Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• already in clinical use as antiviral or anticancer drugs [2][5][6]. Bisphosphonates (BPs), the stable analogues of the natural pyrophosphate (Figure 1) found in cells, have been used for decades in the treatment of bone-related diseases, such as osteoporosis [7][8]. BPs can be categorized by the chemical

• analogues ApppI and ApppD (Z = Na or H). Synthetic route to target compound ApppI(d2) (Z = TBA). Supporting Information Supporting Information File 354: 1H, 13C, and 31P NMR spectra as well as HPCCC chromatogram of ApppI(d2) purification. Acknowledgements I would like to thank Mrs. Maritta Salminkoski for

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• devices and functional materials, the synthesis of corrole-based analogues has been rather limited due to very few synthetic methods developed to produce corroles with polymerizable substituents at the meso- or beta positions [10][11][12][13]. To date, meso-substituted corroles have been synthesized by

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• corresponding chemical libraries. Concerning hit to lead programs on a given target, if no new hits are available, previously reported leads along with new structural data can be pertinent starting points to design, prepare and assay original analogues. In conclusion, this text is an actual plea illustrating

• benzotriazol-containing hits which were the crucial starting points to independently reach promising corona viruses main protease inhibitors such as compounds 6 and 7. And this was only achieved following many iterations of structure-based design, synthesis and assays of analogues [78][81][82]. Also of concern

• analogues present in this library. If a screening of the full set will ensure their discovery, shrinking the library to a more manageable 150.000 compounds leads to a 0.29% odd of finding these three distinct singletons. On the other hand, had the original library contained several active compounds

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• ), Universidad de Valencia, C/Catedrático J. Beltrán 2, 46980 Paterna (Valencia), Spain School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, UK 10.3762/bjoc.18.136 Abstract We designed and synthesized two new ionic thermally activated delayed fluorescent (TADF) emitters that are charged analogues of

• introduced by Hatakeyama and co-workers, are typically p- and n-doped nanographenes [25][26]. OLEDs using MR-TADF emitters can simultaneously achieve narrowband emission and very high EQEmax. Inspired by our recent work on neutral MR-TADF emitters for OLEDs [27][28], we designed two charged analogues of

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• o-chloroarylketones are the starting material [27][28]. The preference for the use of o-bromo analogues is due to to the better yield obtained compared to using o-chloroarylhydrazones. However, the availability of commercial o-chloroarylaldehydes and o-chloroaryl ketones is greater than that of

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• , this has never been the subject of a report. Our recent interest in the preparation of 3,5-substituted-2-hydroxypyrazines (3, R2 = Ar and R3 = CH2Ar) as intermediates for the synthesis of marine luciferins analogues [29][30] along with the simplicity of this access drove us to study some of its aspects

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• China 10.3762/bjoc.18.90 Abstract γ-Phostams include γ-phosphonolactams and γ-phosphinolactams and their fused derivatives, phosphorus analogues of γ-lactams. They are 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides and important biological five-membered azaphosphaheterocycles. They have

• analogues of the corresponding lactams [11][12][13][14]. 1,2-Azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides, also called γ-phosphonolactams and γ-phosphinolactams, and their fused derivatives are important five-membered 1,2-azaphosphaheterocyclic derivatives. They are γ-phostams, phosphorus

• analogues of γ-lactams, showing various biological activities, such as anti-inflammatory [15][16], antioxidant [17][18], and antitumor [18][19][20] (Figure 1). Various synthetic methods of 1,2-azaphospholidine 2-oxide and 1,2-azaphospholine 2-oxide derivatives have been developed to date. Two major

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , trifluoromethyl radicals and its longer-chain analogues, share a common electrophilic character and a stabilizing stereoelectronic effect [14], we envisioned that the “dummy group” methodology could be translated into the formation of sought after perfluoroalkyl radicals (Scheme 1). In this work, we report the

• as N-phenylpyrrole and 2-phenylindole were found to produce large quantities of the desired perfluorohexyl and perfluorooctyl analogues as observed by both 1H NMR and GC–MS analysis. However, these molecules generated large concentrations of fluorinated byproducts which rendered separation of the

