Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• cells was shown [37]. Thus, the hexyl and octyl derivatives 25a,b showed the best PCE values of 5.1 and 5.2%, respectively, which is higher than analogues bearing a longer or branched hydrocarbon chain (Scheme 15 and Table 5). If the OSC active layer is prepared with the addition of diiodooctane, the

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• + antagonist, and exhibits promising anti-oxidant properties. 4-Phenyl-2-propionamidotetralin (4-P-PDOT, 3, Figure 1) [5] is a melatonin MT2 selective antagonist that can be used to map melatonin receptor subtypes in tissue and serves as a chemical biology tool to identify sub-type selective analogues with

• methods generally require multiple steps, proceed in low overall yields, and have a limited ability for structural modifications to prepare analogues with new substitution patterns for enhancing activities. Consequently, it is highly desirable to develop new synthetic methods that provide efficient access

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

• neurotoxin, which is an eosinophil secretion protein and a member of the Ribonuclease A (RNase A) superfamily [36]. Double-headed nucleosides were also found to be active against orthopox viruses, vaccinia virus, and cowpox virus under in vitro conditions [11], whereas few double-headed nucleoside analogues

• analogues 89a and 89b with 2,6-dichloropurine under acidic conditions resulted in the formation of mononucleoside analogs 90a,b. The nucleoside 90a was reacted with mesitylnitrile to give the double-headed nucleoside 91, whereas nucleoside 90b was reacted with phenylazide to give the double-headed

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• fragrances whose production involve aldol reactions as key steps. Chapuis et al. have described, several methods for the synthesis of methyl dihydrojasmonate (33) and other α-substituted cyclopentanone analogues [92], in addition they also performed α-functionalisation of the cyclopentanone ring via an aldol

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

• derivative 57 in 72% combined yield (Scheme 18) [88]. In 2020, Pierce and co-workers developed a method for the synthesis of guanidinium alkaloid batzelladine D in enantiomeric and racemic form, along with a series of stereochemical analogues. The batzelladines are a family of polycyclic guanidinium

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• biomedical applications due to their ability to inhibit the glycan and glycosaminoglycan biosynthesis [34][35][36][37]. The fluorine substituent has typically been introduced into these GlcNAc and GalNAc analogues using nucleophilic fluorination. The primary position (C6 hydroxy group) was fluorinated by

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• apoptosis [1][2][3][4][5][6][7]. Due to its involvement in a wide range of cellular processes, significant efforts have been made in the last two decades targeting sphingosine analogues signalling as a therapeutic strategy. For instance, FTY720-P (3), the phosphate of FTY720 (2, fingolimod), proved to be a

• the lack of a readily available natural sources and the high biological importance of sphingolipid analogues, their synthesis has been the subject of numerous studies [16]. The key step for the synthesis is the stereoselective construction of the 2-amino-1,3-diol moiety of the molecules. Generally

• , two main synthetic strategies are used to prepare these analogues. One requires the insertion of the alcohol and amino groups in the α,β position with the correct stereochemistry [17][18][19][20]. The second strategy involves a bond formation between two chiral centers to produce the targeted 2-amino

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• . Electrophilic substitution and further condensations give polycyclic systems, including oxazolo- and chromeno-fused analogues. Keywords: benzofuropyridines; benzoquinones; dibenzofurans; Meerwein reaction; metal-free synthesis; Introduction Dibenzofurans are important oxygen-containing heterocycles present in

• multiple natural products [1][2] and have broad applications in areas ranging from medicinal chemistry [1][2][3][4][5][6][7][8][9][10] to materials science [11]. Figure 1 presents a few examples of dibenzofuran-containing molecules. Benzofurocoumarin analogues of 1 have antiproliferative effects on human

• dibenzofurans 4 were also explored for the treatment of various skin diseases [16]. Furthermore, 2-substituted benzofurobenzofurans 5 with antitubercular activity have been reported [17]. Prado et al. reported the antimycobacterial activity of furo[3,2-f]chromene analogue 6 [18]. The aza analogues of

