20
- anthranilic acid and B) access to heteroannulated pyrimidones by MCRs of suitably substituted heterocycles and formamide as C1 source. Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Diversity and complexity were the essential features of our library of starting
Graphical Abstract
Figure 1: Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged p...
Scheme 1: Strategies towards targeted adducts: A) Niementowski quinazoline synthesis utilizing anthranilic ac...
Scheme 2: Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Divers...
Scheme 3: Synthesis of N-substituted thienopyrimidones 5a–e by a Gewald three-component reaction employing 2-...
Scheme 4: Synthesis of N-substituted quinolinopyrimidones 6a–e from 2-aminoindoles 3a–e and formamide as C1 s...
Scheme 5: Synthesis of N-substituted indolopyrimidones 7a–e from 2-aminoindoles 4a–e and formamide as C1 sour...
Figure 2: Representative fluorescence spectrum of compounds 5b (λex = 330 nm) and 6e (λex = 430 nm) at 0.2 M ...
Figure 3: Molecular geometry observed within the crystal structure of compound 7b (CCDC 2376493).
Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization
- Wentao Yu,
- Zhiyao Yang,
- Chengkan Yu,
- Xiaowei Li and
- Lihua Yuan
Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10
- noncovalent bonding interactions. It also confers on supramolecular assemblies with higher complexity and multilevel ordering [9][10][11], leading to a vast number of applications, for example, for use in detection and separation [12], sensing [13], photocatalysis [14], release [15], and as thermochromic and
Graphical Abstract
Scheme 1: a) Chemical structures of H-bonded macrocycles H1, H2, and guest G1, and schematic representation o...
Figure 1: ESIMS spectrum of an equimolar mixture of G1 and H1 in CHCl3/CH3CN (1:1, v/v), including calculated...
Figure 2: Stacked 1H NMR spectra (CDCl3/CD3CN 1:1, v/v, 400 MHz, 298 K) of G1 upon addition of different equi...
Figure 3: Single-crystal X-ray structure of the complex H2 ⊃ G1. a) Dimeric structure formed by cyclo[6]arami...
Figure 4: Stacked 1H NMR spectra (CDCl3/CD3CN 1:1, v/v, 400 MHz, 298 K) of G2 upon addition of different equi...
Figure 5: TEM images of a solution of H1, G2, and Zn(ClO4)2 at different concentrations (CHCl3/CH3CN 1:1, v/v...
Figure 6: Stacked 1H NMR spectra (CDCl3/CD3CN 1:1, v/v, 400 MHz, 298 K) of G2 and Zn2+ upon addition of diffe...
Figure 7: Specific viscosity of the linear supramolecular polymer in CHCl3/CH3CN (1:1, v/v, 298 K) at variabl...
Figure 8: Variable-concentration 1H NMR spectra of the supramolecular polymer: (a) 2.0 mM, (b) 4.0 mM, (c) 6....
Recent advances in organocatalytic atroposelective reactions
- Henrich Szabados and
- Radovan Šebesta
Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6
Graphical Abstract
Scheme 1: Formation of axially chiral styrenes 3 via iminium activation.
Scheme 2: Synthesis of axially chiral 2-arylquinolines 6.
Scheme 3: Atroposelective intramolecular (4 + 2) annulation leading to aryl-substituted indolines.
Scheme 4: Atroposelective formation of biaryl via twofold aldol condensation.
Scheme 5: Strategy towards diastereodivergent formation of axially chiral oligonaphthylenes.
Scheme 6: Atroposelective formation of chiral biaryls based on a Michael/Henry domino reaction.
Scheme 7: Organocatalytic Michael/aldol cascade followed by oxidative aromatization.
Scheme 8: Atroposelective formation of C(sp2)–C(sp3) axially chiral compounds.
Scheme 9: NHC-catalyzed synthesis of axially chiral styrenes 26.
Scheme 10: NHC-catalyzed synthesis of biaxial chiral pyranones.
Scheme 11: Formation of bridged biaryls with eight-membered lactones.
Scheme 12: The NHC-catalyzed (3 + 2) annulation of urazoles 37 and ynals 36.
Scheme 13: NHC-catalyzed synthesis of axially chiral 4‑aryl α‑carbolines 41.
Scheme 14: NHC-catalyzed construction of N–N-axially chiral pyrroles and indoles.
Scheme 15: NHC-catalyzed oxidative Michael–aldol cascade.
Scheme 16: NHC-catalyzed (4 + 2) annulation for the synthesis of benzothiophene-fused biaryls.
Scheme 17: NHC-catalyzed desymmetrization of N-aryl maleimides.
Scheme 18: NHC-catalyzed deracemization of biaryl hydroxy aldehydes 55a–k into axially chiral benzonitriles 56a...
Scheme 19: NHC-catalyzed desymmetrization of 2-aryloxyisophthalaldehydes.
Scheme 20: NHC-catalyzed DKR of 2-arylbenzaldehydes 62.
Scheme 21: Atroposelective biaryl amination.
Scheme 22: CPA-catalyzed atroposelective amination of 2-anilinonaphthalenes.
Scheme 23: Atroposelective DKR of naphthylindoles.
Scheme 24: CPA-catalyzed kinetic resolution of binaphthylamines.
Scheme 25: Atroposelective amination of aromatic amines with diazodicarboxylates.
Scheme 26: Atroposelective Friedländer heteroannulation.
Scheme 27: CPA-catalyzed formation of axially chiral 4-arylquinolines.
Scheme 28: CPA-catalyzed Friedländer reaction of arylketones with cyclohexanones.
Scheme 29: CPA-catalyzed atroposelective Povarov reaction.
Scheme 30: Atroposelective CPA-catalyzed Povarov reaction.
Scheme 31: Paal–Knorr formation of axially chiral N-pyrrolylindoles and N-pyrrolylpyrroles.
Scheme 32: Atroposelective Paal–Knorr reaction leading to N-pyrrolylpyrroles.
Scheme 33: Atroposelective Pictet–Spengler reaction of N-arylindoles with aldehydes.
Scheme 34: Atroposelective Pictet–Spengler reaction leading to tetrahydroisoquinolin-8-ylanilines.
Scheme 35: Atroposelective formation of arylindoles.
Scheme 36: CPA-catalyzed arylation of naphthoquinones with indolizines.
Scheme 37: Atroposelective reaction of o-naphthoquinones.
Scheme 38: CPA-catalyzed formation of axially chiral arylquinones.
Scheme 39: CPA-catalyzed axially chiral N-arylquinones.
Scheme 40: Atroposelective additions of bisindoles to isatin-based 3-indolylmethanols.
Scheme 41: CPA-catalyzed synthesis of axially chiral arylindolylindolinones.
Scheme 42: CPA-catalyzed reaction between bisindoles and ninhydrin-derived 3-indoylmethanols.
Scheme 43: Atroposelective reaction of bisindoles and isatin-derived imines.
Scheme 44: CPA-catalyzed formation of axially chiral bisindoles.
Scheme 45: Atroposelective reaction of 2-naphthols with alkynylhydroxyisoindolinones.
Scheme 46: CPA-catalyzed reaction of indolylnaphthols with propargylic alcohols.
Scheme 47: Atroposelective formation of indolylpyrroloindoles.
Scheme 48: Atroposelective reaction of indolylnaphthalenes with alkynylnaphthols.
Scheme 49: CPA-catalyzed addition of naphthols to alkynyl-2-naphthols and 2-naphthylamines.
Scheme 50: CPA-catalyzed formation of axially chiral aryl-alkene-indoles.
Scheme 51: CPA-catalyzed formation of axially chiral styrenes.
Scheme 52: Atroposelective formation of alkenylindoles.
Scheme 53: Atroposelective formation of axially chiral arylquinolines.
Scheme 54: Atroposelective (3 + 2) cycloaddition of alkynylindoles with azonaphthalenes.
Scheme 55: CPA-catalyzed formation of axially chiral 3-(1H-benzo[d]imidazol-2-yl)quinolines.
Scheme 56: Atroposelective cyclization of 3-(arylethynyl)-1H-indoles.
Scheme 57: Atroposelective three-component heteroannulation.
