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

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• 13 to deliver (S)-homolaudanosine, a natural product from an alkaloid family with neurologic activity, in high yield and enantiopurity. They also demonstrated that this alkynylation is amenable to solid phase synthesis; alkyne 14 was prepared by alkynylation of an isoquinolinium ion linked to a

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• , Aβ peptide pentapeptide boronic acids 1 and 2 were synthesized by solid-phase peptide synthesis and studied in esterification experiments with polyhydroxylated templates. The bis-hydroxylated dipeptide Hot=Tap serves as a template of adjustable degree of oligomerization which spontaneously forms

• obtained by routine solid-phase peptide synthesis on chloro-(2'-chloro)trityl polystyrene (CTC resin) and coupling of the unprotected boronic acid as the final building block. The C-terminal boronic acids need careful exclusion of water because of the reversible linkage to the resin, while no special

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• activity was shown for tyrosine and both threonine building blocks, marked by asterisks in Figure 4. Moreover, one leucine could be determined as D-configured according to incorporation in truncated fragments of 16. For the elucidation of the second stereocenter in both threonines, solid phase synthesis of

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• ) were added to a mixture of sulfide 1a and 3HF·Et3N (3.0 equivalents) at 0 ºC, but no reactions took place under these conditions. The HBF4·SiO2 reagent was chosen as a solid phase-supported HBF4 equivalent [14]; carrying out the reaction in the presence of this reactant and 3HF·Et3N led to complete

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• quencher are disconnected resulting in the fluorescent product 7. A similar linker concept has previously been implemented for a solid-phase linker in the synthesis of oligosaccharides [18][19]. The second profluorescent molecule selected was diolefin 8, which yields fluorescent 7-hydroxycoumarin

Polythiophene and oligothiophene systems modified by TTF electroactive units for organic electronics

• Alexander L. Kanibolotsky,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1749–1766, doi:10.3762/bjoc.11.191

• activity and to further increase the dimensionality of their intermolecular interactions in the solid phase, the TTF units were incorporated into dendritic structures [28][29][30][31][32]. The extraordinary propensity of TTF and its doped species to aggregate was the reason for using this unit in the

• from those in solution (−4.95/−3.55 eV), which suggested significant donor–acceptor interactions in the solid phase between the DPP and TTF units. OFET device fabrication employing polymer 48 exhibited p-type semiconductor behaviour, with the best performance from devices using the bottom contact top

• dithienyl-thieno-TTF unit and the localised nature of the LUMO led to donor–acceptor interactions in the solid phase, making it impossible for efficient overlap between LUMOs, which would normally be required for an efficient n-type semiconductor. BHJSCs were fabricated from 48 as the electron donor and

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• substituted indoles 1–4. Using a solid-phase screen as before, the level of colour formation in colonies was assessed visually, generating ‘fingerprints’ of activity as summarised in Figure 2 (also see Figure S1, Supporting Information File 1). The fingerprints show that variations in the configuration of the

• (R,S)-12 alcohols (37%) albeit with a slight decrease in selectivity (15%). Conclusion A colony-based solid-phase screen for P450 indole activity was developed and used to generate a population of 93 indole active enzyme variants from screening a large library (16,500) of variants. The application of

• ), Met184/Thr185 III (red), Leu244/Val247 IV (cyan), Gly248/Thr252 V (magenta), Val295/Asp297 VI (blue), Ile395/Val396 VII (orange). Following pairwise mutagenesis and solid-phase screening (using indole (1) as substrate), 93 new indigo positive variants were identified as represented in the grid. The grid

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• that govern the interaction of nucleic acids with small molecular entities and other biopolymers has increased. In particular, for NMR spectroscopic studies of such interactions, oligonucleotides are often required in quantities that are inconvenient to prepare by laboratory scale solid-phase synthesis

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• .11.145 Abstract This article reports the synthesis of a new class of conjugates containing a nucleobase, a peptidic epitope, and a saccharide and the evalution of their gelation, biostability, and cell compatibility. We demonstrate a facile synthetic process, based on solid-phase peptide synthesis of

• designed the nucleopeptides 5 and 6. In addition, we substituted thymine with adenine to generate nucleopeptides 7 and 8 that contain adenine, the nucleobase is complementary of thymine. Synthesis The NA conjugates 5–8 were obtained according to a facile method of solid-phase peptide synthesis (SPPS) [17

• solid-phase peptide synthesis and liquid-phase synthesis). i) Fmoc-Val-OH, DIPEA; ii) 20% piperidine; iii) Fmoc-Pro-OH, HBTU, DIPEA; iv) Fmoc-Thr(t-Bu)-OH, HBTU, DIPEA; v) thymine-1-acetic acid, HBTU, DIPEA; vi) TFE/DCM 2:8; vii) D-glucosamine hydrochloride, HBTU, DIPEA; viii) TFA/H2O 95:5

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• its capacity to run as an uninterrupted process is certainly limited by the solid-phase scavengers employed as purification aids. The stoichiometric scavenging capacity of many of these species coupled with their limited loadings does restrict the quantities of material which can be generated in a run

