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

• PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method. Keywords: amination; bromination; carboxylation; mechanochemistry; poly(ethylene glycol); solid state; thiolation

• % for Mn = 750 and 2000 Da, respectively. In this reaction, thiol was obtained as major product, with a small portion of disulfide as byproduct. Yield of 48% −SH + 7% –S–S– and 69% –SH + 9% –S–S– were measured for Mn = 750 and 2000 Da, respectively. In the 1H NMR spectra, the mPEG–SH was clearly

• identified by a triplet at 2.86 ppm, characteristic of methylene hydrogens germinal to thiol, while the corresponding peak of mPEG–S–S–mPEG appeared at 2.72 ppm (Figure S4, Supporting Information File 1) [20]. The formation of the disulfide derivatives is explained by the reaction being performed under

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• reported O-GT to catalyse S-glycosylation on thiol acceptors [30]. Genetic engineering of this enzyme has also led to S-GT activities on several thiols. UGT73AE1 from Carthamus tinctorius was able to transfer glucose on a wide range of acceptors, including a S-containing compound, dichlorothiophenol [31

• ]. More recently, BcGT1 from Bacillus subtilis was shown to efficiently catalyse the glucosylation of thiol-containing acceptors [32]. C-Glycosyltransferases For more than 50 years, C-glycosides have been identified in plants [33][34] as secondary metabolites. At least 5 families of aromatic aglycones

• are named thioligases [65]. Based on the mechanism, here the formation of the glycosyl–enzyme intermediate requires the use of an activated glycosyl donor, such as dinitrophenyl or azide glycosides, and the glycosylation step needs stronger nucleophiles such as thiol derivatives. The choice of the

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• with comparable conversions (Table 1, entry 15). We then extended the optimized reaction conditions (as in Table 1, entry 4) using Ni/RGO-40 to diverse functionalized aryl halide/thiol combinations. The results are indeed encouraging and summarized in Table 2. Both coupling partners, i.e., the

• /RGO-40 A mixture of aryl halide (1 mmol), thiol (1.2 mmol), potassium carbonate (1.2 mmol), Ni/RGO-40 catalyst (22 mg; Ni content is 8.8 mg, 0.15 mmol, 15 mol %) in DMF (3 mL) were taken in a 15 mL sealed tube, flashed and filled with N2 gas and quickly screw-capped. The reaction mixture was then

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• reported for the Grubbs–Hoveyda type [29][47] or copper complexes [10] (Scheme 1). FhuA ΔCVFtev was dissolved in a solution containing 1.25% SDS. The state of FhuA ΔCVFtev is partially unfolded. The catalyst 1 easily accesses the thiol group (Cys545, numbering based on FhuA WT with PDB ID 1BY3 [24

• ]) introduced for maleimide thiol coupling and a high coupling efficiency is achieved (Figure S2, Supporting Information File 1). After coupling, the excess catalyst is removed by washing the protein residue with THF. The dried biohybrid conjugate 2 is dissolved in water and refolded. As refolding reagents, the

• of the cysteine function of 2 (Cys545) using the fluorescence dye ThioGlo® 1 (fluorescent thiol reagent, Figure S2, Supporting Information File 1). More than 90% of the cysteines are occupied, showing a very high coupling efficiency of the rhodium catalyst. Further, the biohybrid conjugate was

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

• glycosides: A potentially attractive strategy for a 1,2-cis glycosylation has been described by Baker and colleagues [56] and employs the use of a deprotected thiol glycoside in the presence of a large excess of Lewis acid (TMSOTf) and N-iodosuccinimide (NIS). Although the stereoselectivity of the reaction

• stereoselective when a 2-deoxygalactose analog is used as the donor and propargyl alcohol as the acceptor (Table 4, entry 13). It is crucial to mention that the synthesis of the parent thiol glycoside donors is a multistep process and the authors did not provide yields for the synthesis of any of the glycosyl