• perfluoroalkylsulfinates 2 and halogenated electrophilic partners. Left: isolated yields of synthesized perfluoroalkylating reagents: perfluorobutyl (1a), perfluorohexyl (1b), and perfluorooctyl (1c) analogues (after conversion of byproduct); middle: gram amounts of perfluorooctyl product 1c; right: UV–vis absorption of

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• excellently for most of the electron-rich anilines due to their increased nucleophilicity. A comparison of ortho-, meta- and para-substituted derivatives revealed that for electron-rich anilines, the para-substituted ABs are formed in better yields as their ortho- and meta-analogues. For example, the

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• ] exhibited excellent activity. No targeted synthesis of 8 exists; it was isolated in low yield as a side-product in the synthesis of KAR1 (1) [21]. In this reaction sequence, thiopyranthione 6b is the side-product in the pyranthione 6a synthesis and both analogues were progressed to the final furan ring

• values of 30 nM for MAO-B and 80 nM for AChE, respectively [20], and therefore, it represents a promising therapeutic potential against Alzheimer’s and Parkinson’s diseases. The goal of this work is the development of a targeted synthesis of 8 and other sulfur analogues of karrikins in order to study the

• effect of bioisosteric exchange together with the effect of substitution along the karrikin backbone on the inhibitory activity against AChE. The target sulfur analogues of karrikins are shown on Figure 2. Results and Discussion Synthesis of KAR analogues with sulfur in position C2 A series of thiones

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective. Keywords: chiral macrocycles; cooperative asymmetric catalysis; decarboxylative

• contrast, reactions catalyzed by acyclic analogues containing very similar structural units were non-selective, suggesting the essential role of the rigid macrocyclic framework in realizing efficient stereocontrol. With the easy synthesis, rich structural diversity, cooperative binding and activation sites

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• dithionite, Suhara and co-workers reported in their various works on the synthesis of vitamin K analogues, the use of menadione (10) to obtain 14 [113][114][115][116][117]. In these works, menadione (10) was reduced by using an aqueous 10% sodium dithionite solution in diethyl ether to furnish alcohol 14 in

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazine fragment on antifungal activity of the synthesized compounds, we have tested the activity of their analogues, unannulated 1,2,4,5-tetrazines 2c,g, containing the amidine moiety, and isomeric [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazines. For a comparative

• analysis of antifungal activity, the previously described [37] 3-methyl- and 3-phenyltriazolo[4,3-b][1,2,4,5]tetrazines 10a,b were used as structural analogues of compounds 3a,b. Furthermore, in the reactions of compound 10a with methanol, heptylamine and morpholine, new derivatives 11a–c have been

• -pyrazol-1-yl)-3-methyl-[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine (10a) with nucleophiles. In vitro fungistatic activity of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines 3a–k, 4a–c, 5a–c and their analogues. Supporting Information Supporting Information File 28: Experimental part. Acknowledgements Analytical

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• neuraminidase in relation to the analogues bearing hydrophobic substituents and ca. 5% for more polar substituents. These results suggest that polarity changes are less tolerated by neuraminidase due to the big difference in impact of hydrophobicity upon inhibition, thus indicating a simple approach to

• developed to date. The most potent TcTS inhibitors described are non-carbohydrate-based molecules (anthraquinones [14], chalcones and quinolones [15]) with low micromolar activity, whereas sialic acid-based analogues typically show high millimolar inhibitory activity [16], with few exceptions such as a

• sterically hindered active site (comparison shown with black arrows – Figure 5C and Figure 5D), which in turn conferred selectivity towards the neuraminidase. From the analogues perspective, the absence of TcTS inhibition could be also attributed to the lack of flexibility of the substituents rather than

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• calix[6]arene scaffold, we carried out the synthesis of three monomeric gold catalyst analogues A’,B’,C’(AuCl). The synthesis of these compounds was performed using the previously optimized protocol, starting from a 4-(octyloxy)aniline intermediate (Scheme 2). Subsequently, due to the general interest

• .), CH2Cl2, 0 °C to rt [A, 60%; B, 55%, C, 53%); iii) (Me2S)AuCl in CH2Cl2, 0 °C to rt (A(AuCl)2, 93%; B(AuCl)2, 74%; C(AuCl)2, 69%). Synthesis of the monomeric gold catalyst analogues A’,B’,C’(AuCl). Conditions: i) diphenylphosphinobenzoic acid, EDC∙HCl, DMAP (cat.), CH2Cl2, 0 °C to rt (A’, 71%; B’, 76%; C

