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

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• were used for combinatorial solid phase or automated spot synthesis of libraries of highly glycosylated peptides and shown to specifically bind to lectins [5][8][10]. Here, we now describe the preparation of a series of glycopeptide building blocks which allow for the construction of glycopeptide

• of the two gluco-dipeptides were only in the medium range due to traces of unidentified byproducts which could not easily removed during chromatographic purification. Nevertheless, the only medium yields in this case can be circumvented in solid phase syntheses of such glycopeptides where an excess

• of one building block can be applied and no chromatographic purification is necessary. Such combinatorial solid phase syntheses with the building blocks described here are now underway. Conclusion We have described the preparation of a series of new aromatic glycopeptoids and have demonstrated their

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• Supporting Information File 1). The di- and trivalent guest strands 8–14 (Figure 1C, D) were synthesized by solid phase peptide synthesis using a standard Fmoc-protocol (Figure 3). Therefore the serine derivatives 15 and 16 (Figure 1E) and a water-soluble linker molecule were used. The purity of the guest

• ). Synthesis of the di- and trivalent CD sequences 1–7 (for detailed reaction conditions see Supporting Information File 1). Solid phase peptide synthesis of the di- and trivalent guest strands 8 – 14 (for detailed reaction conditions see Supporting Information File 1). 1H NMR spectra of 17 (B) and its

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build

• . Synthesis Schemes 1–4 show the syntheses of the SAN conjugates formed by the reaction of the amino acid segment with the nucleobase and the saccharide derivative. The key steps include N-alkylation, acetylation, solid-phase peptide synthesis (SPPS) and N-hydroxysuccinimide (NHS)/N,N-diisopropylcarbodiimide

• 12, 16, and 19. Solid-phase peptide synthesis of peptide segment Fmoc-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-OH (20). Synthesis of H-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-adenine (22). Synthesis of saccharide–amino acids–nucleobase conjugate 3. Supporting Information Supporting Information File 432

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• long DNA (L-DNA) constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide “letters”, the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non

• systems; solid-phase DNA synthesis; synthetic biology; Introduction It has been nearly 50 years since the first solid-phase synthesis of DNA by Letsinger and Mahadevan [1][2]. This work laid the platform for new strategies in oligonucleotide synthesis, culminating in the development of phosphoramidite

• to assist in downstream processing. Thus, the complete target L-DNA sequence had 863 base pairs. Synthesis The oligonucleotides containing S and B shown in Table 1 were obtained from IDT, where they were prepared by automated solid phase phosphoramidite-based synthesis following the procedure of

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• extrahelical side and thus has an important contribution to the overall DNA-binding energy of M.TaqI. Experimental Solid-phase DNA synthesis was performed on an ABI DNA Synthesizer 392 in 1 µmol scale following the standard cycles recommended by Applied Biosystems with a coupling time of 30 s for the natural