Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• (Figure 2), and assay buffers containing high concentrations of Mg2+ ions [15]. When advances in automated solid-phase synthesis made oligonucleotides of any given sequence readily available [16], copying reactions involving the extension of a primer bound to a specific sequence of hairpins mimicking this

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

• partially 2’-O-masked with PivOM groups were synthesized via a solid-phase method involving silyl-based protections on amino functions of the nucleobases combined to CNE on phosphates and Q-linker between pro-RNA and the solid support [48]. One of them with five PivOM groups at the 5’-end was active in a

• available unmodified ONs, while the second approach first requires the synthesis of a modified unit followed by its incorporation into ON during solid-phase synthesis. However, the first approach is far less efficient than the second one because the labeling of phosphodiester linkages with diazo compounds

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• of potentially successful candidates. This purpose is best achieved by the usage of trinucleotide synthons for codon-based gene synthesis. We here review the strategies for the preparation of fully protected trinucleotides, emphasizing more recent developments for their synthesis on solid phase and

• allows the preparation of the trinucleotide, its conversion into a coupling competent building block, and its subsequent use in chemical DNA synthesis. Trinucleotides have been prepared in solution [19], on solid phase [20], and more recently on soluble polymers [21][22][23] (Figure 1), followed by

• . Preparation of trinucleotides on solid phase Given the fact that trinucleotide synthesis in solution requires tedious purification and isolation of the products after each step of the synthesis, the assembly of trimers on a solid phase appears to be an attractive alternative. However, it has to be taken into

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• unbound probes, which is most commonly achieved by solid phase hybridization followed by washing to eliminate the unbound probes before performing the fluorescence readout. These assays require multiple steps, and so are time-consuming making them unsuitable for real-time monitoring, such as nucleic acid

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• sodium methoxide in MeOH, which yielded the free nucleoside 15 in 71%. Standard DMTr protection furnished compound 16 which was then activated for oligonucleotide solid-phase synthesis (SPS) by phosphitylation using CEP-Cl. The total yield of tCnitro deoxyribose phosphoramidite was 0.8% over 6 steps

• protection and phosphitylation using CEP-Cl generated the fully protected monomer ready for solid-phase synthesis [50]. The complete synthesis of the RNA building block of tCO was in this way achieved over five steps with a total yield of 28%, improved from the four step DNA building block synthesis of tCO

• glycosylation using Hoffer’s α-chloro sugar and compounds 52 and 53 provided the desired β-anomer after purification in 69% and 55% yield, respectively. Global deprotection using sodium methoxide followed by standard DMTr-protection and phosphitylation provides the activated monomers for solid-phase synthesis

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• solid-phase synthesis is limited in its maximum length, RNAs with a length of several thousand nucleotides can easily be prepared through IVT. On the other hand, enzymatically produced RNA is often inhomogeneous in length and for short RNAs the yields obtained after purification may be low. This impedes

• adenosyltransferase variant (MAT-Var.). The AdoMet analogue was directly converted by the methyltransferases, resulting in double alkyne modified cap analogues [95]. Chemical synthesis of capped mRNA Solid-phase synthesis of capped RNA Chemical synthesis of capped RNA is based on the solid-phase synthesis of RNA

• followed by chemical or enzymatic installation of the 5′-cap. The general principle of solid-phase RNA synthesis is beyond the scope of this review and has been described in excellent review articles [101][102][103][104]. The longest RNA synthesized via solid-phase chemistry to date has a length of 170

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• alkene analogues (Table 4). Comparison between Phe-ψ[(Z)-CF=CH]-Gly and Phe-ψ[(E)-CF=CH]-Gly isosteres and their alkene analogues was also performed in an antagonist activity study towards GPR54. The fluorinated isosteres were incorporated into pentapeptides using Fmoc solid phase peptide synthesis (SPPS

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• observed by 1H NMR spectroscopy [8]. Similar systems were prepared on solid phase and used as a new molecular recognition system [44]. The [4 + 2]-cycloaddition reactions of E- and Z-1b with electron-rich 1,3-dienes have been studied extensively by Sustmann and collaborators. Thus, 1-methoxybuta-1,3-diene

