Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• their high thermal stability, low toxicity to human cells and effective broad-spectrum antibacterial activity. The antibacterial activity of these nanoparticles is probably due to their rapid breakdown which releases ionic silver that interact with the thiol residues of bacterial enzymes [80]. As a

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

• the addition of thiol reagents like dithiothreitol. This property makes the cross-linking reaction fully reversible and allows for a switching of the linked base pair from locked to unlocked during biochemical experiments. Using the DNA methyltransferase from Thermus aquaticus (M.TaqI) as example, we

• thiol groups, which, upon removal of reducing agent, react under oxidative conditions to form a disulfide cross-link. Adjacent A/A, C/C, G/G and T/T cross-links have been synthesized with this method. An interstrand G/G cross-link of adjacent G/C base pairs was used to study binding of the DNA cytosine

• obtained by choosing the corresponding I6S/U4S or G6S/U4S thionucleobase pair. The cross-linked duplexes can be isolated and were stable in the absence of reducing agent. Traceless linker removal with thiol nucleophiles The covalent ethylene cross-links in 1I6S-Et-S4U2 and 1G6S-Et-S4U2 are stable at room

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• Vivadent AG, Bendererstrasse 2, 9494 Schaan, Principality of Liechtenstein Heraeus Kulzer GmbH, Philipp-Reis-Straße 8, 61273 Wehrheim, Germany 10.3762/bjoc.10.180 Abstract Thiol–ene photopolymerizations gain a growing interest in academic research. Coatings and dental restoratives are interesting

• applications for thiol–ene photopolymerizations due to their unique features. In most studies the relative flexible and hydrophilic ester derivative, namely pentaerythritoltetra(3-mercaptopropionate) (PETMP), is investigated as the thiol component. Thus, in the present study we are encouraged to investigate

• the performance of more hydrophobic ester-free thiol-modified bis- and trisphenol derivatives in thiol–ene photopolymerizations. For this, six different thiol-modified bis- and trisphenol derivatives exhibiting four to six thiol groups are synthesized via the radical addition of thioacetic acid to

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• heterobifunctional dendrons were designed in order to have bio-orthogonal functional groups at the focal point and at their termini. More specifically, a double bond was placed at the desired matrix as the focal point for further conjugation by thiol–ene chemistry, and carbonyl groups were added at the termini. The

• dendrons in quantitative yields. The glycosylated dendrons can be exploited for further chemoselctive thiol–ene reactions with matrices suitably functionalized with thiol groups, i.e., cysteine residues in proteins. Experimental General methods All chemicals were purchased from Sigma-Aldrich and used

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• , and to deepen the understanding of how molecular structure influences the characteristics of self-assembly. Previous amphiphile libraries have been prepared using a thiol–yne reaction [14] and an in situ hydrazone formation between aldehyde tails and hydrazide head groups [15] in order to study gene

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• Abstract We describe the first one-pot orthogonal strategy to prepare well-defined cyclopeptide-based heteroglycoclusters (hGCs) from glycosyl thiols. Both thiol–chloroactetyl coupling (TCC) and thiol–ene coupling (TEC) have been used to decorate cyclopeptides regioselectively with diverse combination of

• successive attachment of sugar residues on a core scaffold such as sugar [6][7], peptide [8][9][10], dendrimer [11][12], cyclodextrin [13][14][15] and polymer [16]. The most common synthetic strategy to build such hGCs relies on a fragment-coupling approach using thiol–ene coupling [17], copper(I)-catalyzed

• ]. Herein we report a new strategy based on both thiol–chloroactetyl coupling (TCC) and thiol–ene coupling (TEC) to prepare hGCs from glycosyl thiols and cyclopeptide scaffolds displaying chloroacetyl (ClAc) and allyloxycarbonyl (Alloc) groups and vice versa. We demonstrate that cyclopeptides

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• etherification, thiol-ene reaction and in particular olefin cross metathesis. Keywords: amphiphilic glycomimetics; cross metathesis; glycodendrons; multivalent glycoconjugates; multivalent glycosystems; Introduction In addition to nucleic acids and proteins, molecular life is based on a third important class

• expected in case of the glycodendrons 3–9. However, the so-called “thiol-ene” reaction [10] gave reliable results with both bivalent and tetravalent glycodendrons. The radical addition of mercaptododecane to either 3 or 7, employing AIBN as radical starter, led to the amphiphilic thioethers 12 and 13

• ). Conclusion In conclusion, it was shown that readily available polyether glycodendrons can be refined employing suitable postsynthetic modification of the focal point. We have illustrated, that alkylation, thiol-ene reaction and in particular olefin cross metathesis leads to di- and tetravalent glycolipid

