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

• . Similarly, in the search for thiophosphate protecting groups with deprotection half-lives in the range of 100–200 h at 37 °C for sustained CpG ODN immunostimulation in animal models, Beaucage et al. have developed a new class of thermosensitive groups that are hydroxy-alkylated phosphoramidate

• ) phosphoramidothioylbutyl groups to TpsT proceeded with respective half-lives of 135 h, 245 h and 265 h at 37 °C. Therefore, these groups are appropriate for thiophosphate protection of the CpG motif of CpG ODN prodrugs, and they are complementary to those identified earlier [60]. It remains to study such thermosensitive

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• reacted in situ, because it rapidly dimerizes or polymerizes in solvents of medium polarity such as chloroform (t1/2 = 2 h). We observed longer half-lives in low polarity solvents (t1/2 = 12 h in toluene-d8, 150 mM, 27 °C). We have been able to purify the compound by chromatography and to isolate it as a

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• mammalian mannose-binding sites are in general flat and solvent exposed, the half-lives of carbohydrate–lectin complexes are rather short since water molecules can easily access and displace the ligand from the binding site. In contrast, the bacterial lectin FimH benefits from a deep mannose-binding site

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• ], leading to significant improvements in blood circulation half-lives, decrease in clearance rates, and prolonged pharmacological effects [12][13][14]. Derivatives of PEG are often used to perform conjugation reactions on small molecule drugs, proteins, or bioactive nanomaterials [15]. Other methods include

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• half-lives. The experimental results are supported by DFT calculations, and we provide a possible explanation for the reduced thermal stability of ethyl halodiazoacetates compared to ethyl diazoacetate and for the relative decomposition rates between the chloro, bromo and iodo analogs. We have also

• briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II)-catalyzed reactions. Keywords: carbenes; catalysis; cyclopropanation; halo diazoacetates; half-lives; thermal stability; Introduction The chemistry of diazo compounds has fascinated

• which implies first order kinetics. All the kinetic measurements made in this study followed the same first order kinetic profile [15] and the data obtained from the kinetic profiles are summarized in Table 1. As a point of reference, the half-lives (t1/2) for the non-stabilized diazo compounds 2

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• –S24). The appearance of a resonance at δ = 9.68 ppm is assigned to a trace amount of W(CO)5(Z-2). A dark precipitate (possibly tungsten nanoparticles [81][82]) forms during the thermolysis. The half-lives at 60, 70, 80, 90 and 100 °C amount to 145.9, 39.4, 28.9, 16.2 and 12.2 h. The time traces fit to

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• PNA. Previous results for the corresponding DNA conjugates had shown sequence specific RNA cleavage with substrate half-lives in the range of 12 to 17 h [16]. Tris(2-aminobenzimidazole) 7 can be obtained in a six-step reaction sequence starting from tris(2-aminoethyl)amine (1) [15]. However, the use

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• adenovirus coat for vaccine development [5], antibodies or antibody fragments to prolong their circulating half-lives in vivo [6] and selective alkylation and acylation of amino groups in a somatostatin analog using two different PEG reagents [7]. Also, PEGylation of low molecular weight drugs in order to

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• derivatives [12]. Besides this success story, there are limitations restricting the use of peptides as drugs (Table 1). Notably, their low bioavailability owing to proteolytic degradation by enzymes of the intestine, blood and cell plasma leads to short circulating half-lives [13]. Depending on their size

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• isothiocyanophosphate was reacted with excess aniline for more than 15 half-lives at 55.0 °C in MeCN. Acetonitrile was evaporated under reduced pressure. The product mixture was treated with ether by a work-up process with dilute HCl and dried over anhydrous MgSO4. The product was isolated through column chromatography

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• unbleached. Chemical probes also have a variety of half-lives in vivo, a property that may be beneficial in some assays compared to long-lived fluorescent markers, such as mitoGFP and related proteins. High-content screening of chemical libraries against C. elegans treated with HRB 9 and HR101 10 may

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• been described as a method to improve the solubility of drugs, prolong their half-lives in plasma, or modulate their pharmacokinetics [35]. An effect not described to our knowledge so far is that pegylation can enhance, several hundred-fold, the penetration of a hydrophilic drug into cells. Linkers

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• cyclodextrin derivatives were used in excess with respect to GF. Similar trends were observed for the other cyclodextrin derivatives, although their overall rates of conversion were consistently lower than those of 1b. Quantitative information in terms of the observed rate constants kobs and half-lives t1/2was

Intramolecular hydroxycarbene C–H-insertion: The curious case of (o-methoxyphenyl)hydroxycarbene

• Dennis Gerbig,
• David Ley,
• Hans Peter Reisenauer and
• Peter R. Schreiner

Beilstein J. Org. Chem. 2010, 6, 1061–1069, doi:10.3762/bjoc.6.121

• , only the substituted anisaldehyde 11 could be identified. On repeating the experiment with deuterated acid (OD) d-10, no deutero-carbene d-12 was likewise produced, as verified by subsequent irradiation (577 nm, 313 nm). The computed [1,2]H-tunneling half-lives of 5 and 12, based on a) an Eckart

• barrier approach, and b) the Wentzel–Kramers–Brillouin (WKB) approximation (see Computational methods for details), are summarized in Table 1, together with the computed half-life of 3 for comparison. Based on the computed tunneling half-lives, 12 should be observable in matrix-isolation experiments if it

• performed, containing radii based on the United Atom Topological Model as implemented in Gaussian09. Tunneling half-lives τ1/2 of carbenes 5 and 12 were estimated employing a) a simple Eckart barrier methodology [36][37], and b) the one-dimensional Wentzel–Kramers–Brillouin approximation [13][14][37][38

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• mimics of biologically important α-peptides [54] and this holds great therapeutic promise because β-peptides are not recognised by hydrolase enzymes so have much longer half-lives in vivo [55]. One way to control the conformation of β-peptides is to incorporate fluorine atoms into the peptide backbone