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

• – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only

• method is expected to significantly lower PEG synthesis cost. Keywords: base-labile; monodisperse; PEG; polyethylene glycol; protecting group; Introduction Polyethylene glycols and derivatives (PEGs) have found wide applications in many areas [1][2][3][4][5][6]. For some applications, polydisperse PEGs

• ]. Besides PEGs, similar approaches have also been used for the synthesis of oligosulfoxides [28]. In this article, we report the use of monomers such as 2 containing a base-labile protecting group with the phenethyl group for stepwise monodisperse PEG synthesis. With monomers having a base-labile protection

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• electron-poor phenol, was converted into the corresponding ether 2d only in traces (Table 2, entry 3). By using 3.0 equivalents of KOH, p-trifluoromethylphenol (1e) provided the product 2e in 48% yield (Table 2, entry 4). Also a phenol possessing a base-labile ester group (1f) afforded the product 2f in 47

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• . The treatment of the glycosylated tripeptides 6a–f and 7a–f with a mixture of TFA, DCM, and H2O (10:10:1) [31] afforded the partially deprotected acids 8a–f and 9a–f in quantitative yields. The final deprotection of both the base-labile acetyl and Fmoc-protecting groups was achieved by the treatment

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• other compounds in further reactions, e.g., click reactions or Sonogashira coupling. Systems for such reactions are tested with compounds 5 and 6. These compounds react in high yields up to 90%. The additional functional groups, which must of course be not base-labile survive the reaction conditions

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• conditions or heated ion exchange resin [21][22]. These methods are therefore not suitable for the alkoxylation of acid or base-labile substrates. To overcome the current limitations of reduction potentials of single electron transfer processes in photoredox catalysis we present herein a range of new N

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• in high chemical yield and purity by strategically introducing differentially protected dibasic amino acids such as lysine whose α- and ε-amino groups are protected as base labile Fmoc and trifluoroacetyl (Tfa) protecting groups, respectively. The whole concept is successfully illustrated using

• Mmt protecting group in the side chain of 9b from the chlorotrityl resin resulting in the detachment of the polypeptide chain 9b (Scheme 2). Therefore, we turned our attention to replace the acid labile trityl protecting groups with a base labile protecting group such as trifluoroacetyl (Tfa) as in

• the case of Fmoc-Lys-(Tfa)-OH amino acid. With the hope that introduction of a base-labile protecting group in lysine could provide the required solution, we began the synthesis of polypeptide chain 10 with Fmoc-Lys-(Tfa)-OH derivative (Scheme 3). This idea for the synthesis of polypeptide chain 10

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , as well as aliphatic chains. Unsurprisingly, esters and other base labile groups are not encountered. A recent publication by König and his group shows the DDQ catalysed (3DDQ Ered*(cat/cat•−) ≈ +3.18 V vs SCE) C–H amination of arenes and heteroarenes using weakly nucleophilic species such as

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• is incompatible with the standard deprotection treatment under basic conditions (generally aqueous ammonia) used to cleave other common base-labile acyl protection groups from nucleobases and release ON from the solid support. Furthermore, as the aqueous solubility of fully modified SATE

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• regime in which all of the sugar hydroxy groups have been protected with base-labile groups, most commonly acetate esters. Importantly glycosyl oxazolines are completely stable to the typical basic conditions used for ester removal (e.g., Zemplen deacetylation). The generally accepted approach (until

• 2009) was therefore to perform all protecting group manipulations/interconversions on the completed oligosaccharide to ensure that all OH groups were protected as base-labile esters, before oxazoline formation. In 2009, Shoda published [42] a paper that was to completely change the way in which

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• ]. Since then, several groups improved the chemical synthesis of capped RNA via solid-phase synthesis. The highly base-labile m7G moiety turned out to be a limiting factor because it is not compatible with standard solid-phase deprotection protocols. Due to its positive charge, the m7G moiety is

• ′-phosphorylated trimer synthesized by standard phosphoramidite chemistry. To address the problem of m7G instability under basic conditions, the TMG-capping reaction was carried out upon deprotection of all base-labile groups. Utilization of a novel, acid labile linker to the solid support allowed for subsequent

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• oligonucleotide. Since the phosphate protecting groups are normally base-labile and the repeatedly removable 5´-O protecting group is acid-labile, the 2´-O-protection should preferably be removable under orthogonal conditions. For this purpose, numerous protecting groups have been proposed [18][19], the fluoride

• phosphodiester linkage upon ammonolytical deprotection. In other words, the ODNs were used as PEG-conjugates in biological studies. In addition, a bifunctionalized PEG, bearing the acid labile DMTrO group at one end and a base labile Fmoc-NH functionality at the other end, has been used as a soluble support to