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• ). The armed benzyl-protected glycosyl fluorides α-15 and 16 were more reactive than their acylated analogues and the corresponding glycosides 17 and 18 were obtained at lower temperatures (Scheme 4). The reaction temperature for mannosyl fluoride α-15 was optimized to 30 °C (Table S5, Supporting

• glucosyl fluoride gave better yields (18a and 18d) than with the corresponding acylated analogues β-9 and α-11 described above. It was also found that the glycosylation stereoselectivity with glucosyl fluoride 16 did not depend on the anomeric ratio of glucosyl fluoride 16: both anomers of 16 yielded

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• . This modification is achiral at the phosphorus atom (Figure 1C), and thus, unlike the phosphoromonothioate (PS) analogues (extensively covered in other reviews [18][42][87][88]), the synthesized oligonucleotide is stereochemically pure. This simplifies their purification, as there is no longer the need

• (R) or (S) starting material, respectively. These simple nucleic acid building blocks were first synthesized in 1971 by Ueda et al. [96]. The group was able to synthesize adenine, cytosine, and uracil GNA analogues by reacting these bases with glycerol α-chlorohydrin or glycidol. The following year

• , the Seita group showed that thymine and guanine analogues could be prepared in a similar fashion [97]. Interestingly, both groups found that condensation of purine bases to yield GNA derivatives gave two dihydroxypropylated isomers: the N3 (I) and the N9 (II) dihydroxypropylated isomers. Using

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

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• purposes. Recently, a proliferation of methods has allowed easy access to a particularly desired class of these compounds: singly fluorinated compounds such as fluoromethyl ethers [1]. Still missing from the chemist’s toolkit, however, are means to construct their more highly oxidized analogues

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

• 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

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• ]. The major challenge in designing chemically modified ONs as antigene/antisense agents is to ensure an efficient cellular uptake and nuclease resistance while still maintaining, or ideally increasing, binding affinity and specificity of the ONs towards their DNA or RNA target. Many synthetic analogues

• of natural ONs, such as peptide nucleic acids (PNA) [20], locked nucleic acids [21] (LNA, also known as bridged nucleic acids (BNA) [22]) and phosphorothioate (PS) ONs [23][24] have been evaluated for antigene/antisense applications, however, each of the analogues did not meet all the requirements

• the factors that determines the thermodynamic stability of nucleic acid secondary structures. Neutral or positively charged oligonucleotide analogues should bind more tightly with complementary DNA or RNA. Several studies have focused on the introduction of positively charged groups to a nucleobase

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• promising. They are synthesized in two main reactions: nucleophilic cyclopropanation according to the Bingel method and thermal addition of diazo compounds. This present review summarizes the material on the synthesis of monofunctionalized methanofullerenes – analogues of [60]PCBM – based on various diazo

• compounds. The main cyclopropanating agents for the synthesis of monosubstituted methanofullerenes, the optimal conditions and the mechanism of the [2 + 1] cycloaddition, as well as the practical application of the target products are analyzed. Keywords: [2 + 1]-cycloaddition processes; analogues of [60

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

• Anuj Kumar Chhalodia Jeroen S. Dickschat Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany 10.3762/bjoc.17.51 Abstract Two analogues of 3-(dimethylsulfonio)propanoate (DMSP), 3-(diallylsulfonio)propanoate (DAllSP), and 3

• -(allylmethylsulfonio)propanoate (AllMSP), were synthesized and fed to marine bacteria from the Roseobacter clade. These bacteria are able to degrade DMSP into dimethyl sulfide and methanethiol. The DMSP analogues were also degraded, resulting in the release of allylated sulfur volatiles known from garlic. For unknown

• responsible for the demethylation activity [28]. Also the labelling from (34S)DMSP was efficiently incorporated into DMDS and dimethyl trisulfide (DMTS) [29]. Our previous investigations have also demonstrated that synthetic, i.e., non-natural DMSP analogues such as 3-(ethylmethyl)sulfoniopropanoate (EMSP), 3

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• Jiaxi Xu State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China 10.3762/bjoc.17.41 Abstract Phosphonodepsipeptides are phosphorus analogues of depsipeptides

