Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -butynoate successfully generated the metal-bound heterocyclic complexes. The alkylation reaction of 171a led to the bond cleavage between ruthenium and nitrogen to produce several 1-alkylated 4,5-bis(ethoxycarbonyl)-1,2,3-triazoles 172 [66]. Herein, the sodium azide initially reacts with [Ru]–Cl 168 to

• produce [Ru]–N3 169. Then, the resulting intermediate cyclizes with ynoate ester 170 to form metal-bound heterocyclic complex 171. This metal-bound heterocyclic complex 171 reacts with alkyl halide to produce final product 172 via a bond cleavage between ruthenium and nitrogen (Scheme 45) [66]. Cu/Ru

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• -pyridylhydrazide allowed for domino C–H/N–H functionalization. The approach featured remarkable functional group compatibility and ample substrate scope. Thereby, highly functionalized aromatic and heteroaromatic isoindolin-1-ones were accessed with high efficacy with rate-limiting C–H cleavage. Keywords

• also proved to be a viable substrate. Thus, the corresponding isoindolone 3aa was assembled via a tandem decarboxylative C−H/C−C sequence (Scheme 3a). The practical relevance of our approach was reflected by the cleavage of the N-2-pyridylhydrazide group, yielding S-3aa (Scheme 3b). Inspired by the

• -position of the reisolated benzhydrazide 1c and product 3ca when the reaction was conducted with the isotopically labeled D2O as cosolvent (Scheme 4c). This observation indicated that the C−H cleavage is irreversible. In accordance with this finding, a kinetic isotope effect (KIE) of kH/kD ≈ 6.1 was

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

• addition products 10 and 12 (Scheme 7A). In both cases, a low diastereoselective control was observed. Control experiments revealed that, under these reaction conditions, the hydroalkylation was reversible (Scheme 7B), indicating the participation of the silver salt in the C(sp3)–C(sp3)-bond cleavage

• hydroalkylation product 92e’, indicating a possible double bond isomerization under these reaction conditions. The postulated mechanism starts with the generation of an ethyl radical from BEt3. This radical then acts as a radical initiator to promote the homolytic cleavage of the carbon–halogen bond of the α-EWG

• carried out between 96 and completely deuterated cyclohexane 96-d12. A considerable decrease in the reaction yield was observed when the reaction was carried out in the presence of radical trapping reagents (Scheme 37B). Based on these observations, the C(sp3)–H homolytic bond cleavage appears to be the

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

• thermal cleavage of Boc groups [42]. Without studying the main characteristics of the OSCs, they showed that after annealing the mixtures of these polymers with PC61BM at 200 °C, the surface morphology becomes highly inhomogeneous, with the presence of a large number of crystalline domains. In contrast to

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

• oligonucleotides [42]. Pedersen and Nielsen [35] synthesized a double-headed nucleoside with two different nucleobases, i.e., 2′-deoxy-2′-(thymine-1-yl)ethyluridine (11) (Scheme 3). The oxidative cleavage of the allyl group in TIPDS-protected 2-allyl-2-deoxyuridine 8 gave the TIPDS-protected hydroxynucleoside 9 as

• 116 following previously reported procedures [65]. Then, the nucleoside 116 was converted into the primary alcohol 117 by treatment with OsO4 and oxidative cleavage by NaIO4 followed by reduction using NaBH4. The primary alcohol 117 was further converted into nucleoside monomer 118 by introduction of

• mixture of E/Z isomers. Further, double bond cleavage of nucleoside 120 followed by benzoylation produced the benzoic acid ester of the hemiacetal analogue 121 which was finally converted into double-headed nucleoside 122 via Vorbrüggen coupling reaction followed by deprotection using methanolic ammonia

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

• of alcohol byproducts confirmed the homolytic nature of the bond cleavage at C-4 and served to assess the half-life of the alkyl radical generated. To this purpose, the reaction of dicyanoglutarimides bearing a radical clock substituent (cyclopropylmethyl or 5-hexenyl) was investigated. The reaction

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

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• (Scheme 7d). These results indicate a large primary isotope effect, which suggest that the C(sp3)–H bond cleavage of acetonitrile contributed to the rate-determining step. Based on the present results and the literature [18][19][20][21][22][23][24][25][26][31][60], the reaction pathway is proposed as

