Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• are seen with DNA analogs 22c and 24c, in full accord with NUPACK predictions and the experimentally observed levels of modulation depth. Conclusion All three phosphoramidite building blocks 5, 7, and 8 are applicable for automated solid-phase synthesis using standard reaction cycles. As in the case

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• phase synthetic approach for the syntheses of cyclic Py/Im polyamides [84]. This group previously optimized and reported a machine-assisted Fmoc solid phase synthesis of simpler polyamides to afford high step-wise coupling yield [85]. A seven-member library of cyclic polyamides targeting androgen

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

• 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

• this strategy the large scale synthesis (5 g) of 3'-unprotected trinucleotides proceeded with a total 75–90% yield [20]. Other strategies with potential for the solid-phase synthesis of protected trinucleotides might rely on a universal solid support, from which oligomers with free 3'-OH function are

• strategy and syntheses will be described elsewhere. 3. Preparation of trinucleotides by inverse solid-phase synthesis Interestingly, also the use of polymer-supported reagents for H-phosphonate or phosphoramidite activation and phosphite oxidation has been described [34][39], thereby combining the

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

• ]. 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

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

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

• , 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

• phosphitylation with 1-chloro-1-(2-cyanoethoxy)-N,N-diisopropylphosphoramidite gave the desired building blocks, the applicability of which in a solid-phase synthesis was demonstrated [45]. 3´-(2-Chlorophenyl)phosphates of protected trimeric ODNs, useful for phosphotriester coupling, have been prepared on a

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

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

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

• -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

• studied in view of stereoselectivity at all. The regiocontrol of hetero-Diels–Alder reactions requires additional research for both, solution as well as solid-phase synthesis. The regiocontrol in solution involving arylnitroso derivatives has been poorly explored, while the use of catalysts with

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

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

• polyamides is a direct solid-phase synthesis using terminal azide or alkyne-containing carboxyl synthons as the last step of the MGB’s synthesis (see reference [2]). Synthesis and fluorescent properties of fluorescent probes based on polyamides For fluorescent labeling of polyamides we used a polyamide F1

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

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

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

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

• 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

• density. Synthesis of glycoconjugate DNA by diazo-coupling. β-Galactose-modified deoxyuridine phosphoramidite used for solid-phase DNA synthesis and DNA display of glycan. (NHS)-carboxy-dT phosphoramidite as a general entry for the solid-phase synthesis of glycan–DNA conjugates. Preparation of the DNA

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

• -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

• 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

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