Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• of Technology Indore, Khandwa Road, Simrol, Indore-453 552, India, School of Chemical Sciences, National Institute of Science Education and Research, Bhubaneswar-752 050, Odisha, India 10.3762/bjoc.17.101 Abstract 1,5-Disubstituted indole-2-carboxaldehyde derivatives 1a–h and glycine alkyl esters 2a

• -pyrido[3,4-b]indole (β-carboline) is the most naturally abundant, present for instance, in the alkaloid harmine, a well-known selective inhibitor of monoamine oxidase-A (MAO-A) [1]. On the contrary, 5H-pyrido[4,3-b]indoles (γ-carbolines) are comparatively less examined, although these heterocycles have

• decomposition of N-pyridylbenzotriazoles. Later, the reaction conditions were modified to make this reaction more versatile and operationally simple such as by the use of microwave irradiation [12]. Meanwhile, the Fischer indole synthesis was successfully extended for the synthesis of significant biologically

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• . The heterocyclic structures which were found to be attached to these double-headed nucleosides include triazolophthalazine [11], 4,6-di-tert-butylbenzoxazole [12], mesitylisoxazole [13], 5-trimethylsilyl-1,2,3-triazole [14], 1-pivaloyloxymethyl-1H-1,2,3-triazole [15], 1,3,4-oxadiazino[6,5-b]indole [16

• ], 6,7-dihydro-6-oxo-5H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazine [17], 1,2,4-triazino[5,6-b]indole [18], 1,3,4-thiadiazoline [19], 1,3,4-oxadiazoline [19], 1,2,4-triazoline [19], 3-mercapto-1H-1,2,4-triazole [20], 1,3,4-oxadiazole-2(3H)-thione [20], 4-amino-5-mercapto-4H-1,2,4-triazole [20], and 1,2,4

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• ) to the Chair of Chemistry, Turin finally reacquired the international visibility in chemistry it had enjoyed with Sobrero and Peyrone and that the fatal contest of 1854 had eclipsed for more than a quarter of a century. In 1883, Fileti reported the first synthesis of indole and scatole, soon dwarfed

• and plant tissues. Many ptomaines are polyamines (putrescine, cadaverine), but others are not (indole, scatole). The name ptomaine (Leichengift in German) has disappeared from the modern lingo of organic chemistry because of the heterogeneous nature of these compounds. The formation of ptomaines was

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

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

• marketed drugs structured around indole implying its pharmacological significance such as oxypertine (27), ateviridine (28) [47] and spirooxindole-based potent cytotoxic agents 29, 30 and 31 [48]. In 2017, Lin and co-workers [49] designed a TFA-catalyzed three-component reaction for the regioselective

• molecules of arylglyoxal 33 and amine 32 under microwave irradiation with p-TsOH as a catalyst for the generation of a library of pyrazolopyridines in good yields (Scheme 57). The methyl substitution at the C-4 position of the aniline (p-toluidine-32b) led to the formation of azepino[5,4,3-cd]indole

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• 22 can be afforded easily (Scheme 7). This procedure offers a novel cyclization method with bifunctionalization, causing a multicomponent reaction of vinylaniline, halide, and sulfonylate to give corresponding indole derivatives. Furthermore, a wide variety of applicable substrates and good

• functional-group tolerance are provided by this approach, yielding multiple indole analogues with biological activity. In 2017, Liang and Bi [56] reported a visible-light-induced three-component cyclization of ethyl acetoacetate (23), perfluoroalkyl iodides 24, and guanidine hydrochloride (25) via a halogen

• ] cyclization. In 2020, Taylor and colleagues [26] proposed a reaction for the preparation of spirocyclic indoline derivative 47 from indolylynone 46 and thiophenol under blue-light irradiation (Scheme 16). An abundant range of products was given to test various indole-tethered ynones and thiols, confirming

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ]. We have previously reported the total syntheses of indolo[3,2-c]quinoline (isocryptolepine) [19], azaanthracenones (kalasinamide, marcanine A, and geovanine) [20], imidazo[4',5':4,5]pyrido[2,3-b]indole (grossularine-1 and -2) [21][22], imidazo[4,5-b]pyridine (2-amino-1-methyl-6-phenylimidazo[4,5-b

• synthesis of 2-aminopyridine derivatives through an electrocyclization of conjugated carbodiimides derived from an aza-Wittig reaction of iminophosphoranes and isocyanates [27]. Hibino and co-workers also achieved the preparation of mutagenic amino-α-carbolines (2-amino-9H-pyrido[2,3-b]indole, AαC) and

