(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• loading. The authors proposed a bifunctional mode of activation. More specifically, the thiourea moiety activates the maleimide through hydrogen-bonding and the tertiary amine recognizes the thiol group, again through hydrogen-bonding, and orients the thiol attacking from the Si-face of the maleimides 52

• were obtained in good to excellent yields (up to 96%) and moderate to excellent selectivities. In 2010, Chen, Xiao and co-workers described a domino sulfa-Michael–Michael reaction catalyzed by the novel multifunctional thiourea 171 (Scheme 56) [77]. The cascade is initiated by the addition of thiol 173

Optimized methods for preparation of 6^I-(ω-sulfanyl-alkylene-sulfanyl)-β-cyclodextrin derivatives

• Eva Bednářová,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2016, 12, 349–352, doi:10.3762/bjoc.12.38

• Prague, Hlavova 8, 128 43, Prague 2, Czech Republic 10.3762/bjoc.12.38 Abstract A general high-yielding method for the preparation of monosubstituted β-cyclodextrin derivatives which have attached a thiol group in position 6 is described. The thiol group is attached through linkers of different lengths

• disulfide can be used directly for functionalization of a gold surface, but its reduction to thiol was not described. In any case, the amide-containing derivative might not be stable enough under basic conditions needed for the polydopamine derivatization by the thiol. Besides, the common problem with the

• (disulfides 6a–g) are quite stable compounds and were prepared in quantitative yield just by bubbling air through the water/methanol solution of the thiol which was basified by addition of aqueous ammonia. The disulfides 6 can be used, as well as the thiols, for the attachment of the cyclodextrin cavity to a

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• occurrence of multiple-drug-resistant (MDR), extensive-drug-resistant (EDR), and totally drug-resistant (TDR) pathogens has increased the need for new drug candidates for treating tuberculosis. Mycothiol (MSH) 1 is the main low-molecular-weight thiol found in most actinomycetes, including Mycobacteria and

• analyses and computational calculations [11][12]. Recently, N-acyl variants of MSH homologs, such as formyl, propanoyl, and succinoyl, have been reported [13][14][15]. Gram-negative bacteria and most Eukaryotes utilize glutathione as a low-molecular-weight thiol for maintaining a reducing environment in

• the cytosol. Gram-positive bacteria including actinomycetes lack glutathione, instead, MSH is found as the major low-molecular-weight thiol. It is considered that MSH is required for maintaining a reducing intracellular environment in Gram-positive bacteria, similar to glutathione in eukaryotes 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

• histidine were not among the active site residues of the parent (or wild type) enzyme but appeared in several of the new variants, thus introducing a thiol, polar or basic group where previously none existed. More bulky aromatic side chains in libraries I and II were often substituted for smaller side

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• . Recently Greaney and co-workers discovered that thiols 45 were also suitable donors with photoactivated TiO2 [67]. The thiol radical cations, formed on hole capture by the thiols, lost protons and generated thiyl radicals (Scheme 10). Benzenethiol, thiophenols and n-alkylthiols all afforded reduced alkene

One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2015, 11, 1265–1273, doi:10.3762/bjoc.11.141

• many uses in organic synthesis as intermediates, mild acyl transfer agents and thiol sources [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Thioesters can be synthesized in the laboratory by means of different methods using diverse reagents and substrates [20][21][22][23][24][25

• ][26]. The reaction of active carboxylic acid derivatives with thiols [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and the coupling of thiols with carboxylic acids using activating agents [42][43][44][45] have been mainly used for the synthesis of thioesters in organic synthesis. Thiol

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• bearing a 2-cyanoethyl-protected thiol The 2-cyanoethyl protecting group offers a convenient means of synthesising MPTTFs where one or both of R1 and R2 are thioethers. When only simple alkyl thioethers are targeted, it is often more effective to incorporate these moieties prior to the cross-coupling step

• ) (EtO)3P, 120–135 °C, 1–4 h, 70–87%. Deprotection and methylation of cyanoethyl-protected thiol moieties on MPTTFs as reported by Jeppesen et al. [25]. Reagents and conditions: a) (i) 1 equiv CsOH·H2O, MeOH, THF, rt, 1 h, (ii) MeI, THF, rt, 30 min; b) (i) 1 equiv CsOH·H2O, MeOH, THF, rt, 1 h, (ii) MeI

