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

• –Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to

• Supporting Information File 1, Figure S4). As a conclusion from those experiments, it was hypothesised that the linker might be too rigid resulting in a distorted structure, which has also been previously reported for thioether cross-linked cysteines bearing a biphenyl template within the staple [20]. Hence

• , a linker with a higher degree of flexibility was designed. This goal was achieved by a modification of amine-containing amino acids in the i + 4 position through coupling to 4-carboxyphenylboronic acid, followed by intramolecular SMC. Different linker lengths were achieved by introducing ʟ-2,4

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• protecting group or cleaving the linker under more basic conditions is not common. In contrast, the use of acid-labile protecting groups or linkers involving carrying out reactions under less acidic conditions and removing the protecting group or cleaving the linker under more acidic conditions is more

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• both cryogels and ceramics into a mould, and a physical cross-linker was used to realise the drug theophylline after stimuli had been achieved. Due to the layer system, drug release could occur without diffusion of the subsequent layers, controlling the speed of the release in the ceramic cryogel. In

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• backbone, resulting in the blue shift of absorption bands (λmax around 350 nm). Interestingly, the ethynyl linker in 17 was assisting the effective delocalization despite the presence of the n-alkyl group at position 6, as evidenced by its large red-shifted absorption at 456 nm compared to 19. The

• -polyazulenes 45 containing a thienyl linker. Synthesis of azulene-bithiophene 48 and azulene-benzothiadiazole 52 copolymers. Conditions: (a): (i) Na2CO3, Aliquat 336, Pd(PPh3)4, 100 °C, toluene, 90% (ii) NBS, CHCl3/HOAc, −10 °C, 83%, (b): Na2CO3, Aliquat 336, Pd(PPh3)4, toluene, 110 °C, 9%, (c): Na2CO3

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• (e.g., Fmoc and Lev) [269][280][281]. These compounds could be prepared entirely on a solid support, or following a solution-phase fragment (or block) coupling. In this case, the branch produced by AGA, employing a traceless linker [118], was converted into a glycosyl donor and coupled to the mannan

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• ], and the triazole-linker variant carrying three cationic charges (57) [95] stabilized the formed triplex by 28.0 °C and 30.5 °C, respectively [94][95]. These cationic 2’-amine-functionalized LNA modifications (51–57) all gave high binding affinity towards RNA with excellent nuclease resistance, making

• shielding mediated by the salt ions [106]. Additionally, this class of ONs showed high resistance towards nuclease-catalyzed degradation [106]. Subsequently, two variants of this phosphoramidate linker strategy were synthesized, one being the N,N-(dimethylaminopropyl)phosphoramidate linkage (monomers 73 and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• [104]. The manganese(I)-catalyzed intermolecular alkenylation of tryptophan-containing peptides 32 was performed under basic conditions, yielding hybrid peptides 34 without racemization, containing a trans-alkene linker bearing biologically active motifs in chemo- and site-selective manners assisted by

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

• (Figure 2B). An innovative design links the two ends together with an ethylene glycol linker (Figure 2C), which reduced the unfavorable loss of entropy by converting the binding event from a trimolecular to a bimolecular process [34][35][36]. The new bis-PNAs (Figure 2C) showed about two orders of

• connected E to the PNA backbone with a linker two atoms longer than in standard PNA, which was suggested to circumvent the 5-methyl group of thymine and enable hydrogen bonding to the 4-oxo group [110]. More recent work [111] has questioned the originally proposed hydrogen bonding scheme shown in Figure 7

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

• acceptor anchor units. Nonfullerene OSC based on perylene diimide-derived isoindigo. Isoindigo as an additive in all-polymer OSCs. Bisisoindigos with different linker structures. Nonthiophene oligomeric monoisoindigos for OSCs. The simplest examples of polymers with a monothienylisoindigo monomeric unit