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• ][58]. This supramolecular behavior was also involved in the development of organic materials exhibiting proton conduction [59], or organo-gel properties [60]. In the field of analytical chemistry, molecules functionalized with phosphonic acid groups were used to prepare the solid phase for immobilized

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• ][13][14], fluorine-supported glycosylation [15][16] and automated solid-phase synthesis [17]. All of these methods use the donor/acceptor premixed approach and preferential activation of the donor is achieved by the higher anomeric reactivity of the donor towards the promoter compared to the acceptor

• hexasaccharide 105 was prepared within 7 hours in an excellent overall yield of 47% from the sequential one-pot reaction of 101, 102, 103 and 104. Compared to the automated solid-phase synthesis of Globo-H [61], the solution-based preactivation-based synthesis gave a higher overall yield for glyco-assembly (47

• to selectively “catch” the desired tetrasaccharide 153, which was rapidly separated from non-fluorinated impurities by fluorous solid-phase extraction (F-SPE). Subsequent release of the compound from the fluorous tag and F-SPE yielded pure 153 in 61% overall yield from donor 83. One potential side

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• Abstract While presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, the challenging VVIA tetrapeptide was

• research laboratories and for industrial production: synthesis in solution and synthesis on a solid support (also known as solid-phase peptide synthesis, SPPS). Indeed, liquid reaction mixtures enable efficient agitation when using a conventional batch reactor equipped with either magnetic stirring bar or

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• synthesis and purification by using well developed peptide coupling reactions with or without the use of solid phase methods. To execute this concept, Fairbanks et al. investigated a number of peptide chains with various amino acids as templates (Scheme 9) [76][77]. Using DCC-mediated coupling reactions

Spatial effects in polymer chemistry

• Helmut Ritter

Beilstein J. Org. Chem. 2017, 13, 2015–2016, doi:10.3762/bjoc.13.198

• the solid phase is not only influenced by external forces, for example, during extrusion, but is often also a result of chain mobility and strong intermolecular interactions. It should also be mentioned that the solubility of polymer chains is a spatial interplay between the solvent molecules and the

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) were employed as co-promoters in solution or automated glycan assembly on solid phase. Keywords: automated glycan assembly; 1,3-dibromo-5,5-dimethylhydantoin; glycosylation; promoter; thioglycosides; Introduction Thioglycosides are versatile glycosylating

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted. Keywords: ball-milling; green chemistry; mechanochemistry; solid-phase synthesis; solvent-free synthesis

• Hantzsch pyrrole synthesis is well known for the construction of poly substituted pyrroles [121][122]. In 1998, Jung and co-workers reported polymer supported solid phase synthesis of N-substituted pyrroles [123]. In 2013, Menendez and co-workers reported a ceric ammonium nitrate (CAN) and silver-nitrate

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• chain [12]. In order to reduce the number of linear steps, the protected guanidino group was included in the side chain building block in our case. This strategy would allow to assemble the complete peptide core in a solid-phase synthesis and to perform the solution-phase coupling without a large excess

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• has been regarded as an approach that could combine the advantageous features of both the solution and solid-phase syntheses. The critical step of this approach is the separation of the support-anchored oligonucleotide chain from the monomeric building block and other small molecular reagents and

• supports. While major advances in the large scale solid-phase technology have been taken, the difference in the consumption of building blocks in solution and on a solid-support is not necessarily as substantial as previously assumed; the phosphoramidite-chemistry-based synthesis has been optimized to the

• , chromatography, extraction and nanofiltration have been considered to be feasible approaches. Even if the synthesis on a soluble support fails to compete with industrial solid-phase synthesis, it may still play an important role in up to gram scale laboratory synthesis, since no special equipment is usually

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• monoprotected 1,2-cis galactopyranosides in good yield [42]. The conditions were also shown to be feasible for solid-phase synthesis. By employing BF3·DMF, the 1,2-cis-monoprotected galactopyranosides were obtained in excellent yield and good diastereoselectively in a short time (usually 30 min). The conditions