Scheme 58: CPA-catalyzed formation of arylbenzimidazols.
Scheme 59: CPA-catalyzed reaction of N-naphthylglycine esters with nitrosobenzenes.
Scheme 60: CPA-catalyzed formation of axially chiral N-arylbenzimidazoles.
Scheme 61: CPA-catalyzed formation of axially chiral arylbenzoindoles.
Scheme 62: CPA-catalyzed formation of pyrrolylnaphthalenes.
Scheme 63: CPA-catalyzed addition of naphthols and indoles to nitronaphthalenes.
Scheme 64: Atroposelective reaction of heterobiaryl aldehydes and aminobenzamides.
Scheme 65: Atroposelective cyclization forming N-arylquinolones.
Scheme 66: Atroposelective formation of 9H-carbazol-9-ylnaphthalenes and 1H-indol-1-ylnaphthalene.
Scheme 67: CPA-catalyzed formation of pyrazolylnaphthalenes.
Scheme 68: Atroposelective addition of diazodicarboxamides to azaborinephenols.
Scheme 69: Catalytic formation of axially chiral arylpyrroles.
Scheme 70: Atroposelective coupling of 1-azonaphthalenes with 2-naphthols.
Scheme 71: CPA-catalyzed formation of axially chiral oxindole-based styrenes.
Scheme 72: Atroposelective electrophilic bromination of aminonaphthoquinones.
Scheme 73: Atroposelective bromination of dienes.
Scheme 74: CPA-catalyzed formation of axially chiral 5-arylpyrimidines.
Scheme 75: Atroposelective hydrolysis of biaryloxazepines.
Scheme 76: Atroposelective opening of dinaphthosiloles.
Scheme 77: Atroposelective reduction of naphthylenals.
Scheme 78: Atroposelective allylic substitution with 2-naphthols.
Scheme 79: Atroposelective allylic alkylation with phosphinamides.
Scheme 80: Atroposelective allylic substitution with aminopyrroles.
Scheme 81: Atroposelective allylic substitution with aromatic sulfinamides.
Scheme 82: Atroposelective sulfonylation of naphthylynones.
Scheme 83: Squaramide-catalyzed reaction of alkynyl-2-naphthols with 5H-oxazolones.
Scheme 84: Formation of axially chiral styrenes via sulfonylative opening of cyclopropanols.
Scheme 85: Atroposelective organo-photocatalyzed sulfonylation of alkynyl-2-naphthols.
Scheme 86: Thiourea-catalyzed atroposelective cyclization of alkynylnaphthols.
Scheme 87: Squaramide-catalyzed formation of axially chiral naphthylisothiazoles.
Scheme 88: Atroposelective iodo-cyclization catalyzed by squaramide C69.
Scheme 89: Squaramide-catalyzed formation of axially chiral oligoarenes.
Scheme 90: Atroposelective ring-opening of cyclic N-sulfonylamides.
Scheme 91: Thiourea-catalyzed kinetic resolution of naphthylpyrroles.
Scheme 92: Atroposelective ring-opening of arylindole lactams.
Scheme 93: Atroposelective reaction of 1-naphthyl-2-tetralones and diarylphosphine oxides.
Scheme 94: Atroposelective reaction of iminoquinones with indoles.
Scheme 95: Kinetic resolution of binaphthylalcohols.
Scheme 96: DKR of hydroxynaphthylamides.
Scheme 97: Atroposelective N-alkylation with phase-transfer catalyst C75.
Scheme 98: Atroposelective allylic substitution via kinetic resolution of biarylsulfonamides.
Scheme 99: Atroposelective bromo-functionalization of alkynylarenes.
Scheme 100: Sulfenylation-induced atroposelective cyclization.
Scheme 101: Atroposelective O-sulfonylation of isochromenone-indoles.
Scheme 102: NHC-catalyzed atroposelective N-acylation of anilines.
Scheme 103: Peptide-catalyzed atroposelective ring-opening of lactones.
Scheme 104: Peptide-catalyzed coupling of 2-naphthols with quinones.
Scheme 105: Atroposelective nucleophilic aromatic substitution of fluoroarenes.
Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning
- Pablo Quijano Velasco,
- Kedar Hippalgaonkar and
- Balamurugan Ramalingam
Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3
- substantial resources and are labor-intensive, often exploring only a single variable in search of the optimal conditions while disregarding the intricate interactions among competing variables within the synthesis process. The complexity of the problem requires consideration that process optimization often
Graphical Abstract
Figure 1: A high-level representation of the workflow and framework used for the optimization of organic reac...
Figure 2: (a) Photograph showing a Chemspeed HTE platform using 96-well reaction blocks. (b) Mobile robot equ...
Figure 3: (a) Description of a slug flow platform developed using segments of gas as separation medium for hi...
Figure 4: Schematic representation (a) and photograph (b) of the flow parallel synthesizer intelligently desi...
Figure 5: (a) Schematic representation of an ASFR for obtaining an optimal solution with minimal human interv...
Figure 6: (a) A modular flow platform developed for a wider variety of chemical syntheses. (b) Various catego...
Figure 7: Implementation of four complementary PATs into the optimization process of a three-step synthesis.
Figure 8: Overlay of several Raman spectra of a single condition featuring the styrene vinyl region (a) and t...
Figure 9: (a) Schematic description of the process of chemical reaction optimization through ML methods. (b) ...
Figure 10: (a) Comparison between a standard GP (single-task) and a multitask GP. Training an auxiliary task u...
Figure 11: Comparison of the reaction yield between optimizations campaign where the catalyst ligand selection...
Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina
- Shin-ichiro Kurimoto,
- Kouta Inoue,
- Taito Ohno and
- Takaaki Kubota
Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267
- ]undeca-2,7,9-trien-4-ol moiety classified as psammaplysin derivatives. About 50 psammaplysin derivatives have been identified so far [2][3]. Among bromotyrosine alkaloids, the psammaplysin derivatives are particularly intriguing due to their structural complexity and biological activities. Psammaplysin
Graphical Abstract
Figure 1: Structures of ceratinadin G (1) and psammaplysin F (2).
Figure 2: Selected 2D NMR correlations for ceratinadin G (1).
Figure 3: ECD spectra of ceratinadin G (1) and psammaplysin F (2) in MeOH.
Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction
- Cesia M. Aguilar-Morales,
- América A. Frías-López,
- Nadia V. Emilio-Velázquez,
- Alejandro Islas-Jácome,
- Angelica Judith Granados-López,
- Jorge Gustavo Araujo-Huitrado,
- Yamilé López-Hernández,
- Hiram Hernández-López,
- Luis Chacón-García,
- Jesús Adrián López and
- Carlos J. Cortés-García
Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256
- structural diversity and complexity compared to classical 3- or 4-CRs [17][18][19]. In the same context, the hybridization of 1,5-disubstituted tetrazoles with an indole moiety using I-MCRs such as the Ugi-azide reaction as a key step, is very limited. To our knowledge, only three reactions have been
- -disubstituted tetrazole-methanesulfonylindole derivatives, with yields ranging from 16% to 55% after purification by column chromatography. Despite some yields being modest, they are deemed reasonable considering the reaction’s structural complexity, atom economy, and the efficiency achieved in terms of time
Graphical Abstract
Scheme 1: Synthetic approaches to obtain the 1,5-disubstituted tetrazole-indole system and our synthetic appr...
Scheme 2: High-order multicomponent reaction for the synthesis of 1,5-disubstituted tetrazol-methanesulfonyli...
Scheme 3: Plausible reaction mechanism for the synthesis of target molecules 18a–n.
Figure 1: Differential effect of the 1,5-disubstituted tetrazole-indole hybrid compounds 18a–j on proliferati...
Tailored charge-neutral self-assembled L2Zn2 container for taming oxalate
- David Ocklenburg and
- David Van Craen
Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250
- inevitable presence of counteranions necessary to balance the positive charge increases the complexity of the underlying equilibria. Competition between the desired guest and the counteranions can lead to significantly weakened binding strength of the target analyte in the worst case. One option to mitigate
Graphical Abstract
Figure 1: a) Generally desired guest recognition by encapsulation of the analyte within self-assembled metal-...