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• to explore the synthesis of a ᴅ-manno C6-tetrazole thioglycoside donor and examine subsequent installation of C1 phosphate and anomeric linker groups. Results and Discussion An initial route towards a protected C6-tetrazole building block started from known mannuronic acid thioglycoside 1 (Scheme 1

• overall yield for the route increased from 9 to 21%. To demonstrate capability for anomeric linker attachment and conversion to a biologically relevant analogue of mannuronic acid 1-phosphate, 3-aminopropyl glycoside 20 and glycosyl 1-phosphate 21 were synthesised (Scheme 4). The mixture 18/19 was used

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

• attached directly to the sugar or via a linker. Further modifications were introduced by the substitution of some of the naturally occurring nucleobases by halogens or alkyl groups. On the other hand, a variety of heterocyclic/carbocyclic moieties were considered as the head of these modified nucleosides

• attached to the anomeric carbon of the pentofuranosyl/hexopyranosyl sugar moiety and an additional nucleobase/heterocyclic/carbocyclic moiety attached either directly or through a linker to any carbon of the sugar moiety either by C–N or C–C bonds. However, in case of base to base double-headed nucleosides

• , the additional nucleobase/substituent or unsubstituted phenyl moiety/polyaromatic moiety/carbocyclic moiety/heterocyclic moiety is attached to the first nucleobase with/without a linker. Whereas, all the acyclic double-headed nucleosides had natural nucleobases or heterocyclic moieties attached at 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

• moieties, such as a tetrose (ʟ-α-threofuranose, TNA [48]), and hexoses (e.g., hexitol, HNA [49]; altritol AtNA [50]; xylol XyNA [51]), or cyclohexene (CeNA [52]), a morpholino moiety (PMO [53]), and an acyclic, chiral glycol linker (GNA [54]), to generate so-called xeno nucleic acids (XNAs [55][56]). In

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

• Hope (Duarte, CA). The RNA aptamers, A-1 [35] and G-3 [34], were developed by Dr. Jiehua Zhou at City of Hope (Duarte, CA), and include the addition of a 3 carbon linker (XXXXXX), a sticky-bridge motif, and a 3’ amino linker C6, 3aminoC6, at the 3’ end. Annealing of the Cy5 DNA oligonucleotide to the

• columns. Initially, fluorenylmethyloxycarbonyl (Fmoc) group removal from the Rink linker was achieved by applying 20% piperidine in DMF (2 × 30 min). Preactivation of Fmoc amino acid (4 equiv) prior each coupling was performed with 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• -hydroxyisovaleric acid-derived spirophosphoranes as the phosphorus reagents [57]. By using a similar strategy, linker-linked bisphosphonodepsidipeptides were synthesized [10]. The current method is also an interesting synthetic strategy of phosphonodepsipeptides. It can realize an asymmetric synthesis of

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• the described reactivity would be observed with substrates not containing a ketone linker. Replacing the ketone moiety with an oxygen or sulphur atom proved unsuccessful, with only complex mixtures being obtained the upon treatment with AlCl3 (see Supporting Information File 1). This observation

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• ferulate to the primary hydroxy group of α‐ʟ‐arabinofuranosides. Moreover, a novel feruloylated 4-nitrocatechol-1-yl-substituted butanetriol analog, containing a cleavable hydroxylated linker, was also synthesized in 32% overall yield in 3 steps (convergent synthesis). The latter route combined the

• that obviates the need for a glycosyl moiety while containing a cleavable hydroxylated linker that mimics the natural geometry and physicochemical properties of glycosidic linkages. Results and Discussion Chemoenzymatic synthesis of 5-O-feruloylated α-ʟ-arabinofuranosides The synthesis of the

• ) displaying a hindered electron-withdrawing group. This led to a low target product yield (i.e., 5, 6, 8, and 9), a lower reactivity, and/or a higher hydrolysis of the vinyl ferulate into ferulic acid. Synthesis of ʟ-arabinofuranoside-free 4-nitrocatechol-1-yl–linker–ferulate chromogenic substrate 12 and