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

• ]. Several methods have been developed for site-directed PEGylation. One of the most popular involves the reaction of the thiol group in one or two cysteine residues with appropriate PEG derivatives. The cysteine could be originally present in the protein or introduced by mutagenesis [27][28]. The C-terminus

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs

• thioacetate [31], was reacted with ABC and 3TC in DMF in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) to obtain the ester derivative in ~75% yield. After purification, the protecting group of the thiol was removed with hydrazine acetate to give the

• corresponding ester prodrug candidates with a free thiol-ending group fundamental for their gold chemo-adsorption (Figure 1 and Supporting Information File 1). Abacavir (ABC) and lamivudine (3TC) were functionalized at the primary hydroxy groups through an ester bond that will be cleaved by cellular esterase

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• phosphorazidate (DPPA) and diethyl phosphorocyanidate (DEPC) are widely employed as peptide coupling reagents [59][60][61][62]. DPPA was also used in many organic reactions such as the Curtius rearrangement [59], the thiol ester synthesis [63], the azidation of alcohol and phenol [64], and the synthesis of

• . However, as reported in Scheme 32-ii, some chiral phosphoramidates and thiophosphoramidates can be readily synthesized with the AT reaction in high yield (85–88%) from dimethyl phosphite or O,O-dimethyl thiophosphite [106]. When the chiral amine was functionalized with a thiol group (Scheme 32-iii), the

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• ) synthesis. Probably, the same S–S-containing linker could be used in the synthesis of MorGly oligomers, but it should be examined. In our work we propose another approach, which has fewer steps and does not require the additional thiol treatment to cleave the oligomer from the support. In our previous work

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• synthesis of thermo-, oxidation- and cyclodextrin- (CD) responsive end-group-functionalized polymers, based on N,N-diethylacrylamide (DEAAm). In a classical free-radical chain transfer polymerization, using thiol-functionalized 4-alkylphenols, namely 3-(4-(1,1-dimethylethan-1-yl)phenoxy)propane-1-thiol and

• 3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propane-1-thiol, poly(N,N-diethylacrylamide) (PDEAAm) with well-defined hydrophobic end-groups is obtained. These end-group-functionalized polymers show different cloud point values, depending on the degree of polymerization and the presence of randomly

• agents [23][24][25] or (b) indirect by polymer analogous modification of existing end-groups. For the post-modification highly efficient reactions are needed to ensure a high degree of functionalization. For this reason, often “click reactions” [26] such as esterifications [27], azide–alkyne [22], thiol

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• :1 mixture of both 2,3-anti diastereomers 17a and 17b in 57% yield over two steps [22]. Such thiophenol esters readily undergo thiol-exchange reactions and are therefore suitable precursors for SNAc, pantetheine and CoA thioesters [14]. Accordingly, when we treated the mixture of thiophenol esters

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3. Keywords: ansamitocins; antibiotics

• ] were one of the earliest examples of folate disulfide–drug conjugates and after the conjugate is internalized by endocytosis, it was demonstrated that the endosomes exert reductive cleavage. For conjugate 7 we found that disulfide cleavage provided a thiol derivative of ansamitocin P-3 (4, AP-3) 8 with

• order to broaden the opportunities of this approach for the ansamitocins, we now describe alternative accesses towards disulfide linked conjugates that are based on thiol-functionalized AP-3 derivatives. These are planned to be obtained by a combined muta- and semisynthetic strategy using different

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• proceeds through a formation of an enol-containing complex with a metal ion (Scheme 57, Table 14). 3.3. Oxidation of 1,5-dienes in the presence of thiols The co-oxidation of 1,4-dienes and thiols (thiol–olefin co-oxygenation, TOCO reaction) was described for the first time by Beckwith and Wagner as a

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

• Samir Kundu,
• Babli Roy and
• Basudeb Basu

Beilstein J. Org. Chem. 2014, 10, 26–33, doi:10.3762/bjoc.10.5

• allyl bromide with excess thiol at room temperature is described. The choice of silica gel, either pre-calcined or moistened with water, exhibited notable regioselectivity in the formation of dithioethers. Plausible mechanistic routes were explored and postulated. Keywords: allyl halide; dithioether

• ; silica gel; tandem reactions; thiol; Introduction Organosulfur compounds are important building blocks for the synthesis of various biologically active molecules [1][2][3]. Versatile applications of organosulfur compounds are known in fields such as the pharmaceutical, the polymer, the pesticide and the