Scheme 1: Two-synthon approach for ligand preparation via CuAAC click reaction of an azide-functionalized, pr...
Figure 2: Recognition of mono- and dicarboxylates with [L2Zn2] which results in the formation of 1:1 host–gue...
Figure 3: a) Optimized structure (ωB97X‒D4 [83]/def2-SVP [84,85], implicit solvation with DMSO [86], ORCA 5.0.3 [81,82]) of [(C2)@L2...
Figure 4: 1H NMR competition experiments (500 MHz, 500 µM, DMSO-d6, 25 °C) with mixtures of studied analytes ...
Advances in radical peroxidation with hydroperoxides
- Oleg V. Bityukov,
- Pavel Yu. Serdyuchenko,
- Andrey S. Kirillov,
- Gennady I. Nikishin,
- Vera A. Vil’ and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249
- Kharasch–Sosnovsky peroxidation became the basic universal platform for the development of peroxidation methods, with its great potential for rapid generation of complexity due to the ability to couple the resulting free radicals with a wide range of partners. This review discusses the recent advances in
Graphical Abstract
Scheme 1: Organic peroxide initiators in polymer chemistry.
Scheme 2: Synthesis of organic peroxides.
Scheme 3: Richness of radical cascades with species formed from hydroperoxides in redox conditions.
Scheme 4: Co-catalyzed allylic peroxidation of alkenes 1 and 3 by TBHP.
Scheme 5: Allylic peroxidation of alkenes 6 by Pd(II)TBHP.
Scheme 6: Cu(I)-catalyzed allylic peroxidation.
Scheme 7: Enantioselective peroxidation of alkenes 10 with TBHP in the presence of copper(I) compounds.
Scheme 8: Oxidation of α-pinene (12) by the Cu(I)/TBHP system.
Scheme 9: Introduction of the tert-butylperoxy fragment into the α-position of cyclic ketones 15 and 17.
Scheme 10: α-Peroxidation of β-dicarbonyl compounds 19 using the Cu(II)/TBHP system.
Scheme 11: Co-catalyzed peroxidation of cyclic compounds 21 with TBHP.
Scheme 12: Co-, Mn- and Fe-catalyzed peroxidation of 2-oxoindoles 23, barbituric acids 25, and 4-hydroxycoumar...
Scheme 13: Cu-catalyzed and metal-free peroxidation of barbituric acid derivatives 31 and 3,4-dihydro-1,4-benz...
Scheme 14: Electrochemical peroxidation of 1,3-dicarbonyl compounds 35.
Scheme 15: Peroxidation of β-dicarbonyl compounds, cyanoacetic esters and malonic esters 37 by the TBAI/TBHP s...
Scheme 16: Cu-catalyzed peroxidation of malonodinitriles and cyanoacetic esters 39 with TBHP.
Scheme 17: Mn-catalyzed remote peroxidation via trifluromethylation of double bond.
Scheme 18: Cu-catalyzed remote peroxidation via trifluromethylthiolation of double bond.
Scheme 19: Fe-, Mn-, and Ru-catalyzed peroxidation of alkylaromatics 45, 47, 49, and 51 with TBHP.
Scheme 20: Cu-catalyzed peroxidation of diphenylacetonitrile (53) with TBHP.
Scheme 21: Cu-catalyzed peroxidation of benzyl cyanides 60 with TBHP.
Scheme 22: Synthesis of tert-butylperoxy esters 63 from benzyl alcohols 62 using the TBAI/TBHP system.
Scheme 23: Enantioselective peroxidation of 2-phenylbutane (64) with TBHP and chiral Cu(I) complex.
Scheme 24: Photochemical synthesis of peroxides 67 from carboxylic acids 66.
Scheme 25: Photochemical peroxidation of benzylic C(sp3)–H.
Scheme 26: Cu- and Ru-catalyzed peroxidation of alkylamines with TBHP.
Scheme 27: Peroxidation of amides 76 with the TBAI/TBHP system.
Scheme 28: Fe-catalyzed functionalization of ethers 78 with TBHP.
Scheme 29: Synthesis of 4-(tert-butylperoxy)-5-phenyloxazol-2(3H)-ones 82 from benzyl alcohols 80 and isocyana...
Scheme 30: Fe- and Co-catalyzed peroxidation of alkanes with TBHP.
Scheme 31: Rh-catalyzed tert-butylperoxy dienone synthesis with TBHP.
Scheme 32: Rh- and Cu-catalyzed phenolic oxidation with TBHP.
Scheme 33: Metal-free peroxidation of phenols 94.
Scheme 34: Cu-catalyzed alkylation–peroxidation of acrylonitrile.
Scheme 35: Cu-catalyzed cycloalkylation–peroxidation of coumarins 99.
Scheme 36: Metal-free cycloalkylation–peroxidation of coumarins 102.
Scheme 37: Difunctionalization of indene 104 with tert-butylperoxy and alkyl groups.
Scheme 38: Acid-catalyzed radical addition of ketones (108, 111) and TBHP to alkenes 107 and acrylates 110.
Scheme 39: Cu-catalyzed alkylation–peroxidation of alkenes 113 with TBHP and diazo compounds 114.
Scheme 40: Cobalt(II)-catalyzed addition of TBHP and 1,3-dicarbonyl compound 116 to alkenes 117.
Scheme 41: Cu(0)- or Co(II)-catalyzed addition of TBHP and alcohols 120 to alkenes 119.
Scheme 42: Fe-catalyzed functionalization of allenes 122 with TBHP.
Scheme 43: Fe-catalyzed alkylation–peroxidation of alkenes 125 and 127.
Scheme 44: Fe- and Co-catalyzed alkylation–peroxidation of alkenes 130, 133 and 134 with TBHP and aldehydes as...
Scheme 45: Carbonylation–peroxidation of alkenes 137, 140, 143 with hydroperoxides and aldehydes.
Scheme 46: Carbamoylation–peroxidation of alkenes 146 with formamides and TBHP.
Scheme 47: TBAB-catalyzed carbonylation–peroxidation of alkenes.
Scheme 48: VOCl2-catalyzed carbonylation–peroxidation of alkenes 152.
Scheme 49: Acylation–peroxidation of alkenes 155 with aldehydes 156 and TBHP using photocatalysis.
Scheme 50: Cu-catalyzed peroxidation of styrenes 158.
Scheme 51: Fe-catalyzed acylation-peroxidation of alkenes 161 with carbazates 160 and TBHP.
Scheme 52: Difunctionalization of alkenes 163, 166 with TBHP and (per)fluoroalkyl halides.
Scheme 53: Difunctionalization of alkenes 169 and 172 with hydroperoxides and sodium (per)fluoromethyl sulfina...
Scheme 54: Trifluoromethylation–peroxidation of styrenes 175 using MOF Cu3(BTC)2 as a catalyst.
Scheme 55: Difunctionalization of alkenes 178 with tert-butylperoxy and dihalomethyl fragments.
Scheme 56: Difunctionalization of alkenes 180 with the tert-butylperoxy and dihalomethyl moieties.
Scheme 57: The nitration–peroxidation of alkenes 182 with t-BuONO and TBHP.
Scheme 58: Azidation–peroxidation of alkenes 184 with TMSN3 and TBHP.
Scheme 59: Co-catalyzed bisperoxidation of butadiene 186.
Scheme 60: Bisperoxidation of styrene (189) and acrylonitrile (192) with TBHP by Minisci.
Scheme 61: Mn-catalyzed synthesis of bis(tert-butyl)peroxides 195 from styrenes 194.
Scheme 62: Bisperoxidation of arylidene-9H-fluorenes 196 and 3-arylidene-2-oxoindoles 198 with TBHP under Mn-c...
Scheme 63: Synthesis of bisperoxides from styrenes 200 and 203 using the Ru and Rh catalysis.
Scheme 64: Iodine-catalyzed bisperoxidation of styrenes 206.
Scheme 65: Synthesis of di-tert-butylperoxyoxoindoles 210 from acrylic acid anilides 209 using a Pd(II)/TBHP o...
Scheme 66: Pinolation/peroxidation of styrenes 211 catalyzed by Cu(I).