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• preferred gas-phase reaction. The ecology of marine bacteria in their interaction with algae is particularly interesting in which the bacteria can promote the algal growth, but can also kill their host [10][11]. For both processes, the phytohormone indole-3-acetic acid is used as a messenger molecule [10

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• common nitrogen-containing compounds such as pyridine, pyrazine, 1H-pyrazole, 1H-indole, 1-methyl-1H-indole, piperidine, and piperazine were subjected to screening. Pyridine and piperidine slightly hamper the reaction of 1g (Table 2, entries 2 and 7, 80–82%). Other nitrogen-containing compounds have more

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• (indole-2H5)tryptophan were performed, but none of these experiments resulted in a detectable incorporation of labeling. Conclusively, a non-biological origin of this part of the molecule seems likely, which may also explain why the detection of 41 in Celeribacter was not always reproducible. Notably, 2

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• )indole (10c) with 3 afforded the corresponding acetals 11a–c with 3-phenylbenzoheterole structures in 92%, 80%, and 93% yields, respectively. Acetals 11a–c successfully underwent TfOH-catalyzed cycloaromatization in HFIP to afford oxa-, thia-, and aza[4]helicenes 9a–c in 96%, 88%, and 93% yields

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• gallium-catalyzed synthesis of unsymmetrical CF3-substituted 3,3’- and 3,6’-bis(indolyl)methanes from trifluoromethylated 3-indolylmethanols [71]. Alcohol 61 reacts with indole 62 to provide a product 63 or 64, depending on the temperature (Scheme 17). The authors suggested that an indolium ion 65 is

• proposed that upon heating, Ga(OTf)3 reacts with 63 to release an indolium ion 65 and forms an organogallium species 67 via intermediate 66, which, after protodemetallation, releases indole 62 and regenerates the catalyst. The retro-Friedel–Crafts reaction at 80 °C at the indole C3-position thus allows the

• generate CF3-substituted iminium ions able to promote Friedel–Crafts alkylations [110][111]. Ma et al. exploited this mode of activation in a Brønsted acid-catalyzed three-component asymmetric reaction [112]. Mixing hemiacetal 175, arylaniline 176, and indole derivatives 149 in the presence of a catalytic

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• additional 1D 19F T1, T2, and CPMG relaxation dispersion experiments and solvent-induced isotope shift effects. This study also highlighted the particular advantages of employing 19F NMR fluorine probes strategically labelled in the second ring of the Trp indole moiety to directly measure conformational

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• Iwasawa and co-workers in 2011 [18][66] (Scheme 10A). Treatment of Boc-protected aniline 139 and n-butyl vinyl ether (140) with a platinum(II) catalyst afforded tricyclic indole 141 in 83% yield. The authors suggested that this catalytic [3 + 2] cycloaddition reaction may involve an α,β-unsaturated

• -workers used a platinum-catalyzed intramolecular [3 + 2] cycloaddition of a propargylic ketal derivative to complete the total synthesis of Kopsia indole alkaloids [67] (Scheme 11). The platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 afforded indoline 143 in 58

• intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl vinyl ether (140) gives tricyclic indole 141 [18][66]. (B) The proposed mechanism. (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to give indoline 143 [67]. (B) The proposed catalytic

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• autofluorescence of the peptide or protein. Here, we demonstrate the use of UVRR spectroscopy with 244 nm laser excitation for the characterization of GCP as well as guanidiniocarbonyl indole (GCI), a next generation supramolecular ligand for the recognition of carboxylates. For demonstrating the feasibility of

• the results from density functional theory (DFT) calculations. Keywords: GCI; GCP; guanidiniocarbonyl indole; guanidiniocarbonyl pyrrole; UVRR; Raman spectroscopy; resonance Raman; Introduction Supramolecular ligands are capable to selectively bind to peptides and proteins via reversible non

• supramolecular ligands: guanidiniocarbonyl pyrrole (GCP) and guanidiniocarbonyl indole (GCI). The latter class of artificial carboxylate receptors is a potential next generation binder based on the GCI motif which maintains the good carboxylate binding properties of GCP. GCI comprises an indole ring instead of a

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• activity in organic reactions. Tricyclic indole alkaloids bearing 3,4-fused seven-membered rings have attracted much attention because of their interesting molecular architectures and important biological activities [32][33]. Here the three-component reaction of 4-aminoindole (1a), 4-methylbenzaldehyde (2a