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• alkyne by oxidative amidation using carbon tetrachloride with propargylamine. The microwave-assisted click-conjugation was performed on a solid phase upon completion of the DNA synthesis (Scheme 4). Lönnberg and co-workers prepared a thymidine modified at the 4’-position with an azidomethyl group to

• achieve conjugation during solid-phase DNA synthesis or in solution post DNA cleavage [28]. Subsequently, the same group reported a method to introduce two different glycans sequentially on the DNA strand at the 2’-position using an azido and a bromo-modified thymidine 6 and 7 (Scheme 5) [29]. Krauss and

• solid-phase synthesis have enabled the introduction of complex glycans with modest synthetic investments to obtain the suitably functionalized glycans. Furthermore, methods to access large libraries of peptidoglycan conjugates with nucleic acid tags have been reported opening new horizons in the

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• 10.3762/bjoc.11.69 Abstract A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively. Keywords: α-sialylation; automated synthesis; glycosylation; sialic acid; solid

• did not result in a satisfactory yield and demonstrates a current limitation of the automated glycan assembly approach. Recently, placement of an isothiocyanate moiety on the C5 position was reported to be an effective method to construct alpha linkages [22] and may prove useful for solid-phase

• -phase synthesis; Introduction N-Acetylneuraminic acid (sialic acid, Neu5Ac) is an important component of mammalian glycans and key to many recognition events of biomedical relevance including cell–cell recognition, signaling, and the immune response [1]. Sialic acids are present in tumor-associated

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• UC-containing oligonucleotides The phosphoramidites of TA (5), UA (10) and UC (14) were used to incorporate the spin-labeled nucleosides into DNA oligonucleotides using solid-phase synthesis [77]. The low stability of the nitroxide functional group in the TEMPO moiety towards acids lead to almost ca

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• coupling to give the dinucleoside acylphosphonites proceeded smoothly, but separation of the pure compounds from the nucleoside precursors could not be completely achieved. If the pure acylphosphonites are to be obtained, solid-phase synthesis would probably be required. The chromatography results

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step

• physiological pH values, thus leading to a (partially) zwitterionic backbone structure in NAA-modified oligonucleotides. We have previously described that NAA-modified DNA oligonucleotides can be obtained by standard solid phase-supported automated DNA synthesis, using the 'dimeric' phosphoramidite building

• (S)-7 and (R)-7 were then employed for solid phase-supported automated DNA synthesis, which afforded novel zwitterionic oligonucleotides 31 and 32 bearing the NAA-modification at A–T sites. Overall, it was therefore demonstrated that the synthesis of different 'dimeric' NAA-linked X–T

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• of a new crystalline phase (curve (c)). The same endothermic peak was present in the KN (curve (d) (and MW, curve not shown) products, preceded by a small exothermic effect at 120 °C, confirming the TMA–RSV interaction and formation of a new thermally-induced solid phase. Comparison of FTIR spectra

• complexation. It should be noted that, in general, solid-state characterization using the latter techniques is limited, the evidence for genuine inclusion complex formation not always being definitive because the preparative method may result in one or both components becoming amorphous, or an unexpected solid

• phase (e.g., a hydrate of the guest compound) might be generated during attempted complexation. Loss of crystallinity of CD inclusion compounds also results when they dehydrate, rendering their PXRD traces less informative. There is, hitherto, a distinct lack of information on the structural nature of

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• aim to facilitate structural modifications in DNA and RNA targeting by oligo-aryl derivatives, new amino acids with phenanthridine attached to the side chain were prepared and the solid phase synthesis of novel peptide-bridged bis-phenanthridine derivatives was developed (Figure 4) [68], whereby the

• structural explanation of observed ICD recognition. Laborious synthetic procedures for the preparation of bis-phenanthridine–nucleobase conjugates initiated a novel, convergent and much more flexible approach relying on solid phase peptide synthesis described earlier (Figure 4). In such a manner prepared

Nucleic acid chemistry

• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2014, 10, 2928–2929, doi:10.3762/bjoc.10.311

• phosphordiesters or -triesters. Finally, this approach using phosphoramidites as nucleoside building blocks was significantly further developed in 1981 by Beaucage and Caruthers [4]. Since then, oligonucleotides of up to 50-mers in length have become available by an extremely efficient solid-phase methodology that

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• test on residual amino groups of amino acids in solid-phase supported peptide synthesis. A report on a quantitative variation of the Kaiser test was published by Sarin et al. [23]. As this assay is colorimetric, its execution is very convenient. One limitation of the method, though, is the restriction

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• enabled by techniques such as solid phase synthesis, post synthetic modifications or enzymatic incorporation of modified analogues. Originating from research into aptamers as strong and selective binders [12][13][14], several research groups are investigating the creation and synthesis of new DNA or RNA

• have a stable and predictable structure allowing the design of engineered active sites through the carefully planned introduction of extra catalytic functionalities via solid phase DNA synthesis. We have further recently shown that the combination of solid phase synthesis and molecular modeling

• functionalized amino acids onto nucleoside building blocks (Figure 1). Following the event of solid phase peptide synthesis, a large range of amino acids with different protection schemes and stereochemistry is currently commercially available. We here illustrate a methodology for direct incorporation of amino