Scheme 67: TBAI-catalyzed acyloxylation–peroxidation of alkenes 214 with carboxylic acids and TBHP.
Scheme 68: Difunctionalization of alkenes 217 with TBHP and water or alcohols.
Scheme 69: TBAI-catalyzed hydroxyperoxidation of 1,3-dienes 220.
Scheme 70: Hydroxyperoxidation of 1,3-dienes 220.
Scheme 71: Iodination/peroxidation of alkenes 223 with I2 and hydroperoxides.
Scheme 72: The reactions of cyclic enol ethers 226 and 228 with I2/ROOH system.
Scheme 73: Synthesis of 1-(tert-butylperoxy)-2-iodoethanes 231.
Scheme 74: Synthesis of 1-iodo-2-(tert-butylperoxy)ethanes 233.
Scheme 75: Cu-catalyzed phosphorylation–peroxidation of alkenes 234.
Scheme 76: Co-catalyzed phosphorylation–peroxidation of alkenes 237.
Scheme 77: Ag-catalyzed sulfonylation–peroxidation of alkenes 241.
Scheme 78: Co-catalyzed sulfonylation–peroxidation of alkenes 244.
Scheme 79: Synthesis of α/β-peroxysulfides 248 and 249 from styrenes 247.
Scheme 80: Cu-catalyzed trifluoromethylthiolation–peroxidation of alkenes 250 and allenes 252.
Scheme 81: Photocatalytic sulfonyl peroxidation of alkenes 254 via deamination of N-sulfonyl ketimines 255.
Scheme 82: Photoredox-catalyzed 1,4-peroxidation–sulfonylation of enynones 257.
Scheme 83: Cu-catalyzed silylperoxidation of α,β-unsaturated compounds 260 and enynes 261.
Scheme 84: Fe-catalyzed silyl peroxidation of alkenes.
Scheme 85: Cu-catalyzed germyl peroxidation of alkenes 267.
Scheme 86: TBAI-catalyzed intramolecular cyclization of diazo compounds 269 with further peroxidation.
Scheme 87: Co-catalyzed three-component coupling of benzamides 271, diazo compounds 272 and TBHP.
Scheme 88: Co-catalyzed esterification-peroxidation of diazo compounds 274 with TBHP and carboxylic acids 275.
Scheme 89: Cu-catalyzed alkylation–peroxidation of α-carbonylimines 277 or ketones 280.
Scheme 90: Mn-catalyzed ring-opening peroxidation of cyclobutanols 282 with TBHP.
Scheme 91: Peroxycyclization of tryptamines 284 with TBHP.
Scheme 92: Radical cyclization–peroxidation of homotryptamines 287.
Scheme 93: Iodine-catalyzed oxidative coupling of indoles 288, cyanoacetic esters and TBHP.
Scheme 94: Summary of metal-catalyzed peroxidation processes.
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
- advances have been made, there remain critical challenges and unmet needs that call for innovative approaches. One of the key motivations for this exploration is the increasing complexity and diversity of analytes that require detection in real-world scenarios. Traditional methods, while effective, often
- emission spectrum, unlike that observed with the europium(III) analogue. This result suggests potential variations in the luminescence response among terbium(III) analogues and highlights the complexity of the interaction between lanthanide complexes and gaseous H2S, and understanding the nuances of this
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].
Copper-catalyzed yne-allylic substitutions: concept and recent developments
- Shuang Yang and
- Xinqiang Fang
Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232
- catalytic strategy provided direct access to a range of chiral spiropyrazolones in good to high yields, displaying moderate to excellent enantiomeric excess (Scheme 47, 47a–l). The method represents a novel approach for the synthesis of enantioenriched spirocyclic compounds with structural complexity
Graphical Abstract
Scheme 1: Copper-catalyzed allylic and yne-allylic substitution.
Scheme 2: Challenges in achieving highly selective yne-allylic substitution.
Scheme 3: Yne-allylic substitutions using indoles and pyroles.
Scheme 4: Yne-allylic substitutions using amines.
Scheme 5: Yne-allylic substitution using 1,3-dicarbonyls.
Scheme 6: Postulated mechanism via copper acetylide-bonded allylic cation.
Scheme 7: Amine-participated asymmetric yne-allylic substitution.
Scheme 8: Asymmetric decarboxylative yne-allylic substitution.
Scheme 9: Asymmetric yne-allylic alkoxylation and alkylation.
Scheme 10: Proposed mechanism for Cu(I) system.
Scheme 11: Asymmetric yne-allylic dialkylamination.
Scheme 12: Proposed mechanism of yne-allylic dialkylamination.
Scheme 13: Asymmetric yne-allylic sulfonylation.
Scheme 14: Proposed mechanism of yne-allylic sulfonylation.
Scheme 15: Aymmetric yne-allylic substitutions using indoles and indolizines.
Scheme 16: Double yne-allylic substitutions using pyrrole.
Scheme 17: Proposed mechanism of yne-allylic substitution using electron-rich arenes.
Scheme 18: Aymmetric yne-allylic monofluoroalkylations.
Scheme 19: Proposed mechanism.
Scheme 20: Aymmetric yne-allylic substitution of yne-allylic esters with anthrones.
Scheme 21: Aymmetric yne-allylic substitution of yne-allylic esters with coumarins.
Scheme 22: Aymmetric yne-allylic substitution of with coumarins by Lin.
Scheme 23: Proposed mechanism.
Scheme 24: Amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 25: Arylation by alkynylcopper driven dearomatization and rearomatization.
Scheme 26: Remote substitution/cyclization/1,5-H shift process.
Scheme 27: Proposed mechanism.
Scheme 28: Arylation or amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 29: Remote nucleophilic substitution of 5-ethynylthiophene esters.
Scheme 30: Proposed mechanism.
Scheme 31: [4 + 1] annulation of yne-allylic esters and cyclic 1,3-dicarbonyls.
Scheme 32: Asymmetric [4 + 1] annulation of yne-allylic esters.
Scheme 33: Proposed mechanism.
Scheme 34: Asymmetric [3 + 2] annulation of yne-allylic esters.
Scheme 35: Postulated annulation step.
Scheme 36: [4 + 1] Annulations of vinyl ethynylethylene carbonates and 1,3-dicarbonyls.
Scheme 37: Proposed mechanism.
Scheme 38: Formal [4 + 1] annulations with amines.
Scheme 39: Formal [4 + 2] annulations with hydrazines.
Scheme 40: Proposed mechanism.
Scheme 41: Dearomative annulation of 1-naphthols and yne-allylic esters.
Scheme 42: Dearomative annulation of phenols or 2-naphthols and yne-allylic esters.
Scheme 43: Postulated annulation mechanism.
Scheme 44: Dearomative annulation of phenols or 2-naphthols.
Scheme 45: Dearomative annulation of indoles.
Scheme 46: Postulated annulation step.
Scheme 47: Asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones.
Scheme 48: Proposed mechanism.
Scheme 49: Construction of C–C axially chiral arylpyrroles.
Scheme 50: Construction of C–N axially chiral arylpyrroles.
Scheme 51: Construction of chiral arylpyrroles with 1,2-di-axial chirality.
Scheme 52: Proposed mechanism.
Scheme 53: CO2 shuttling in yne-allylic substitution.
Scheme 54: CO2 fixing in yne-allylic substitution.
Scheme 55: Proposed mechanism.
Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light
- Francesco Gambuti,
- Jacopo Pizzorno,
- Chiara Lambruschini,
- Renata Riva and
- Lisa Moni
Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230
- ]. Among the common compound collections for drug discovery, the introduction of spirocyclic elements presents an attractive strategy for increasing molecular complexity without increasing molecular weight, and at the same time, for introducing structural novelty for patentability [3]. However, the
Graphical Abstract
Figure 1: Selected natural products containing spiro-indolenines.
Scheme 1: Synthesis of spiro[indole-heterocycles].
Scheme 2: Synthetic strategy for the new synthesis of 2,3-diaminoindolenines [21] and spiro[indole-isoquinolines]....
Scheme 3: Scope of the synthesis of spiro[indole-THIQs]. aα-aminoamidine 2b has been isolated (54%) too; bα-a...
Scheme 4: Two-step synthesis using p-methylaniline.
