CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• porphyrin-carboline conjugate 85 [43] and porphyrin-psoralen conjugates 87 [44] as shown in Scheme 17. Firstly, zinc(II) porphyrin-carboline conjugate 84 and porphyrin-psoralen conjugate 86b were synthesized in good yields by the CuAAC reaction between porphyrin 81b and azide 82 or 83. Interestingly, the

• MeI in DMF to afford the cationic products 85 and 87 in good yields. The synthesized conjugates exhibited high photocytotoxicity towards A549 cancer cells as compared to a tumor-localizing and potent photosensitizing agent, TMPyP. Further, the authors discovered that the porphyrin-carboline conjugates

• . The CuAAC click reaction has been shown to bind a variety of chromophores bearing azide or alkyne groups to the porphyrin periphery, including coumarin, xanthone, DNA, ferrocene, corrole, fluorescein, carborane, BODIPY, graphene, carboline, fullerene, NDI, β-cyclodextrin, cholic acid, quinolone, etc

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• Nisha Devi Virender Singh Department of Chemistry, DAV University, Jalandhar-Pathankot National Highway (NH 44), Jalandhar, 144012, Punjab, India Department of Chemistry, Central University of Punjab, Bathinda, India 10.3762/bjoc.18.92 Abstract β-Carboline is a privileged class of the alkaloid

• family and is associated with a broad spectrum of biological properties. 3-Formyl-9H-pyrido[3,4-b]indole is a such potent precursor belonging to this family which can be tailored for installing diversity at various positions of β-carboline to generate unique molecular hybrids of biological importance

• . The present work is a step towards this and assimilates the results related to the exploration of 3-formyl-9H-β-carbolines for the synthesis of β-carboline C-3 substituted MBH adducts followed by evaluation of their fluorescent characteristic. The effect of contact time, solvent system, concentration

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• investigated the cyanation of differently substituted 7-azaindoles and achieved excellent results. They also succeeded in applying this strategy to N-aryl-α-carbolines to synthesize the respective cyanated N-aryl-α-carboline products. 3 Photocatalyzed cyanation reactions Nowadays photocatalysis has emerged as

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

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

• cancer cells. Keywords: γ-carboline; cascade reaction; cell uptake; cytotoxicity; fluorescence; Introduction Carbolines are privileged aza-heterocycles found in the core of several natural and synthetic compounds and are known for their biological applications. Among the four different isomers, 9H

• -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

• shown promising biological activities in preclinical and clinical studies (Figure 1) [2][3][4][5][6]. The pyrimidine-γ-carboline alkaloid ingenine B (isolated from an Indonesian sponge) exhibits a pronounced cytotoxicity against a murine lymphoma cell line [7] and several isocanthine analogs are

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

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

• structures of the compounds were elucidated through 1D and 2D NMR spectroscopy. It was determined that trigonoine A was a β-carboline alkaloid containing a 2,8-diazabicyclo[3.3.1]nonane ring system, while trigonoine B (1) was formed by a combination of 2,3-dihydroquinolin-4-one and 3H-pyrrolo[2,3-c]quinoline

• rearranged from a β-carboline skeleton (Figure 1). Additionally, the antihepatitis B virus (HBV) activity of the alkaloids was evaluated in vitro using an HBV-transfected HepG2 cell line. The antihuman immunodeficiency virus (HIV) properties were also investigated to determine whether trigonoine A and B

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• ]. Similarly, Maurya developed a microfluidic photoreactor for the synthesis of a fused β-carboline from an α-ketovinyl azide and a 1,2,3,4-tetrahydro-β-carboline (Scheme 1b) [30]. More recently, Kappe reported the generation of 2H-azirines under continuous flow conditions, and their transformation into

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• octahydroindole [10], tetrahydroquinoline [11], tetrahydroisoquinoline [11][12], β-carboline [13], morpholine [14], and isoindoline [15] moieties have been developed. Obtained in an enantiomerically pure form, phosphonoproline and its analogues [16][17][18][19] were among the first compounds in this series

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

• -metal-free strategy is presented to access novel β-carboline-tethered benzothiophenone derivatives from 1(3)-formyl-β-carbolines using elemental sulfur activated by Et3N/DMSO. This expeditious catalyst-free reaction proceeds through the formation of β-carboline-based 2-nitrochalcones followed by an

• incorporation of sulfur to generate multifunctional β-carboline-linked benzothiophenones in good to excellent yields. The synthetic strategy could also be extended towards the synthesis of β-carboline-linked benzothiophenes. Moreover, the afforded products emerged as promising fluorophores and displayed

• 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

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• , giving selectively the C-2-substituted product in moderate to excellent yield (Scheme 27a). However, only traces of the product were detected employing benzoxazole. Six-membered heteroaromatic compounds, such as pyridine, pyrazine, quinazoline, and even carboline, in some cases fused to a benzene ring

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• reaction for accessing bioactive organic molecules is found in the complex synthesis of manzamine alkaloids. These efficient antitumor agents, originally isolated from several genera of marine sponges, contain a pentacyclic core with a pendant β-carboline moiety. Their total synthesis implies an elaborate

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• were found to produce the same compound. So far, pigmentosin A (1) was reported only from lichenized fungi [20][21], and thus this is the first report of this compound stemming from another group of fungi. Recently, we have reported on the two new β-carboline alkaloid derivatives gibellamines A and B

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• requires the use of 4 mol % of Pd2(dba)3, 12 mol % of Xantphos, 2.8 equivalents of Cs2CO3 and 1.2 equivalents of benzylamine to afford the corresponding δ-carboline in a 65% yield. Two years later, the group of Nachtsheim has designed a similar strategy for the preparation of N-(aryl)carbazoles 61 from