• showed varying results under conditions A or B, and allyl acetate did not undergo any desired reaction, but merely produced the disulfide from oxidative dimerization of the thiol (Table 1, entries 6–8). Allyl tosylate, however, produced the desired thioethers in a regioselective manner, but with

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides. Keywords: continuous flow; flow chemistry: flow synthesis; glycoligands; multivalency; photochemistry; solid-phase synthesis; thiol–ene; thioglycosides; Introduction Multivalent carbohydrate ligand

• [20]. Carbohydrate conjugation was achieved by copper-catalyzed azide alkyne cycloaddtion (CuAAC) of carbohydrate ligands on alkyne presenting oligomers [21]. As an alternative conjugation approach to CuAAc, a very efficient thiol–ene coupling (TEC) [22][23][24][25] protocol in a continuous flow

• removal of the desired product minimizes unwanted secondary reaction pathways [27][28][29][30][31][32][33][34][35][36][37][38][39]. We also introduced the so-called building block approach in the context of thiol–ene coupling via the continuous-flow technique. A first example involved conjugating a

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• (Scheme 4). The synthesis started from commercially available methyl (S)-3-hydroxy-2-methylpropanoate (21), which was converted to alcohol 22 by the known method [22]. Alcohol 22 was treated with 1-phenyl-1H-tetrazole-5-thiol/DEAD/PPh3 to furnish the corresponding PT-sulfide, which was oxidized with H2O2

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• circulation and extracellular milieus, but are prone to cleavage in a reductive environment through dithiol–disulfide exchange reactions forming two corresponding thiol end-group bearing moieties [27][28]. The cleavage reaction is relatively fast and can take place within minutes to hours. This is

• transition temperature (Tg), swelling behavior, and cloud points (Tc) of the thiol-bearing copolymers after cleavage were investigated. Although our results show only preliminary investigations, this hydrogel system with its redox-responsive behavior and polycationic structure could be a promising system for

• disulfide bonds to thiol side-chains (Scheme 1b). The dissolved polymers were cross-linked again by the oxidation of the thiol groups to reform disulfide bonds using oxygen under basic conditions at 60 °C. As described above, it was crucial to use concentrated solutions, because only thiol groups of

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• ions [21][22]. As illustrated in Table 5, tetrahydrofuranol and tetrahydropyranol both undergo condensation with a simple thiol in the presence of Re2O7 to provide the monothioacetal in good yield; only traces of the S,S-dithioacetal were observed. The same reaction, when catalyzed by a Brønsted acid

• , required a higher catalyst loading and provided a lower yield of product accompanied by a greater amount of dithioacetal. Re(VII)-promoted reaction with thioacetic acid proceeded in much lower yield. As illustrated in Scheme 2, Re2O7 also promotes the reaction of an aldehyde with a thiol or a dithiol to

• transparent light yellow solution (Figure S1, Supporting Information File 1), addition of thiol to a mixture of Re2O7 and hemiacetal produces an opaque, black, solution that gradually becomes translucent but remains very dark (Figure S2, Supporting Information File 1). Attempted reaction with nitrogen

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• novel nanocomposite catalyst AuNPs@HS-CNC. The uniform, fine AuNPs were made by the reduction of HAuCl4 solution with thiol (HS-) group-functionalized CNC films. The AuNPs@HS-CNC nanocomposites were examined by X-ray photoelectron spectroscopy (XPS), TEM, ATR-IR and solid-state NMR. Characterizations

• synthesized by using a modified procedure reported by Tingaut et al. Only the method of thiol functionalized CNC support (HS-CNC) is different from that reported by MacLachlan et al. (see Methods for the details about the catalyst preparation). Structure characterizations The XPS spectra (Figure 1

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium

• carbonotrithioate. The reaction conditions are reasonably simple and yields were very good. Keywords: Appel reagent; carbon tetrabromide; glycosyl hemiacetal; glycosyl thiol; thioglycoside; triphenylphosphine; Introduction Thioglycosides (1-thiosugar) are widely used glycosyl donors in glycosylation reactions [1

• , instability of the starting materials (glycosyl bromides, etc.), multiple steps, unsatisfactory yields, use of metallic salts, use of expensive reagents, pregeneration of glycosyl isothiouronium salts, etc. Similar to thioglycosides, glycosyl thiol derivatives are useful intermediates for the synthesis of

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• purification with crotylamine under microwave heating conditions to provide 15. Reaction of 15 with potassium ethyl xanthogenate, again under microwave heating conditions, led to the bicyclic thiol 16. Without purification, 16 was added to 1-bromo-3-phenylpropane in the presence of potassium carbonate to