Scheme 5: Investigation of the one-pot four-step synthetic protocol employing N-Ph-benzoxazepine 5.
Figure 2: Time profile of the reaction of N-Ph-THIQ, 3,5-dimethoxyaniline and t-BuNC conducted under optimize...
Scheme 6: Proposed mechanism.
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
- based on an N/B pair, while the remaining six are P/B FLPs. Given the relative complexity of the mechanism studied, it was necessary to employ a 3D volcano plot using the energy span (δE) and two energies of the system. Analysis of the correlations revealed that the most suitable combination of energies
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...
Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels
- Connor R. M. MacDonald and
- Emily R. Draper
Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220
- leave the solvent deuterated. This gives the advantage of contrast matching, where parts of the molecule can be hidden so temporal mapping can be achieved, but all add to the cost and complexity of the experiments. This is discussed in more detail further on. A number of models exist which describe the
- macroscopic irradiated volume [10]. This makes the meaningful application of SAS techniques to heterogeneous systems challenging [72]. As the topological complexity of the system increases, so too does the difficulty of modelling the data. This can result in the number of modelling parameters becoming
Graphical Abstract
Figure 1: Hierarchical assembly occurring across length scales. Molecular interactions result in fibres which...
Figure 2: Three-dimensional CLSM image of a multicomponent supramolecular structure. The three-dimensional CL...
Figure 3: AFM images of air-dried aqueous Fmoc-FF, Fmoc-S, and 1:1 Fmoc-FF:Fmoc-S solutions. Figure 3 was reprinted f...
Figure 4: (a) 3D CLSM images of macroscopically a self-sorting gel network, where all fibres were stained gre...
Figure 5: (a) 3D AFM topographic image of dried elastin fibre. (b) Indicative height and diameter profile plo...
Figure 6: The nano-to-micro imaging range of SEM and TEM [30]. Cartoons represent the nanoparticles, pores, nanow...
Figure 7: Cartoon of artifacts caused by blotting and thinning. a) Alignment of threadlike micelles (left) [32] a...
Figure 8: (a) Chemical structures of monomer compounds and a schematic of the resulting chiral helical struct...
Figure 9: Commonly observed entanglements of urea-based supramolecular helices. (a) Double helix, (b) quadrup...
Figure 10: (a) SEM image of a single three-stranded braid showing a defect in which the braid separates into s...
Figure 11: Visualization of individual atoms at 1.25 Å resolution. Three apoferritin residues are shown at hig...
Figure 12: Cartoon of a general small-angle scattering setup.
Figure 13: (a) SAXS data and fits for solution in H2O (open symbols) and D2O (closed symbols). Cryo-TEM data f...
Figure 14: (a) A cartoon illustrating the orientation phases caused by shear alignment of WLMs. (b) Rheologica...
Figure 15: (a) Chemical structure of 2NapFF and (b) a cartoon cross-section of the hollow cylinder structure f...
Figure 16: Length scales of scattering and imaging techniques [16,54,55].
Figure 17: A schematic of a hydrogel network showing the significance of various parameters extracted from SAN...
Figure 18: The morphologies of a co-assembled complex dependent on the solvent composition. Figure 18 is from [89] and was ...
Figure 19: Allowed and forbidden crossings of entangled helices. Figure 19 is from [44] and was adapted by permission from ...
Figure 20: (a) Cryo-TEM density map of self-assembled (ʟ,ʟ)-2NapFF. (b) Computational model fit to cryo-TEM ma...
Figure 21: Map showing an incomplete list of global scientific centres providing access to (a) cryo-EM in red ...
Figure 22: SANS at a range of times. Solid lines are fits to a hollow cylinder model (T = 114 min and T = 202 ...
Figure 23: SAXS data of 5 mg/mL alanine-functionalised perylene bisimide (PBI-A) in 20 v/v % MeOH at pH (a) 2;...
Figure 24: Cryo-TEM sample prepared using plunge freezing in liquid nitrogen slush and sublimed for 30 minutes...
Machine learning-guided strategies for reaction conditions design and optimization
- Lung-Yi Chen and
- Yi-Pei Li
Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212
- compute reaction enthalpy for particular types of reactions [30], this approach often demands significant computational resources to determine accurate TSs and activation energies. The complexity increases further when considering the impacts of solvents and catalysts, which means that large-scale
- procedure can provide valuable chemical insights into graph-based reaction encoding, as it reveals how the reaction center atoms influence the bond breaking and formation. However, obtaining accurate AAM for reactions can be difficult and depends on the complexity of the reaction types, as shown by Lin et
Graphical Abstract
Figure 1: Schematic diagram illustrating the data mining and preprocessing steps for chemical reaction datase...
Figure 2: A comparison of three types of reaction embedding methods: (A) descriptor-based, which use predefin...
Figure 3: A schematic diagram of how ML algorithms can be combined with HTE platforms to optimize reaction co...
Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles
- Yutaro Miyashita,
- Sae Someya,
- Tomoko Kawasaki-Takasuka,
- Tomohiro Agou and
- Takashi Yamazaki
Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206
- (17%) were employed instead of nitroacetate, while no other compound was separated from these mixtures due to their complexity (Scheme 6). Reactions of (E)-4,4,4-trifluoro-2,3-epoxybutanoate 2b with Grignard-based copper reagents Despite the previous report by the Seebach group on the intriguing
Graphical Abstract
Scheme 1: Expectation of the regio- as well as stereoselective reactions of 2.
Scheme 2: Attempts of the present epoxidation to other α,β-unsaturated esters, 1h–j.
Figure 1: Crystallographic structure of the epoxy ring-opening products by PhCH(NH2)Me (3bd) and PhCH2SH (4ba...
Scheme 3: Introduction of additional halogen atoms at the 2-position of the compound 2b.
Scheme 4: Clarification of the stereochemistry of anti,syn-8a and -7b.
Figure 2: Crystallographic structure of anti,syn-8a.
Scheme 5: Reaction of 2b with other stabilized nucleophiles.
Scheme 6: Production of 4,4,4-trifluoro-2,3-dihydroxybutanoate anti-10a.
Scheme 7: Reactions of n-C10H21MgBr-based cuprate with 13f as well as 2b with/without D2O quenching.
Figure 3: A part of 13C NMR spectra for the compounds 11a and 11a-D.
Asymmetric organocatalytic synthesis of chiral homoallylic amines
- Nikolay S. Kondratyev and
- Andrei V. Malkov
Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201
- -trifluoromethylamine derivatives of high molecular complexity (Scheme 28). The process involves a highly enantioselective reaction of the isatin-derived Morita–Baylis–Hillman carbonate 137 with a novel α-CF3-substituted imine 136, derived from inexpensive benzothiophene-2,3-dione. A C2-symmetrical cinchona-derived
Graphical Abstract
Scheme 1: The position of homoallylic amines in the landscape of alkaloid and nitrogen compounds syntheses.
Scheme 2: 3,3’-Diaryl-BINOL-catalysed asymmetric organocatalytic allylation of acylimines [24].
Scheme 3: Aminophenol-catalysed reaction between N-phosphinoylimines and pinacol allylboronic ester. Imine sc...
Scheme 4: Asymmetric geranylation and prenylation of indoles catalysed by (R)- or (S)-3,3’-dibromo-BINOL [25]. aA...
Scheme 5: (R)-3,3’-Di(3,5-di(trifluoromethyl)phenyl-BINOL-catalysed asymmetric geranylation and prenylation o...
Scheme 6: Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’...
Scheme 7: Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’...
Scheme 8: Kinetic resolution of chiral secondary allylboronates [15,30].
Scheme 9: (E)-Stereospecific asymmetric α-trifluoromethylallylation of cyclic imines and hydrazones [31].
Scheme 10: Hosomi–Sakurai-type allylation of in situ-formed N-Fmoc aldimines [32].
Figure 1: Two different pathways for the Hosomi–Sakurai reaction of allyltrimethylsilane with N-Fmoc aldimine...
Scheme 11: Chiral squaramide-catalysed hydrogen bond-assisted chloride abstraction–allylation of N-carbamoyl α...
Figure 2: The pyrrolidine unit gem-methyl group conformational control in the squaramide-based catalyst [34].