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• is, probably, a result of a transamidation reaction upon the treatment with a base, for example, alkoxide anion. The nucleophilic attack of the alkoxide anion leads to the cleavage of the C(7)–N(8) bond to form intermediates B and C followed by the recyclization of the thiazolidine ring involving the

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

• C2, can be accomplished by nucleophilic fluorination and azidolysis starting from dianhydro derivatives 1 and 2 as we described previously [26]. The resulting intermediates 3 can be transformed into 2-azidohexopyranosides 4 by cleavage of the internal acetal and protection of the anomeric position

• deoxyfluorination, which would likely occur with the β-anomers of 14–19 [41]. The complete separation of the α-anomer by conventional silica gel column chromatography was possible for thioglycosides 14, 16, 17, and 19, while the products 15 and 18 were obtainable as enriched α-anomers (α/β ≥ 3.3:1). Cleavage of the

• internal acetal with PhSTMS was accompanied by the formation of low quantities of side-products detectable by TLC and separable by careful chromatography except for the cleavage of 12 where the side products co-eluted with the fraction containing the β-anomer of the product. In the case of the cleavage of

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• Minnaard group reported a protocol for the addition of boronic acids to enones [37]. At first, they tested the combination of Pd(OAc)2 with triflic acid (TfOH) to obtain a Pd(II) complex with a weakly coordinating anion that is necessary for a fast Pd–C bond cleavage and thus avoiding the undesired β

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

• We started our study by short screening of the glycosylation conditions in liquid SO2 (Table 1). To avoid a potential cleavage of acid-labile protecting groups and to obtain an easily analyzable reaction mixture, pivaloyl-protected mannosyl fluoride α-1a as a relatively stable disarmed glycosyl donor

• basic nitrogen or fluorophilic trimethylsilyl group in the molecule of the glycosyl acceptor (Figure S1, Supporting Information File 1). To our delight, no cleavage of the pivaloyl protecting groups in liquid SO2 medium was observed and the main side-product formed in the series of mannosides 3 was the

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

• complementary RNA were substrates of RNase H, with greater cleavage of the RNA strand observed for the latter, demonstrating the gene silencing potential of these analogs [183][186]. Uniformly modified phosphorothioate (PS) FANA forms a duplex with RNA with a higher Tm relative to the PS-DNA/RNA duplex, however

• , RNase H-mediated cleavage of RNA was diminished for the duplex formed with PS-FANA relative to PS-DNA [187]. Improved cleavage by RNase H was observed with chimeric PS-FANA/DNA [187]. PS-FANA/DNA chimera with either flanked or alternating segments of FANA residues, as demonstrated by knockdown of c-MYB

• incorporated into a DNA/RNA hybrid duplex it was shown to decrease the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage [208]. In 2018, the work was expanded to include 2',4'-diOMe-rU, 2'-OMe,4'-F-rU, and 2'-F,4'-OMe-araU nucleosides (Figure 9E,F,G) [209]. This work

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• no need for additional reactions after cleavage [27][28][29]. One approach to generate LNP formulations with higher specificity for antigen-expressing cells is to use RNA aptamers. RNA aptamers are short oligonucleotides that are evolved using a process called systematic evolution of ligands by

• . Coupling of Fmoc-Dap(Fmoc)-OH and Fmoc deprotection were carried out as described above. To ensure the complete lipidation of the two free amines of Dap, 8 equiv of palmitic acid, 8 equiv of HATU, and 12 equiv of DIPEA in DMF were used. Cleavage of the peptide–lipid conjugates from the solid support and

• removal of the side-chain protecting groups was achieved by using trifluoroacetic acid (TFA)/phenol/water/triisopropylsilane (TIPS) 88:5:5:2 (3 × 60 min). After cleavage, the remaining resin was extracted with DCM (2 × 10 min). All DCM extracts and TFA cleavages were combined, and the resulting mixture

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• homolytic cleavage of the weak Br–N3 bond in bromine azide [54][55]; (3) the bromine radical can also be generated from NBS with the formation of a succinimide radical; (4) alkyl radical intermediate A is then formed via hydrogen abstraction by the succinimidyl radical and/or azidyl radical [56][57]; (5