• diaryl-λ3-iodanes. Sequential difunctionalization of cyclic diaryl-λ3-iodanes. Double Suzuki–Miyaura coupling reaction of cyclic diaryl-λ3-iodanes. Synthesis of a δ-carboline from cyclic diaryl-λ3-iodane. Synthesis of N-(aryl)carbazoles from cyclic diaryl-λ3-iodanes. Synthesis of carbazoles from cyclic

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• , the synthesis of 2,3,4,9-tetrahydro-1H-xantene-1-ones (20) has been published by the same research group. The synthetic protocol was then extended to isolate benzo[a]xanthen-11-ones or chromeno[3,2-g]β-carboline-8,13-dione starting from 2-naphthol and 1H-β-carboline-1-one Mannich bases [71]. Although

• of Evodia rutaecarpa alkaloids, starting from 6-methoxy-4,9-dihydro-β-carboline and various substituted 1-aminoalkyl-2-naphthols [84] (Scheme 5). Reactions with electron rich aromatic compounds The formation of aza-o-QMs is also possible, if the initial phenolic Mannich base bears an aromatic moiety

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• -carboline derivative 52 starting from 51 (Scheme 15). In this case potassium dichromate (K2Cr2O7) was used as an oxidant in glacial acetic acid. The reaction completes within 5 minutes with excellent yield of the final product. Not very many metal oxidants have been explored to transform aromatic Schiff's

• carbon in oxidative dehydrogenation was also well explored in the last few decades. In most of these reactions, either an additive or an acceptor is used along with palladium to improve the rate of the reaction. Recently Török et al. [95] reported the synthesis of 1-aryl-β-carboline using montmorillonite

• K-10 and Pd/C as catalysts. The microwave-assisted synthesis of β-carboline 96 from tetrahydro-β-carboline 95 using catalytic Pd/C and lithium carbonate at high temperature is also reported [96]. This high yielding procedure gets completed within a few minutes (Scheme 36). Although the reaction

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• , recently, we have reported the activation of an imide carbonyl group with TfOH, for the synthesis of tetrahydroisoquinoline (THIQ) and tetrahydro-β-carboline (THBC) skeletons and related alkaloids [22][23][24][25][26]. The present study, describes the synthesis of 4-benzenesulfonylpiperazine-2,6-dione

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• electron-rich diene, which reacts with substituted dihydroisoquinoline 14 and dihydro-β-carboline 15, so that cyclohexanone derivatives 16 and 17 will be produced, respectively (Scheme 8) [19]. Also, a cyclic derivative of 13 was utilized (not shown). This aza-Diels–Alder reaction provides products with

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• analogues received less attention with respect to others congeners. Constraints and modifications in the tryptophan core have been mainly attained following two different strategies: embodying the nitrogen atom of the amino acid function in a β-carboline framework or inserting a linking group between the α

• -1,2,3,4-tetrahydrocarbazole-3-carboxylic acid as a rigid analogue of α-methyltryptophan, a well known unnatural amino acid able to inhibit α-chymotrypsin activity, Figure 2 (A). Hardening tryptophan in β-carboline or carbazole frameworks has been used by Hénichart and co-workers in their studies devoted

• hormone (GnRH) [13][14], Figure 2 (C). Finally, in the field of therapeutic peptides, constrained tryptophan residues of the β-carboline family (L-Tpi and D-Tpi), were used by Grieco and co-workers in the study and development of urotensin-II receptor (UTR) peptide ligands [15], Figure 2 (D). Switching

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• ; Introduction The presence of a β-carbolinone skeleton in various natural products, such as secofascaplysin A (I), SL651498 (II) (Figure 1), and their remarkable biological and pharmacological properties make them stand out amongst all the carboline class of compounds [1][2][3][4][5][6][7][8][9][10][11][12

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ] and anticancer [5] activities. The bioactive β-carboline alkaloids canthinone [6] and vinpocitine [7] also bear these substructures. Vinpocetine is a dehydrated derivative of the natural alkaloid of vincamine [8]. It is reported to have cerebral blood-flow enhancing [7] and neuroprotective effects [9

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• – 500085, India 10.3762/bjoc.10.45 Abstract A novel synthetic methodology has been developed for the synthesis of dihydro-β-carboline derivatives employing oxidative amidation–Bischler–Napieralski reaction conditions using tryptamine and 2,2-dibromo-1-phenylethanone as key starting materials. A number of

• dihydro-β-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-β-carbolines to naturally occurring eudistomin alkaloids. Keywords: Bischler–Napieralski reaction; dihydro-β-carboline derivatives; dihydro

• -eudistomin; eudistomin; keto amide; oxidative amidation; Introduction β-Carboline alkaloids [1] are widespread in plants, animals and some are formed naturally in the biological system. Rinehart et al. [2] reported the isolation of β-carboline alkaloids such as eudistomins [3] and several of its analogues

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• has been performed using the sequence of the Ugi multicomponent reaction and Cu(I)-catalyzed click chemistry. The effect of obtained γ-carboline–peptide conjugates on the rat liver mitochondria was evaluated. It was found that all compounds in the concentration of 30 µM did onot induce depolarization

• view, mitochondria and the MPT process are very attractive targets for the search of new neuroprotective agents [4][5]. Several promising mitochondria-targeting neuroprotectors have been reported in the literature. Thus, the antihistaminic drug dimebon [6][7], which relates to tetrahydro-γ-carboline