Figure 3: The energetic difference between the transition states of the two proposed modes of the reaction (SN...
Scheme 12: One-pot preparation procedure for oxazaborolidinium ion (COBI) 63 [37].
Scheme 13: Chiral oxazaborolidinium ion (COBI)-catalysed allylation of N-(2-hydroxy)phenylimines with allyltri...
Scheme 14: The two-step N-(2-hydroxy)phenyl group deprotection procedure [37].
Scheme 15: Low-temperature (−40 °C) NMR experiments evidencing the reversible formation of the active COBI–imi...
Figure 4: Two computed reaction pathways for the COBI-catalysed Strecker reaction (TS1 identical to allylatio...
Scheme 16: Highly chemoselective and stereospecific synthesis of γ- and γ,δ-substituted homoallylic amines by ...
Scheme 17: Catalytic cycle for the three-component allylation with HBD/πAr–Ar catalyst [39].
Scheme 18: Reactivity of model electrophiles [39].
Scheme 19: HBD/πAr–Ar catalyst rational design and optimisation [39].
Scheme 20: Scope of the three-component HBD/πAr–Ar-catalysed reaction [39].
Scheme 21: Limitations of the HBD/πAr–Ar-catalysed reaction [39].
Scheme 22: Asymmetric chloride-directed dearomative allylation of in situ-generated N-acylquinolinium ions, ca...
Scheme 23: Chiral phosphoric acid-catalysed aza-Cope rearrangement of in situ-formed N-α,α’-diphenyl-(α’’-ally...
Scheme 24: Tandem (R)-VANOL-triborate-catalysed asymmetric aza-Cope rearrangement of in situ-formed aldimines ...
Scheme 25: (S)-TRIP-catalysed enantioconvergent aza-Cope rearrangement of β-formyl amides, substrate scope [43]. a...
Scheme 26: (S)-TRIP-catalysed enantioconvergent aza-Cope rearrangement of β-formyl amides 16–19, amide and all...
Scheme 27: Synthetic applications of homoallylic N-benzophenone imine products 131 [43].
Scheme 28: Chiral organocatalysed addition of 2,2,2-trifluoroethyl ketimines to isatin-derived Morita–Baylis–H...
Scheme 29: Chiral chinchona-derived amine-catalysed reaction between isatin-based Morita–Baylis–Hilman carbona...
Scheme 30: (R)-VAPOL-catalysed hydrogen atom transfer deracemisation [45].
Scheme 31: Chiral PA-catalysed [1,3]-rearrangement of ene-aldimines [46].
Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers
- Andreas Wiest and
- Pavel Kielkowski
Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199
- modified peptides resulting from the proteolytic digest of a whole proteome. In other words, the complexity of the whole proteome digest is beyond the coverage and sensitivity of today’s mass spectrometers. On the other hand, the enrichment of the probe–peptide conjugates necessitates larger amounts of
- modified proteins. The linkers releasing the reporter ion may serve as an interesting tool during transition from enrichment-based methods to direct ‘linker-free’ identification MS methods of desired probe–peptide conjugates. Enrichment-based chemical proteomics The pursuit to decrease the complexity of
Graphical Abstract
Figure 1: Overall chemical proteomics strategy to identify protein targets of natural products (NPs) and simi...
Figure 2: A) Design of mostly used photo-crosslinking groups. B) Mass spectrometry properties of proteins PTM...
Figure 3: Direct and indirect approach to identify protein targets and representative chemical proteomics wor...
Figure 4: Products of the CuAAC side reactions.
Figure 5: Search possibilities on peptide-level characterization. A) Comparison of DDA and DIA techniques. B)...
Figure 6: In-gel analysis using a tag with fluorophore (A) or via shift-assay (B).
Figure 7: Reporter linkers. A) DMP-tag. B) AzidoTMT tag. C) SOX-tag. D) Imidazolium tag. *A star indicates th...
Figure 8: Biotin and desthiobition-based sample linkers and their associated diagnostic peaks. A) Structure o...
Figure 9: A) isoDTB linker and probe-specific diagnostic ions (B). *A star indicates the possible introductio...
Figure 10: TEV-cleavable linker structure with its characteristic diagnostic ions (A) and probe-specific diagn...
Figure 11: A) Structure of the full length DADPS linker and remaining part after cleavage. B) Diagnostic ions....
Figure 12: Diagnostic peaks included in the search identify higher numbers of modified PSMs and peptides using...
Figure 13: An alternative DADPS linker.
Figure 14: Chemical structure of the trifunctional trypsin cleavable AzKTB linker.
Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis
- Stefan P. Schmid,
- Leon Schlosser,
- Frank Glorius and
- Kjell Jorner
Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196
Graphical Abstract
Figure 1: Schematic depiction of available data sources for predictive modelling, each with its advantages an...
Figure 2: Schematic depiction of different kinds of molecular representations for fluoronitroethane. Among th...
Figure 3: Depiction of the energy diagram of a generic enantioselective reaction. In the centre, catalyst and...
Figure 4: Hammett parameters are derived from the equilibrium constant of substituted benzoic acids (example ...
Figure 5: Selected examples of popular descriptors applied to model organocatalytic reactions. Descriptors en...
Figure 6: Example bromocyclization reaction from Toste and co-workers using a DABCOnium catalyst system and C...
Figure 7: Example from Neel et al. using a chiral ion pair catalyst for the selective fluorination of allylic...
Figure 8: Data set created by Denmark and co-workers for the CPA-catalysed thiol addition to N-acylimines [67]. T...
Figure 9: Selected examples of ML developments that used the dataset from Denmark and co-workers [67]. (A) Varnek...
Figure 10: Study from Reid and Sigman developing statistical models for CPA-catalysed nucleophilic addition re...
Figure 11: Selected examples of studies where mechanistic transferability was exploited to model multiple reac...
Figure 12: Generality approach by Denmark and co-workers [132] for the iodination of arylpyridines. From the releva...
Figure 13: Betinol et al. [133] clustered the relevant chemical space and then evaluated the average ee for every c...
Figure 14: Corminboeuf and co-workers [134] chose a representative subset of the reaction space (indicated by dark ...
Figure 15: Example for data-driven modelling to improve substrate and catalyst design. (A) C–N coupling cataly...
Figure 16: Example for utilising a genetic algorithm for catalyst design. (A) Morita–Baylis–Hillman reaction s...
Figure 17: Organocatalysed synthesis of spirooxindole analogues by Kondo et al. [171] (A) Reaction scheme of dienon...
Figure 18: Schematic depiction of required developments in order to overcome current limitations of ML for org...
Natural resorcylic lactones derived from alternariol
- Joachim Podlech
Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187
Graphical Abstract
Figure 1: Examples of compounds covered in this review categorized in six sub-classes (see text).
Figure 2: Examples of compounds not covered in this review.
Figure 3: Wrongly assigned and thus obsolete structures (details will be discussed in the respective chapters...
Figure 4: Alternariol with the correct IUPAC numbering and an occasionally used numbering based on the biphen...
Figure 5: Alternariol O-methyl ethers.
Figure 6: Alternariol O-glycosides.
Figure 7: Alternariol O-acetates and O-sulfates.
Figure 8: 2-Hydroxy- and 4-hydroxy-substituted alternariol and its O-methyl ethers.
Figure 9: Chloro- and amino-substituted alternariol and its O-methyl ethers.
Figure 10: Presumed alternariol derivatives with non-canonical substitution pattern.
Figure 11: Alternariol derivatives with the 1-methyl group hydroxylated.
Figure 12: Verrulactones: pseudo-dimeric derivatives of altertenuol and related compounds.
Figure 13: Biaryls formed by reductive lactone opening and/or by decarboxylation.
Figure 14: Altenuene and its diastereomers.
Figure 15: 9-O-Demethylated altenuene diastereomers.
Figure 16: Acetylated and methylated altenuene diastereomers.
Figure 17: Altenuene diastereomers modified with lactic acid, pyruvic acid, or acetone.
Figure 18: Neoaltenuene and related compounds.
Figure 19: Dehydroaltenusin and its derivatives.
Scheme 1: Equilibrium of dehydroaltenusin in polar solvents [278].