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• uncontrolled conditions are not suitable for natural molecules, as they are often characterized by different moieties bonded each other by thermo or acid/base labile ester bonds; nevertheless such report furnished us the proof of principle that the rapid rise of temperature due to MW can catalyse acetylation

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• was performed. The base-labile cyanoethyl group [51][52] is known to be resistant under synthesis conditions for the preparation of the phosphoramidite building block and for solid-phase oligonucleotide synthesis [49][53]. Building blocks compatibility with solid-phase synthesis of DNA single strands

• 55 °C. The Fmoc protecting group of oligonucleotide ON1 was removed, however, the cyanoethyl group as a base-labile protecting group of the thiol was not removed quantitatively from the oligonucleotide ON2 [54][55][56][57][58]. Dynamic template-driven assembly of double strand libraries

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• phosphates, its mild cleavage conditions and the possibility to directly conjugate the product after global deprotection via the amine functional group [28]. The presence of glucuronic acids in the oligosaccharide sequence precludes the use of a base-labile linker due to the risk of elimination reactions [30

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• smoothly with ≥95% coupling efficiency as determined by trityl assays. It was at the stage of the removal of the protecting groups to afford the free oligos that we encountered a severe problem with the adenine derivative. While the aqueous ammonia/methylamine base deprotection removed all base labile

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• , which was coupled with synthon 12 in anhydrous THF in the presence of 5-benzylmercapto-1H-tetrazole (BMT) as activator (Figure 5). The coupling product 16 was isolated with a yield of 28%. Finally, all remaining protecting groups were cleaved off. The base-labile β-cyanoethyl (CE) group was removed by

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• orthogonal to the base-labile Fmoc-group and can be cleaved by highly concentrated TFA solutions. In addition to these examples there is a number of diverse orthogonal protecting groups commercially available. They will have to be used, if peptides are modified additionally and they are cleaved under

• Nε-group of the lysine that should be modified, is protected specifically by a side-chain protecting group that is orthogonal to the Fmoc group. Acid-labile groups as Mmt [41] and Mtt (4-methyltrityl) [104] (classical cleavage with 1% TFA in DCM (dichloromethane)), base-labile groups as ivDde (1-(4,4

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• ] afforded linker 10. To support oligosaccharide synthesis, the safety-catch linker was first coupled to different resins (Scheme 2). In addition, since the activation and cleavage of safety-catch linkers is typically quite slow, a second, base-labile (Zemplén [24]) cleavage site was integrated to facilitate

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• conducted under an inert atmosphere; toluene is a favourite solvent and BINAP a commonly used ligand. Strong bases are required and water is added to dissolve them. Substituents in the starting material, which are base labile are not tolerated. With low catalyst loading and good availability of the

• hindered and functionalized aryl amines [22][23][24]. Aryl bromides are most frequently applied as substrates for the coupling of primary and cyclic secondary amines [17]. In the presence of a weak base such as caesium carbonate, many functional groups are tolerated, while NaOt-Bu has limitations when base

• -labile functional groups are present. Electron-neutral and electron-poor aryl bromides are suitable substrates [17], and ortho-substituents on the aryl halide are tolerated. In contrast, electron-rich aryl bromides give only poor results. Recently, the modular synthesis of indoles by a palladium

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• basic conditions of automated DNA phosphoramidite chemistry and/or DNA workup. We recently presented the postsynthetic incorporation of Nile Blue and a coumarin dye as representatives of base-labile fluorophores by the “click” ligation strategy [17]. Several other fluorophores (spanning the whole

• azide 4 of the base-labile phenoxazinium dye Nile Blue. The chromophore was incorporated as a DNA base surrogate using (R)-3-amino-1,2-propanediol as the linker between the phosphodiester bridges. Two DNA duplex sets were prepared with the phenoxazinium azide 4 (one set carried the chromophore in an A-T

Convenient method for preparing benzyl ethers and esters using 2-benzyloxypyridine

• Susana S. Lopez and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2008, 4, No. 44, doi:10.3762/bjoc.4.44

• acid-labile Boc group and the base-labile β-hydroxy ester. Minor modification of the above procedure renders it suitable for the formation of benzyl esters from carboxylic acids (Scheme 3). In order to avoid the potential for competing N-methylation of triethylamine, which is the optimal acid scavenger

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• groups. The ε-amino group of lysine and the γ-carboxy group of aspartic acid, involved in lactamization, were protected as the base-cleavable Fmoc amide and Fm ester respectively. After synthesizing the peptide chain and cleavage of the base-labile protecting groups, an efficient on-resin cyclization was