• furanosides. These may find application as enzyme substrates and possibly as inhibitors in several bacterial diseases, as well as in solid-phase-oligosaccharide synthesis, as shown. However, the main drawback is still the multistep synthesis of these anomeric activating donors. 3.2 Self-activation of the

• using the same one-pot strategy [78]. In a follow up work by Novoa et al. [79] by using NEt3 and DMC, S-linked glycopeptides at cysteine residues on a solid phase could also be obtained. This methodology or very similar variations thereof is now being utilized by several laboratories for various

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• during the synthesis of various glycosyl linkages not only in solution phase but also in solid-phase oligosaccharide synthesis [6][7][8][9][11]. Glycosyl sulfones were also used as donors in the preparation of various C- and O- linked oligosaccharides and functionalized glycols [8][9][12]. In addition

• available, inexpensive and nontoxic. The application of UHP as oxidant is well explored in various solution- as well as solid-phase organic syntheses [25][26][27][28]. In fact, we have recently reported the oxidation of arylboronic acids into corresponding phenols by using UHP as a selective oxidizing agent

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• proved highly efficient in solid-phase synthesis of a somatostatin analogue bearing three Nα-methylation sites that could not be synthesized using the previously described state-of-the-art methods. Keywords: N-methylation; nucleophilic addition; solid phase; somatostatin; sulfonylation; Introduction

• Scanlan adjusted the o-NBS strategy to solid-phase synthesis and introduced a general three-step procedure for Nα-mono-methylation of amino acids on solid support that was based on the work of Fukuyama [17][22][23]. Kessler and co-workers presented a time saving and cost effective three-step N-methylation

• significant decrease in the amount of side products was observed (Table 1, entries 3 and 4). When a combination of the most optimal conditions until this point was used, the conversion of 1 to 1a reached only 86% (Table 1, entry 6). Collidine is a common reagent for solid-phase synthesis (SPS) reagent and is

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• HRMS (Scheme 7). Discussion Above we mentioned that an addition of MeLi or PhLi in ether to a solution of 1-K in DME caused immediate precipitation. The combination of 1-K in DME with BuLi in hexanes or PhC≡CLi in ether does not lead to the formation of a solid phase. Because etherial solutions of MeLi

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• ] cyclotrimerization of the dialkyne 306 with variously disubstituted alkynes 307 performed on a solid phase TentaGel® resin (0.25 mmol/g) in the presence of Ru catalyst (Scheme 86). In case of 309–316, this reaction led to the formation of mixtures of two regioisomers. The examined regioisomeric ratios (a/b) were

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• -guided introduction of an azide functionality into electrophilic natural products and the subsequent azide enrichment on a solid phase facilitates the detection of epoxides and α,β-unsaturated enones in XAD extracts of Photorhabdus. Epoxystilbene (1) and glidobactins have never been observed before in

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• , 76344 Eggenstein-Leopoldshafen, Germany 10.3762/bjoc.13.16 Abstract The arabino-configured analog of uridine with a propargyl group at the 2’-position was synthesized and incorporated into DNA by solid-phase chemistry. The fluorescence quantum yields of DNA strands that were postsynthetically modified

• cannot only be applied for conventional postsynthetic oligonucleotide modification in solution but also on solid phase [11] and for the introduction of multiple postsynthetic modifications [12]. The azide groups for CuAAC are typically placed onto the fluorescent dyes since azides are not compatible with

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• electron supply to the P450s (Figure 3) [38]. NADH was additionally regenerated throughout the assay via a glucose/glucose oxidase couple. The assay was stopped by cleaving the peptide from the PCP-X constructs using excess of methylamine and the peptide was then purified by solid phase extraction before

• electron source [38], and finally the peptides were purified by solid-phase extraction and analysed HPLC–MS [17]. The StaF activity assays with Tei7-L-Hpg7 as substrate were performed both with and without StaH. All other StaF activity assays were always performed together with StaH. StaF protein

• ring formation between D-Tyr2 and D-Hpg4. 3) The reaction is quenched by the addition of methylamine, which cleaves off the peptide from the phosphopantetheine linker thus liberating the peptide methylamide. 4) The peptide is purified by solid phase extraction (SPE) and 5) analysed by LC–MS in single