Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• Ranadeep Talukdar Department of Chemistry, Indian Institute of Technology Kharagpur, West Midnapore, West Bengal – 721302, India 10.3762/bjoc.17.137 Abstract Two or more indole molecules tailored to a single non-metal central atom, through any of their C2–7 positions are not only structurally

• catalytic and uncatalytic synthetic strategies adopted for the synthesis of the non-ionic (non-metallic) versions of these important molecules till date. Keywords: bisindole; heteroatom; indole; selenide; sulfide; Introduction Indole can be considered as a “prodigy” in the family of nitrogen-based

• in the spotlight of anticancer research recently. In line with this high importance associated with the molecules of current topic, i.e., more than one indole molecule flanked by a central atom, conglomeration of the available synthetic methods will have a high scientific value. This review will give

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• electrophiles, while maintaining a high degree of N-1 regioselectivity. Keywords: indazole; N-alkylation; regioselective; sodium hydride; tetrahydrofuran; Introduction Indazole (benzo[c]pyrazole) is an aromatic bicyclic heterocycle and can be viewed as a (bio)isostere of indole [1]. While only a few naturally

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• full agonists (54 and 55, Scheme 20A) [139]. Ackermann and co-workers presented a manganese(I)-catalyzed C–H allylation, installing α,β-unsaturated esters in peptide analogues bearing indole motifs (Scheme 22B) [140]. Starting with tryptophan, the enantioselective allylation reaction afforded the

• C-2 position of indole derivatives bearing peptide units in the C-3 position (Scheme 35A). This process led to several activated products in good yields, including one whose basic structure is already known to present important biological activities (106) [187] (Scheme 35B). Still in this work

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

• molecules like non-ribosomal peptides (NRP), polyketides (PK), terpenes or indole alkaloids [10][11]. The vast majority of fungal BGCs is found in the genomes of members of the Basidiomycota and Ascomycota including the genus Penicillium in which the first BGC was identified in 1990 [12][13][14

• (19) is a tryptophan-derived indole alkaloid which was so far only shown to be produced by A. fumigatus while other fumigaclavines can for example also be found in Penicillium ssp. (fumigaclavine A (18) and B (17)) [66][158]. In all fungi, alkaloid biosynthetic pathways share a common basis, starting

• mellonella [66]. Fumitremorgins The class of fumitremorgins comprises several diketopiperazine alkaloids which are tremorgenic mycotoxins. However, there are several fumitremorgin-like indole alkaloids including tryprostatins, spiro- and cyclotryprostatins and verruculogen besides fumitremorgins themselves

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• -protected indoles led to reduced indole products (indolines 82f and 82g). The substitution of the acrylonitrile group for an acrylate unit completely inhibited the reaction, whereas the replacement with an unactivated trisubstituted olefin unit led to cyclized products in lower yields (Scheme 30, 82h–k

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• ). Trapping lithiated Asmic with 1-methyl-1H-indole-3-carbonitrile afforded indole 7l whereas trapping with ethyl N-phenylformimidate afforded the selectively N-1 protected imidazole 7m (Scheme 2) [21]. Collectively, the condensations of lithiated Asmic with nitriles or an imidate provides an efficient route

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• , and scalability to obtain gram amounts for biological studies. Selected compounds were found to display affinity for cannabinoid receptors, which are promising drug targets for the treatment of inflammatory and neurodegenerative diseases. Keywords: alkylation of indole; anti-inflammatory; binding

• affinity; cannabinoid receptors; diindolylmethane; unsymmetrical 3,3'-diindolylmethane; Introduction Diindolylmethanes (DIMs) represent an important class of indole alkaloids, that are constituents of pharmaceuticals [1][2][3][4][5][6][7] and agrochemicals [8][9]. DIM derivatives possess a variety of

• via an iodine-catalyzed coupling reaction of trifluoromethyl(indolyl)phenylmethanol with indole derivatives. This method has also been extended to the synthesis of pentafluoro-ethylated and heptafluoro-propylated DIMs in excellent yields. Selected compounds were evaluated in radioligand binding

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