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

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• peptomers by Ostergaard and Holm [45]) prodrugs that can be selectively activated by prostate cancer cells. Peptidomimetics can be conveniently synthesized using the so called "submonomer approach" either in solution [41] or in solid-phase [46][47]. However, some disadvantages have been reported for long or

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

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• fusion proteins were subjected to the ATP-[32P]pyrophosphate exchange assay. In this assay, the protein is incubated with a potential substrate, ATP and radioactive pyrophosphate. The reversible back exchange of [32P]pyrophosphate into ATP is quantified by scintillation counting after solid phase capture

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• Elisabeth Mairhofer Elisabeth Fuchs Ronald Micura Institute of Organic Chemistry and Center for Molecular Biosciences, University of Innsbruck, Austria 10.3762/bjoc.12.250 Abstract Access to 3-deazaadenosine (c3A) building blocks for RNA solid-phase synthesis represents a severe bottleneck in

• building blocks for RNA solid-phase synthesis represents a severe bottleneck in modern RNA research, in particular for studies that aim at the mechanistic elucidation of site-specific backbone cleavage of recently discovered ribozyme classes, known as twister, twister sister, pistol, and hatchet RNA

• ], started from inosine leading to c3A after 8 steps via a 5-amino-4-imidazolecarboxamide (AICA) riboside derivative with 8% overall yield. Another 4 steps followed to achieve a properly protected building block for RNA solid-phase synthesis [16]. With a total of 12 steps, the approach is not very attractive

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• et al. [47]. These syntheses substituted the enduracididine residue for the more readily available L-arginine. The total synthesis of the full teixobactin structure was completed in 2016 by Payne et al. [72] using Fmoc solid-phase peptide synthesis (SPPS). The key to the synthesis was access to the

• synthetic routes to enduracididine. However, current syntheses are cumbersome and inefficient. A robust and scalable synthetic route to an orthogonally protected enduracididine derivative suitable for solid phase peptide synthesis would greatly facilitate antibiotic drug development focused on a teixobactin

• -hydroxyenduracididine 98. Total synthesis of mannopeptimycin α (12) and β (13). Synthesis of protected L-allo-enduracididine 102. The solid phase synthesis of teixobactin (17). Retrosynthesis of the macrocyclic core 109 of teixobactin (17). Synthesis of macrocycle 117. Acknowledgements The authors would like to thank

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

• libraries of reversibly interconverting building blocks. The syntheses of phosphoramidite building blocks derived from D-threoninol are presented in two variants with protected amino or thiol groups. The threoninol building blocks were successfully incorporated via automated solid-phase synthesis into 13mer

• analogue. Keywords: base-pairing; base-pair mismatch; DNA functionalization; DNA templates; dynamic combinatorial chemistry; D-threoninol based scaffolds; Introduction The well-defined duplex structure, self-assembling by base-pair recognition, and the accessibility by solid-phase synthesis make DNA

• , incorporated into oligonucleotides by standard solid–phase synthesis and reacted with the desired molecules on the oligonucleotide level. As amines and thiols are among the widely used groups introduced for the post-synthetic modifications, the acyclic threoninol linker (2-amino-1,3-butanediol) [14][15][16][17

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• transformation, hydrogen peroxide and m-CPBA are the most popular (see examples in Scheme 4). In the literature, the oxidation of hydroxylamines is described most frequently using Fe(III) salts, m-CPBA or TBAPI and the reaction is performed exclusively using a solid-phase synthetic approach (see examples in

• (CH2Cl2 or toluene) and at different temperatures (−20 °C or rt), gave the hetero-Diels–Alder products 70,71, with the ratio of 70 and 71 varying from 71:29–83:17, and yields between 65 and 99%. Comparison of the regioselectivity in solution and solid-phase nitroso hetero-Diels–Alder reactions

• Experimentally, the general rules of regioselectivity mentioned above hold true in most cases for both solution and solid-phase hetero-Diels–Alder reactions. The regioselectivity of the nitroso hetero-Diels–Alder reaction in solution has been studied in detail, e.g., [79][80][87][97], and the general rules for

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• ], multiphasic reactions including solid-phase protocols [18], addition of gaseous reagents [19], high-pressure conditions [20], cascade conversions without intermediate work-up operations [21], as well as thin film, falling film [22], micro-channel [23], and tube-in-tube reactors [24][25] for reactions between

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

• ; oligosaccharides; solid-phase synthesis; Streptococcus pneumoniae; Introduction The Gram-positive encapsulated commensal bacterium Streptococcus pneumoniae [1][2][3] can cause serious medical conditions like pneumonia, meningitis, endocarditis and sepsis [4]. S. pneumoniae is the leading cause of vaccine

• and solid support for the automated solid-phase synthesis of S. pneumoniae serotype 3 CPS structures. HPLC chromatogram of the crude products of the attempted AGA of SP3 trisaccharide 5; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 55% EtOAc (70 min), ELSD. HPLC chromatogram of the crude

• products of the attempted AGA of SP3 trisaccharide 9; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 70% EtOAc (70 min), ELSD. HPLC chromatogram of the crude products of the automated solid-phase SP3 trisaccharide 5 synthesis; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 60% EtOAc (60 min

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• . demonstrated the fluorescent labeling of proteins directly in living cells by copper-free "click chemistry" [29]. Alkyne or azide groups can be inserted into both TFO and MGB using enzymatic or chemical methods during matrix or solid-phase synthesis [2][30][31] or post-synthetically using described conjugation

• of oligonucleotides) or an activated carboxylic ester for reactions with nucleophiles (for example, terminal amino groups of MGBs). The linkers have various lengths and chemical natures and can be coupled either directly during a solid-phase synthesis or post-synthetically to pre-synthesized or

• -aminobutyric acid, Py – N-methylpyrrole carboxamide and Dp – N,N-dimethylaminopropylamine residues) was synthesized in the laboratory by solid-phase method [36][37] and used as a polyamide component. The first model is interesting for an anti-HIV strategy, but it is not suitable for visualization of dsDNA