Figure 20: Further quinoid derivatives.
Figure 21: Dehydroaltenuenes.
Figure 22: Complex aggregates containing dehydroaltenuene substructures and related compounds.
Figure 23: Dihydroaltenuenes.
Figure 24: Altenuic acids and related compounds.
Figure 25: Cyclopentane- and cyclopentene-fused derivatives.
Figure 26: Cyclopentenone-fused derivatives.
Figure 27: Spiro-fused derivatives and a related ring-opened derivative.
Figure 28: Lactones-fused and lactone-substituted derivatives.
Scheme 2: Biosynthesis of alternariol [324].
Scheme 3: Biosynthesis of alternariol and its immediate successors with the genes involved in the respective ...
Scheme 4: Presumed formation of altenuene and its diastereomers and of botrallin.
Scheme 5: Presumed formation of altenuic acids and related compounds.
Scheme 6: A selection of plausible biosynthetic paths to cyclopenta-fused metabolites. (No stereochemistry is...
Scheme 7: Biomimetic synthesis of alternariol (1) by Harris and Hay [66].
Scheme 8: Total synthesis of alternariol (1) by Subba Rao et al. using a Diels–Alder approach [34].
Scheme 9: Total synthesis of alternariol (1) using a Suzuki strategy by Koch and Podlech [62], improved by Kim et...
Scheme 10: Total synthesis of alternariol (1) using an intramolecular biaryl coupling by Abe et al. [63].
Scheme 11: Total synthesis of altenuene (54) and isoaltenuene (55) by Podlech et al. [249].
Scheme 12: Total synthesis of neoaltenuene (69) by Podlech et al. [35].
Scheme 13: Total synthesis of TMC-264 (79) by Tatsuta et al. [185].
Scheme 14: Total synthesis of cephalosol (99) by Koert et al. [304].
Finding the most potent compounds using active learning on molecular pairs
- Zachary Fralish and
- Daniel Reker
Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185
- complexity of learning and predicting potency improvements between molecular pairs compared to simply identifying analogs of the most promising compound identified so far. However, AD-CP quickly caught up and rapidly (after 35 active learning iterations) outcompeted the single-molecule active learning
Graphical Abstract
Figure 1: Comparison of active learning approaches. (A) Classic exploitative active learning uses individual ...
Figure 2: The ActiveDelta approach improves exploitative active learning performance. (A–C) The percentage of...
Figure 3: D-MPNN-based model navigation of chemical space. T-SNE of a representative dataset (CHEMBL232-1, Al...
Figure 4: Tree-based model navigation of chemical space. T-SNE of a representative dataset (CHEMBL232-1, Alph...
Computational toolbox for the analysis of protein–glycan interactions
- Ferran Nieto-Fabregat,
- Maria Pia Lenza,
- Angela Marseglia,
- Cristina Di Carluccio,
- Antonio Molinaro,
- Alba Silipo and
- Roberta Marchetti
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
- interaction with host proteins [5][6]. Notably, the complexity of the glycome far surpasses that of the genome, transcriptome, and proteome, not only due to the structural and conformational diversity of glycans, whose synthesis is not template driven, but also due to their dynamic nature [5][6]. Although
- , depending on the values adopted by the torsional angles around the glycosidic linkages [10]. The high variability of linkages type, branching, stoichiometry, anomeric configuration (alpha and beta), and conformation contributes to the intricate nature of glycans. The complexity of the glycome is even higher
- in bacteria, which are able to use most of the mammalian sugar units to construct their glycoconjugates but, in addition, can also use a wide variety of particular, and potentially endless, monosaccharides that are instead not present in eukaryotes (Figure 2). This huge diversity and complexity
Graphical Abstract
Figure 1: Carbohydrate conformational variability. a) Illustration of Φ, Ψ and ω dihedral angles for a repres...
Figure 2: Monosaccharides diversity in eukaryotes and bacteria. a) Eukaryotic monosaccharides. b) Examples of...
Figure 3: Different glycan representations. The 3’-sialyllactosamine is depicted according to the a) IUPAC no...
Figure 4: Visualisation programs. Different representation of a protein–ligand complex by using the most used...
Figure 5: A schematic representation of useful computational methods to study protein–glycan interactions. a)...
Cage-like microstructures via sequential Ugi reactions in aqueous emulsions
- Rita S. Alqubelat,
- Yaroslava A. Menzorova and
- Maxim A. Mironov
Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179
- obtaining cage-like structures are characterized by technical complexity, a multi-stage nature, and low yield of target structures. To develop a one-step method for the synthesis of cage-like structures, it is necessary to control the deposition process of colloidal particles on the surface of emulsion
Graphical Abstract
Scheme 1: Synthesis of cross-linked microgel labelled with aminofluorescein.
Figure 1: Single droplets of the Pickering emulsion attached to a glass surface.
Figure 2: Cage-like microstructure obtained via sequential Ugi reactions.
Figure 3: AFM images of A) single domains and B) cross-linked CMC/chitosan polymer particles.
Figure 4: Variations of microstructures obtained via sequential Ugi reactions. A) Cap-like structures at 5 mo...
Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications
- Matteo Gasparetto,
- Balázs Fődi and
- Gellért Sipos
Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168
- complexity of DELs, there is only limited opportunity to track the efficiency of individual reactions during library synthesis. Therefore, BBs need to pass validation before being used in library synthesis settings. For these bifunctional amino esters, we performed a three-step validation where they were
Graphical Abstract
Scheme 1: Known and improved synthetic strategies to access α-(hetero)aryl-amino acids.
Scheme 2: Reformatsky reagent production.
Scheme 3: Scope of ethyl heteroarylacetates. Isolated yields are given. *Dark reactions were carried out for ...
Scheme 4: Telescoped flow synthesis of heteroarylacetates.
Scheme 5: Potential routes for the preparation of oximes.
Scheme 6: Oxime group insertion step.
Scheme 7: Amino ester production: general scheme, scope and gram scale experiment. The numbers in brackets re...
Scheme 8: Reactions scheme and results for the on-DNA experiments. The reported values represent the normaliz...
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
- Cristina Martini,
- Muhammad Idham Darussalam Mardjan and
- Andrea Basso
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
- Owing to the flexibility for variation of the GBB reaction, it has been widely employed in combination with other reactions for the formation of novel scaffolds with high level of complexity. The general approach to generate complex architectures is the installation of functional groups on the GBB
- /domino reaction, one-pot stepwise synthesis and multicomponent reaction. In the one-pot cascade reaction, the complexity of heterocycles was achieved due to the presence of functional groups formed in the GBB reaction which allow further reactions to occur. In the case of one-pot stepwise synthesis, the
- (41–67%). Multicomponent polymerizations are simple and efficient methods to construct a library of polymers with great structural complexity and diversity, including fused-heterocyclic polymers[64]. Tang et al. [65] reported the transition-metal-free multicomponent polymerization of dialdehydes 96a–c
Graphical Abstract
Scheme 1: Mechanism of the GBB reaction.
Scheme 2: Comparison of the performance of Sc(OTf)3 with some RE(OTf)3 in a model GBB reaction. Conditions: a...
Scheme 3: Comparison of the performance of various Brønsted acid catalysts in the synthesis of GBB adduct 6. ...
Scheme 4: Synthesis of Brønsted acidic ionic liquid catalyst 7. Conditions: a) neat, 60 °C, 24 h; b) TfOH, DC...
Scheme 5: Aryliodonium derivatives as organic catalysts in the GBB reaction. In the box the proposed binding ...
Scheme 6: DNA-encoded GBB reaction in micelles made of amphiphilic polymer 13. Conditions: a) 13 (50 equiv), ...
Scheme 7: GBB reaction catalyzed by cyclodextrin derivative 14. Conditions: a) 14 (1 mol %), water, 100 °C, 4...
Scheme 8: Proposed mode of activation of CALB. a) activation of the substrates; b) activation of the imine; c...
Scheme 9: One-pot GBB reaction–Suzuki coupling with a bifunctional hybrid biocatalyst. Conditions: a) Pd(0)-C...
Scheme 10: GBB reaction employing 5-HMF (23) as carbonyl component. Conditions: a) TFA (20 mol %), EtOH, 60 °C...