• and phosphonate-linked analogues of naturally occurring peptides. They are more stable than phosphonopeptides and have been widely applied as enzyme inhibitors, haptens for the production of antibodies, biological agents, and prodrugs. The synthetic strategies towards phosphonodepsipeptides are

• phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids. Keywords: alkylation; mimetic; multicomponent condensation; peptide; phosphonopeptide; phosphonodepsipeptide; phosphonylation; Introduction Both, phosphonopeptides and phosphonodepsipeptides are phosphorus analogues of peptides [1][2][3][4][5]. The

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

• substitution of the proline residue with fluorinated analogues (fluoroprolines, Figure 1) creates an option for making fluorine a component of a living organism. Fluoroprolines were found to be generally compatible with the cellular machinery, in particular the one that transports them inside the cells and

• in cellular biochemistry and the potential of fluoroprolines to fulfill them. Here, by fluoroprolines, we will only refer to 4-monofluoroprolines and 4,4-difluoroproline, which are the best biochemically characterized proline analogues (Figure 1). Many other fluorinated proline analogues exist, as

• analogous structures. Most typical among proline analogues would be hydroxy-, fluoro-, alkyl-, dehydroprolines, analogues having ring size variations, and N-alkylamino acids (Figure 2C). To clearly discriminate the alanine and proline-based architectures, we recently proposed to call this set of structures

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 6-O-analogues are less common [61]. Azolylpurine derivatives are important due to their potential as drug candidates. They can be used as agonists and antagonists of adenosine receptors [58][64][65][66] and against Mycobacterium tuberculosis [60]. They also show useful fluorescent properties [11][67

• hydrogen bond. This is supported by a smaller deviation of the C(2’’) chemical shift value (61.7 ppm) in comparison to the theoretical shifts for a Csp2 centre. Similar structural analogues are known in the literature [54][83][84][85] but their structural analysis was incomplete. As the aforementioned

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

• nonfluorinated analogues (Eox (PhNMe2) = +0.71 V (SCE)), the radical cation 180 is formed under the reaction conditions, and deprotonation at the methylene unit near the CF3 group is highly favored because of the higher acidity, accounting for the observed high regioselectivity. In addition, the transient

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

• introduction of unnatural amino acids into proteins have been reviewed extensively elsewhere [5][6][7] and here we will only discuss the most recent advances. The chemical structures of a selection of 19F-labelled amino acid analogues that have been utilized in 19F NMR studies in chemical biology are shown in

• , all peptides where 8 was introduced could be detected even at concentrations as low as 5 μM, demonstrating that pFtBSer is a highly sensitive tool to study binding events by way of 19F NMR chemical shift and nuclear relaxation changes. In addition to homoserine, perfluorinated analogues of both

• the aforementioned issues, Virta and co-workers have explored the application of trifluoromethyl analogues of guanosine, cytidine and uridine based in 2’-O-[(4-trifluoromethyltriazol-1-yl)methyl] reporter groups as 19F NMR probes for the detection of RNA secondary structures (Figure 14). As shown by

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• mirror those observed for their Type I analogues; however, the HOMO and LUMO values in the Type II emitters are more stabilized and the energy gaps are reduced. The HOMO of 5CzBN is symmetrically distributed across the ortho- and meta-disposed carbazoles while the HOMO of 5CzTRZ is located mostly on the

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• activity was observed for cyclam–gold complex 6a-Au(III) versus the open cyclam analogues 5a-Au(III). Complex 5a-Au(III) afforded a full conversion in the alkyne carboalkoxylation in 5.5 hours, compared to in 24 hours for complex 6a-Au(III) (Table 1, entries 1 and 2). The same trend was observed for Au(III

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• groups (SRF, RF = CnF2n+1) have received comparatively little attention despite promising applications in liquid crystal displays [13][14], as pharmaceuticals and agrochemicals [15]. For example, analogues of the drug losartan featuring SC2F5, SC3F7 and SC4F9 groups have shown promise as treatments for