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• stereochemistry as catalysts [27]. The stereochemical properties were sensitive to the linker size and length, and the yield of the syn-head-to-tail-9,10:9',10'-cyclodimer could reach 97–98%. Traditional thiol-functionalized organic ligands decorated on the surface of gold nanoclusters (AuNCs) tend to generate a

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• -complementary [14] binding units (BU, blue) and a connecting linker unit (LU, green) to connect the BUs. In this case, the BUs are ureidopyrimidone units, which dimerize due to a fourfold hydrogen bond, thus allowing for strong supramolecular interactions [15]. Due to the flexibility of the LUs, the BUs can

• Meijer, we now developed a series of novel ditopic monomers as potential VIIs. We conducted a systematic variation of both the linker unit and the binding unit in order to investigate structure–property relationships with regard to VII performance and solubility in nonpolar solvents (such as motor oils

• BUs via the amino group should result in the necessary concave prearrangement [28]. Force field calculations, carried out in order to determine the optimal distance between LU and BU (see Supporting Information File 1, chapter 8), show that a propionamide is the shortest linker that allows for

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• ]. The attachment of pyrenes to the termini of a flexible peptide linker results in a ratiometric fluorescent probe (Figure 1C). Upon interaction with a biomolecule, the distance between the pyrenes changes, subsequently their monomer to excimer and vice versa fluorescence signal changes. However, the

• ) [42]. Probe 6 has a central lysine spacer which is connected to two symmetric peptidic arms. Each arm contains a cationic lysine as a positively charged head group and a pyrene moiety at the end of the γ-aminobutyric acid linker. Compound 6 is mostly in folded conformation in solution and emits pyrene

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• linker. The solvent-free protocol includes the use of a lower amount of azide 2d,c,f (2.5 equiv) in comparison with the reaction in n-propanol (4 equiv of azide) to afford the desired products in the same yield and therefore was selected as the method of choice for the synthesis of 3aj–an (Scheme 6). The

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• using an ATP-loaded agarose gel obtained from Sigma-Aldrich (cross-linked 4% beaded agarose, ATP is attached at its C8 position via a 9C linker, 1–5 μmol ATP per mL gel). For the binding assay, 5 nmol DNA in 200 μL column buffer (300 mM NaClO4, 5 mM Mg(ClO4)2, 20 mM MOPS (pH 7.4)) were loaded onto 500

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• synthesized a number of pyrimidine and purine derivatives carrying amino linkers of different length and flexibility [13][20]. Linker-modified uridine derivatives, upon conversion into phosphoramidite building blocks, were incorporated in RNA and used for a systematic study of distance determination of

• nucleic acids via Förster Resonance Energy Transfer (FRET) [20]. More recently, we started an effort to develop an efficient strategy for the preparation of a linker-modified adenosine building block, which in a future project is to be used for post synthetic conjugation of reporters or functional

• phosphoramidite building block 9 (Scheme 2). Results and Discussion Typically, the synthesis of C8-alkynyl derivatives relies on C8-bromoadenosine as reactant for the Sonogashira cross-coupling reaction to introduce the amino linker N-(propyn-2-yl)-6-(trifluoroacetamido)hexanamide (L) bearing an alkynyl moiety

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• units as the metal-coordination units (Figure 9a). When the ligand 20 was mixed with Fe2+ or Zn2+ ions, the tetrahedral cage complexes [M4(20)12]8+ were formed quantitatively. The flexibility through a methylene linker in 20 allowed the formation of the S4-symmetric cages [Fe4(20)12]8+ or [Zn4(20)12]8

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of

• ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand–G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily

• . With this background, we proposed that the functionalization of the berberine scaffold with adenine-appended alkyl substituents may provide a useful platform to further explore this important aspect. Specifically, we wished to examine whether adenine–berberine conjugates with a varying linker length