Scheme 11: GBB reaction with β-C-glucopyranosyl aldehyde 26. Conditions: a) InCl3 (20 mol %), MeOH, 70 °C, 2–3...
Scheme 12: GBB reaction with diacetylated 5-formyldeoxyuridine 29, followed by deacetylation of GBB adduct 30....
Scheme 13: GBB reaction with glycal aldehydes 32. Conditions: a) HFIP, 25 °C, 2–4 h.
Scheme 14: Vilsmeier–Haack formylation of 6-β-acetoxyvouacapane (34) and subsequent GBB reaction. Conditions: ...
Scheme 15: GBB reaction of 4-formlyl-PCP 37. Conditions: a) HOAc or HClO4, MeOH/DCM (2:3), rt, 3 d.
Scheme 16: GBB reaction with HexT-aldehyde 39. Conditions: a) 39 (20 nmol) and amidine (20 μmol), MeOH, rt, 6 ...
Scheme 17: GBB reaction of 2,4-diaminopirimidine 41. Conditions: a) Sc(OTf)3 (20 mol %), MeCN, 120 °C (MW), 1 ...
Scheme 18: Synthesis of N-edited guanine derivatives from 3,6-diamine-1,2,4-triazin-5-one 44. Conditions: a) S...
Scheme 19: Synthesis of 2-aminoimidazoles 49 by a Mannich-3CR followed by a one-pot intramolecular oxidative a...
Scheme 20: On DNA Suzuki–Miyaura reaction followed by GBB reaction. Conditions: a) CsOH, sSPhos-Pd-G2; b) AcOH...
Scheme 21: One-pot cascade synthesis of 5-iminoimidazoles. Conditions: a) Na2SO4, DMF, 220 °C (MW).
Scheme 22: GBB reaction of 5-amino-1H-imidazole-4-carbonile 57. Conditions: a) HClO4 (5 mol %), MeOH, rt, 24 h....
Scheme 23: One-pot cascade synthesis of indole-imidazo[1,2,a]pyridine hybrids. In blue the structural motif in...
Scheme 24: One-pot cascade synthesis of fused polycyclic indoles 67 or 69 from indole-3-carbaldehyde. Conditio...
Scheme 25: One-pot cascade synthesis of linked- and bridged polycyclic indoles from indole-2-carbaldehyde (70)...
Scheme 26: One-pot cascade synthesis of pentacyclic dihydroisoquinolines (X = N or CH). In blue the structural...
Scheme 27: One-pot stepwise synthesis of imidazopyridine-fused benzodiazepines 85. Conditions: a) p-TsOH (20 m...
Scheme 28: One-pot stepwise synthesis of benzoxazepinium-fused imidazothiazoles 89. Conditions: a) Yb(OTf)3 (2...
Scheme 29: One-pot stepwise synthesis of fused imidazo[4,5,b]pyridines 95. Conditions: a) HClO4, MeOH, rt, ove...
Scheme 30: Synthesis of heterocyclic polymers via the GBB reaction. Conditions: a) p-TsOH, EtOH, 70 °C, 24 h.
Scheme 31: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 32: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 33: GBB-like multicomponent reaction towards the synthesis of benzothiazolpyrroles (X = S) and benzoxaz...
Scheme 34: GBB-like multicomponent reaction towards the formation of imidazo[1,2,a]pyridines. Conditions: a) I2...
Scheme 35: Post-functionalization of GBB products via Ugi reaction. Conditions a) HClO4, DMF, rt, 24 h; b) MeO...
Scheme 36: Post-functionalization of GBB products via Click reaction. Conditions: a) solvent-free, 150 °C, 24 ...
Scheme 37: Post-functionalization of GBB products via cascade alkyne–allene isomerization–intramolecular nucle...
Scheme 38: Post-functionalization of GBB products via metal-catalyzed intramolecular N-arylation. In red and b...
Scheme 39: Post-functionalization of GBB products via isocyanide insertion (X = N or CH). Conditions: a) HClO4...
Scheme 40: Post-functionalization of GBB products via intramolecular nucleophilic addition to nitriles. Condit...
Scheme 41: Post-functionalization of GBB products via Pictet–Spengler cyclization. Conditions: a) 4 N HCl/diox...
Scheme 42: Post-functionalization of GBB products via O-alkylation. Conditions: a) TFA (20 mol %), EtOH, 120 °...
Scheme 43: Post-functionalization of GBB products via macrocyclization (X = -CH2CH2O-, -CH2-, -(CH2)4-). Condi...
Figure 1: Antibacterial activity of GBB-Ugi adducts 113 on both Gram-negative and Gram-positive strains.
Scheme 44: GBB multicomponent reaction using trimethoprim as the precursor. Conditions: a) Yb(OTf)3 or Y(OTf)3...
Figure 2: Antibacterial activity of GBB adducts 152 against MRSA and VRE; NA = not available.
Figure 3: Antibacterial activity of GBB adduct 153 against Leishmania amazonensis promastigotes and amastigot...
Figure 4: Antiviral and anticancer evaluation of the GBB adducts 154a and 154b. In vitro antiproliferative ac...
Figure 5: Anticancer activity of the GBB-furoxan hybrids 145b, 145c and 145d determined through antiprolifera...
Scheme 45: Synthesis and anticancer activity of the GBB-gossypol conjugates. Conditions: a) Sc(OTf)3 (10 mol %...
Figure 6: Anticancer activity of polyheterocycles 133a and 136a against human neuroblastoma. Clonogenic assay...
Figure 7: Development of GBB-adducts 158a and 158b as PD-L1 antagonists. HTRF assays were carried out against...
Figure 8: Development of imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines as TDP1 inhibitors. The SMM meth...
Figure 9: GBB adducts 164a–c as anticancer through in vitro HDACs inhibition assays. Additional cytotoxic ass...
Figure 10: GBB adducts 165, 166a and 166b as anti-inflammatory agents through HDAC6 inhibition; NA = not avail...
Scheme 46: GBB reaction of triphenylamine 167. Conditions: a) NH4Cl (10 mol %), MeOH, 80 °C (MW), 1 h.
Scheme 47: 1) Modified GBB-3CR. Conditions: a) TMSCN (1.0 equiv), Sc(OTf)3 (0.2 equiv), MeOH, 140 °C (MW), 20 ...
Scheme 48: GBB reaction to assemble imidazo-fused heterocycle dimers 172. Conditions: a) Sc(OTf)3 (20 mol %), ...
Figure 11: Model compounds 173 and 174, used to study the acid/base-triggered reversible fluorescence response...
Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships
- Sabyasachi Chakraborty,
- Eduardo Mayo Yanes and
- Renana Gershoni-Poranne
Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160
- a PAS’s rings and its various molecular properties remain elusive. Revealing these relationships can deepen our understanding of these systems, as well as pave the way toward efficient and effective design of new functional PASs. Given its breadth and complexity, a natural approach to exploring the
Graphical Abstract
Figure 1: A) The building blocks used in the COMPAS-2 datasets. B) Possible annulation types formed when comb...
Figure 2: Roadmap of the work described in this article. Three main criteria are defined in increasing struct...
Figure 3: Comparison between COMPAS-1 (blue) and COMPAS-2 (purple). A) Principal Moments of Inertia shape dis...
Figure 4: Distributions of electronic properties of the dataset. KDE plots of HOMO, LUMO, Gap, AIP, and AEA c...
Figure 5: KDE distributions of the HOMO, LUMO, and Gap separated and colored by the longest L for: A) all 9-r...
Figure 6: Distributions of molecular properties for 4n and (4n + 2) π-electron count systems, divided by the ...
Figure 7: Stacked histograms showing the prevalence of the different heteroatoms across different areas of th...
Figure 8: Distributions of electronic properties of the dataset. KDE plots of A) HOMO, B) LUMO, C) Gap, D) AI...
Figure 9: A) Scatter plot of the HOMO (x-axis) and LUMO (y-axis) values of the molecules in COMPAS-2. In each...
Figure 10: The effect of multiple heterocycles of a certain type on the A) HOMO, B) LUMO, and C) Gap. For all ...