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• using CPD as a precursor for high value-added fine chemicals such as a homocitric acid lactone was published by our group [19]. Since then we have developed synthetic pathways for lycoperdic acid [20] and nucleoside analogues [21] starting from CPD. The organocatalytic methods for the synthesis of

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1

• scaffolds with versatile medicinal properties, including anti-Alzheimer, anti-inflammatory, anticancer, antidiabetic, and antileishmanial activity [1]. Since the first synthesis of paullones (scaffold A in Figure 1) in 1992 [2], and disclosure of their Cdk inhibiting potential, several other analogues were

• ) was confirmed by the successful preparation of two closely related analogues, namely 3b, bearing a bromo substituent at position 11 of the backbone C (Scheme 6), and 3c, with an 8-membered azocinone ring instead of the 7-membered one. The synthesis of 3b started with a Fischer indole synthesis from

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product. Keywords: bicyclic AZT analogues; bridged homoarabinofuranosylpyrimidine nucleosides; chemical pathway; Lipozyme® TL IM; regioselective enzymatic

• acetylation; Introduction In the last few decades, modification of nucleoside/nucleotide analogues has been a field of keen interest to researchers due to their therapeutic properties for treatment of cancer, viral and microbial infections [1][2][3][4][5][6][7][8][9]. The very first cytotoxic

• chemotherapeutic agents used for the treatment of cancer were nucleoside analogues and nucleobases [10]. Azidothymidine (1, AZT) was the first approved drug for the treatment of human immunodeficiency virus (HIV) [11][12]. Subsequently, a large number of sugar modified nucleosides, such as ddC (zalcitabine) [13

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• biological activities [6][7]. Moreover, they can be used as starting substances for different heterocycles, as precursors for the synthesis of polymers, as potential pharmacons, for the synthesis of natural products or analogues, and also as building blocks in drug research [8][9][10][11]. Furthermore, some

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• . All cases will be covered throughout the text. Synthesis of 4-amino-β-naphthoquinones and analogues from β-NQS After the first discovery that β-NQS reacts quickly with amines to form colored products in good yields, this reagent became quite popular in quantitative analytical determinations of some

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of the three cleavage sites are blocked by the macrocycle. Accelerated molecular dynamics simulations verified a significantly higher degree of helicity for SMC stapled peptide P5 compared to the linear analogues P6 and aAxWt, which is in accordance with the experimental data obtained from CD and

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• , which leads to formyl products from formal oxidative cleavage of a C=C bond. Our interest in vinylogous analogues of 2-nitroaryl photoreactive groups stems from studies into alkenylboronic acid reagents for Chan–Lam-type modification of peptide backbone N–H bonds, directed by a proximal histidine

• . C–O cleavage, Figure 1A) through H-atom abstraction from a photoexcited intermediate, which produces an oxonium-type intermediate (in brackets). Hydrolysis of this intermediate then affords an alcohol product. Recently [16][17], we demonstrated that vinylogous analogues of this mechanism (Figure 1B

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• hoshinoamide A and other highly methylated polypeptide analogues. Our strategy was also helpful to further study its antimalarial activity. Structure-and-activity and functional studies with the fluorescent-labeled analogs are currently under investigation in our lab. Experimental General experimental

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• ]. In the same year, the Du group investigated the FeCl2·4H2O decarboxylative radical alkylative cyclization of cinnamamides 131/134 as an expedient approach towards dihydroquinolinone 133 and pyrrolo[1,2-a]indole 135 analogues in good yield and excellent diastereoselectivity (Scheme 27) [120]. In terms

A tribute to Carsten Schmuck

• Jochen Niemeyer,
• Ivo Piantanida and
• Thomas Schrader

Beilstein J. Org. Chem. 2021, 17, 2795–2798, doi:10.3762/bjoc.17.190

• into account particular features of “Carsten’s GCP” unit, or related analogues, he would propose several feasible structural modifications, which could provide novel properties of scientific interest. Finally, upon mutually agreeing on the next generation of new compounds, he would always take the