• , THF, rt, 45 min, (iii) 1 equiv CsOH·H2O, MeOH, THF, rt, 1 h, (iv) MeI, THF, rt, 30 min. Deprotection and alkylation of cyanoethyl-protected thiol moieties on MPTTFs using CsOH·H2O or DBU. Reagents and conditions are detailed in Table 2. Deprotection and N-arylation of tosylated MPTTFs. Reagents and

Single-molecule conductance of a chemically modified, π-extended tetrathiafulvalene and its charge-transfer complex with F₄TCNQ

• Raúl García,
• M. Ángeles Herranz,
• Edmund Leary,
• M. Teresa González,
• Gabino Rubio Bollinger,
• Marius Bürkle,
• Linda A. Zotti,
• Yoshihiro Asai,
• Fabian Pauly,
• Juan Carlos Cuevas,
• Nicolás Agraït and
• Nazario Martín

Beilstein J. Org. Chem. 2015, 11, 1068–1078, doi:10.3762/bjoc.11.120

• wire using two thioacetate anchoring groups [13], most of the TTF derivatives synthesized for this purpose have been functionalized with sulfur atoms as alligator clips. These belong either to a fused ring on the TTF [14], or to a chain covalently connected to the TTF core bearing a thiol group at the

• complex and one of the terminal thiol groups. We observed a similar feature for the neutral molecule (see Figure 4b and Figure 4c) although for the neutral molecule, this signal was never very reproducible. The low group, on the other hand, fits well with conductance taking place across the whole molecule

• (i.e., thiol to thiol). We calculate an S–S distance of 2.4 nm for the CT complex (substituting the dihydroanthracene core of compound 5 for anthracene). We estimate the amount of gold retraction to be 0.5 nm, which then gives a real Au–Au separation of 1.64 ± 0.30 nm for the mean breaking distance of

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• gold coated SFM cantilever probes and surfaces using thiol chemistry (for details see Experimental section below). The interaction between gold and SH-groups is known to withstand rupture forces in the range of 1 to 2 nN [38], followed by the formation of a monoatomic gold nanowire that finally leads

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

• ]. The first method reported was leveraged on a nucleophilic coupling between readily available glycosyl thiol (obtained in one step by treatment of a native carbohydrate with Lawesson’s reagent [37]) and a chloroacetamide-functionalized PNA (Scheme 7) [38][39]. Using this method, we have shown that

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• defensive low molecular weight thiol [7]. 2-C-acetamide and 2-C-acetonyl carbohydrate derivatives have also been reported to serve as inhibitors of the biosynthesis of lipids [8][9] and cell surface engineering [10], respectively. The main synthetic protocols for the synthesis of 2-C-branched sugars involve

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• related compounds, such as various amino alcohols and the thiol-functional amino acid cysteine. While the basic methodology underlying this approach has been known for decades, it has evolved through recent developments connected to amino acid-derived chiral organocatalysts to become a more widely

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• basic condition. 4-Amino-2-sulfanylphenol derivatives The class of 4-amino-2-sulfanylphenols is obviously an outlier among the reviewed compounds, as the 2-sulfanylphenol substructure is not a structural element in natural products. The vast majority of thiol groups in secondary metabolites derive from

• the amino acid cysteine, producing aliphatic secondary metabolites with thiol functionalities instead of phenolic ones. Nevertheless, this class contains thio-analogs of the naturally occurring o-catechol substructure, and thus, it has been included in this review. Zhang and Xu et al. [51] have

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• is an effective photocatalyst in oxidatively induced photoredox transformations where less strongly oxidizing complexes (e.g., 1) are not successful. For instance, we have reported that 2 is uniquely capable of promoting radical cation mediated Diels–Alder cycloadditions [12], radical thiol–ene

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• including azide–alkyne cycloadditions [9][10], Diels–Alder reactions [11][12], maleimide–thiol reactions [13], thiol–ene additions [14], and imine/oxime conjugations [15]. In this article we demonstrate that dihalocarbenes can be used to generate dihalocyclopropanes on olefin terminated SAMs. We recently

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• nucleophilic annulation process (Scheme 1b) [24]. But this method involves a two-step process and the usage of two different metal salts may complicate further processing. The direct design of a Pd or Cu-catalyzed one-pot synthesis of benzo[b]thiophenes from 2-bromoalkynylbenzenes and a thiol derivative has

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