• ) and diethyl acetylenedicarboxylate (3a) was performed to construct the seven-membered indole ring system with the aid of the LS-FAS-Cu catalyst, and the results are summarized in Table 1. At the beginning, the three-component reaction was conducted without the presence of any catalyst, but no products

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• ]. Benzimidazoles are an important class of organic materials, and many derivatives of these group are biologically active [6][7][8][9]. The benzimidazole moiety “ […] is isosteric with indole and purine nuclei, which are present in a number of fundamental cellular components and bioactive compounds. Indeed, a

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -Nitrophenyl)thieno[3,2-b]thiophene (18) was similarly prepared by Pd-catalyzed Stille-type reaction of monostannylated thienothiophene 14 and o-iodonitrobenzene (17) in 86% yield. Successive Cadogan cyclization of 18 with triethyl phosphite under reflux gave tetracyclic 9H-thieno[2’,3’:4,5]thieno[3,2-b]indole

• heterotetracenes TTA, 9, 13, 19, 22, and 33, and heterohexacene 22. Synthesis of fused S,N-heterotetracene SN4 9 starting from thieno[3,2-b]thiophene (1). Synthesis of parent H-SN4 13 via the azide route. Synthesis of tetracyclic H-SN4 13 via the Cadogan route. Synthesis of tetracyclic indole derivative 19 via the

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

• and glutamine as well as the indole NH of tryptophan and some of the arginine NHε. This spectrum is also known as an amide finger print spectrum of a protein because the chemical shifts of the amides are very sensitive to both the secondary and tertiary structure. The amide signals, particularly for

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , thus rendering this methodology well suitable for the synthesis of a variety of indole derivatives. Subsequently, the panel of oxidative Heck coupling reactions via a photoredox catalytic system combined with C–H activation using Rh [74] or Ru [75] was extended by Rueping’s group. In 2014, Rueping

• applied to various C–H functionalization reactions [92][93]. In 2017, Noël, Van der Eycken and co-workers hence astutely combined the dual catalysis strategy with flow microreactor technology to achieve C2-acylation of indole derivatives with aldehydes (Figure 30) [94]. Both electron-rich and electron

• Figure 31. As previously, distinct catalytic cycles involving photoredox catalysis and C–H activation act in a cooperative way to promote the formation of a new bond. The strategy is based on the presence of a pyrimidine DG at the N1-position of the indole in order to facilitate the C–H activation step

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• excellent light-emitting properties with quantum yields (ΦF) up to 47%. Keywords: benzothiophene; β-carboline; metal-free; photophysical properties; sulfur insertion; Introduction The pyrido[3,4-b]indole moiety, commonly referred as β-carboline, is the core unit of about one quarter of all natural

• round-bottomed flask; 2-nitroacetophenone (0.080 mL, 0.587 mmol) was added at room temperature and the reaction mixture was stirred for 15 min. Thereafter, methyl 1-formyl-9-methyl-9H-pyrido[3,4-b]indole-3-carboxylate (1b, 0.15 g, 0.560 mmol) was added portionwise and the reaction mixture was allowed to

• gel (CHCl3/MeOH 95:5, v/v) to afford the analytically pure product 2bA as orange solid in 74% yield (two step yield). One-pot experimental procedure for the synthesis of methyl 1-(benzo[b]thiophene-2-carbonyl)-9H-pyrido[3,4-b]indole-3-carboxylate (6C). To a stirred suspension of Cs2CO3 (0.182 g, 0.560

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8

• -tetrahydrocinnoline) derivatives in moderate to excellent yields. Keywords: cinnoline; 1,4-diketone; indole; indolone; N-heterocycle; Introduction Nitrogen-containing heterocycles are widespread in plenty of molecules of interest, either in materials science, optics, electronics, or biology [1][2][3][4]. They are

• also very useful building blocks to create more sophisticated organic molecules. Therefore, the search for efficient methods for the synthesis of nitrogen-containing heterocycles is crucial to both organic and medicinal chemists. Among these, indole, indolone (1,5,6,7-tetrahydroindol-4-one), and

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole

• dimerization of indole under acidic conditions (Scheme 7) [8]. Electrophilic attack of indole protonated at position 3 toward the position 3 of another indole molecule, followed by deprotonation affords dimer-like derivative 20. The fundamental difference of this transformation from that we observed in the

• -like products 8a,b. Dimerization of indole under acidic conditions. Reaction of o-(pivaloylaminomethyl)benzaldehyde (1e) to give dimer-like products 23a and 23b. Yields of rearranged aldehydes 2 and dimer-like products 3 and 8 in two different solvents. Relative Gibbs free energy values corresponding