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• Innovation, Faculty of Agriculture, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan 10.3762/bjoc.17.72 Abstract The homolytic cleavage of the PV(O)–PIII bond in tetraphenyldiphosphine monoxide simultaneously provides both pentavalent and trivalent phosphorus-centered radicals with different

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

•  27). It is worth noting that EDA complex has been firstly employed for the generation of alkoxy radicals under visible-light irradiation, achieving selective C(sp3)–C(sp3)-bond cleavage and allylation or alkenylation. In 2017, Li and colleagues [57] reported a reaction for the synthesis of

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , the enol form of 1,3-dicarbonyl 2 attacks the sulfonyl group in 1 to form intermediate I which later undergoes proton transfer to form intermediate II. Cleavage of the N–S bond in intermediate II generates the β-O-tosylcycloalkenone 4 and triazolyl anion III. Subsequent counter-attack of the triazolyl

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• trans-12b can be also easily deprotected by a rhodium-catalyzed isomerization to the corresponding N-propenyl lactam followed by osmium tetroxide-catalyzed oxidative cleavage, providing lactam trans-17 in 62% yield. Additionally, the diastereomeric mixture of lactam 12o was subjected to oxidative N–O

• bond cleavage by mCPBA furnishing bicyclo[3.3.0]octandiones 18. The isolation of a mixture of four diastereomers as in the starting material indicates that radical coupling by TEMPO proceeds with exclusive diastereoselectivity (vide infra). Discussion The sequence nucleophilic epoxide opening/Brook

[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

• processes, among which reactions leading to methanofullerenes are widely used. Two main synthetic methods for the production of methanofullerenes can be distinguished (Scheme 1): nucleophilic cyclopropanation with stabilized carbanions that occurs by the addition–cleavage mechanism – the Bingel reaction (I

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• oxidation, cross-linkage, bond cleavage). The term “biodegradation” indicates a “degradation caused by enzymatic processes resulting from the action of cells”. Although commonly used, also for artificial polymers, the term “biodegradable” specifically refers to biorelated polymers (i.e., proteins, nucleic

• acids, polysaccharides), which are "susceptible to degradation by biological activity by lowering of the molar masses of macromolecules". Therefore, in this situation, “chain cleavage” and “degradation” are used interchangeably. To avoid confusion, instead of “(bio)degradation”, in the present review

• and a 20:1 excess of strong base potassium tert-butoxide as cocatalyst (Table 1, entry 1) [183]. Although the reaction mechanism was not investigated in detail, it was suggested that cleavage of the ester linkage may occur in a concerted manner through the reported heterolytic route [184][185]. The

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• chemistry and synthetic biology. Stereo- and regioselective hydroxylation at C9 (steroid numbering) is carried out using whole-cell biocatalysis, followed by the chemical cleavage of the C–C bond of the vicinal diol. The two-step method features mild reaction conditions and completely excludes the use of

• ][4]. A more challenging synthesis of secosteroids with unique broken tetracyclic carbon skeletons and abeo-steroids with migrated bonds has received attention only recently [5][6]. As the bond cleavage may occur at the 5,6-, 9,11-, 9,10-, 8,9-, 8,14- or 13,17-positions (Figure 1A), the selection of

• approach to 9,11-secosterols is depicted in the retrosynthetic analysis in Scheme 1. There are two key steps in obtaining the skeleton of the secosterol. The first is (di)hydroxylation at C9 (C11), and the second is C9–C11-bond cleavage, which can be carried out by a well-developed chemical oxidation of

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• was stepwisely elongated, and eventually conjugated with the (perfluoroalkyl)ethyl acids (Scheme 2). After the cleavage from the resin, the Fmoc groups of the amino acids were removed, and the F-lipopeptides were purified using a dialysis membrane. According to mass spectrometry, FTIR, and HPLC

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

• demethylation pathway by action of the enzymes DmdABCD to methanethiol (MeSH, Scheme 1A) [12] or through lysis by DddD [13] or hydrolytic cleavage by one of the known DMSP lyases (DddW [14], DddP [15], DddQ [16], DddL [17], DddY [18] or DddK [19]) to dimethyl sulfide (DMS, Scheme 1B). It has already been