• thiol in moderate to excellent yield. They proposed that the oxazoline intermediate blocks access to the α-face of the molecule, hence accounting for the excellent stereoselectivity of the reaction. They then demonstrated the power of this method as a ligation strategy. The protected thiol can be

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• building blocks consist of an aromatic core that is functionalized with two thiol groups and a peptide chain (Figure 12a). Building block 1 and 2 are very closely related to each other and differ only in a single amino acid of the peptide chain. These peptide building blocks can then be oxidized to form

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• required by reported methods, and provides an attractive alternative to the existing methods for the conversion of organic thiocyanates to thiols. Keywords: dithiocarbamate; phosphorus pentasulfide; thiocyanate; thiol; toluene; Introduction Thiols constitute an important group of sulfur-containing

• thionation of the thiocyanate functionality with P2S5 to give the corresponding dithiocarbamate derivative which, in presence of residual phosphoric acid of P2S5, decomposes to give the corresponding thiol, in analogy with the acidic hydrolysis of S-thiocarbamates [21]. Although, we were not able to isolate

• the S,S-dithiocarbamate intermediate from the reaction between thiocyanate and P2S5, its formation was indirectly confirmed by treating benzyl S-thiocarbamate, synthesized separately [22], with P2S5 under similar reaction conditions to give the corresponding thiol (80%). It could be believed that

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• Penadès and co-workers [15] is a modified Brust–Shiffrin method [17], based on the in situ Au3+ reduction by means of NaBH4 in the presence of thiol-ending neoglycoconjugates. Following this approach, a rapid synthesis of AuNPs characterized by elevated glycan density on the NP surface and a 1–10 nm

• the “thiol for thiol” ligand exchange method, which allows the superficial diversification by introducing small amounts of different ligands after the AuNP synthesis [11][12][18]. Recently, the Seeberger group reported a straightforward one-pot method to prepare glucose-stabilized ultrasmall AuNPs, by

• procedure for the immobilization of carbohydrates on the nanoparticles surface [27]. The AuNPs were firstly coated with a PFPA-thiol monolayer via a ligand-exchange reaction, then carbohydrates were immobilized by means of a photocoupling reaction. Glyco-gold nanoparticles: design and structural properties

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• disulfide bonds formed by the oxidized thiol groups of cysteine confer exceptional stability for the peptides and proteins where they are present [10]. Thus, a systematic study on the conformational behavior of L-Met and L-Cys can reveal unique properties about the formation of proteins and peptides that

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• have been investigated for the immobilization of a target molecule through a reaction with the terminal groups of the SAMs. The most common methods to covalently functionalize these materials involve the Huisgen cycloaddition between an azide and an alkyne [8][9], Thiol-Michael addition [10][11], amide

• previously observed by PM-IRRAS and contact angle measurements. In this work the S2p signal is particularly important because it allows the characterization of the SAM formation via thiol moieties and especially evaluating the conversion rate of the reaction since the XPS signature of the sulfamide moiety

• must be very different from the one of thiol moiety. The all four samples highlight a strong S2p3/2,1/2 doublet at 162.0 ± 0.1 eV (S2p3/2) (blue) characteristic of the thiolate-gold bond [50] with an additional XPS peaks doublet at lower binding energy of 161.1 ± 0.1 eV (green) attributed to

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• has not been reported. In this review, a brief overview is given of the recent advances in synthetic strategies for both phenols and aryl thiols. Keywords: aryl thiol; C–O bond; C–S bond; phenol; transition metal; Introduction Phenols and aryl thiols serve as both important intermediates in organic

• before the formation of copper complex. In 2016, the Wang and Shi group reported a CuI-catalyzed C–H hydroxylation of thiophenols, in which disulfide directed the hydroxylation [58]. Using aryl thiol and arylboronic acid as starting materials, C–H hydroxylation and C–S coupling sequentially occurred in

• methods for aryl thiol preparation was not observed. There may be two reasons which block the development of synthetic methods for aryl thiols: (1) Traditionally, sulfur was considered poisonous to transition metal catalysts [93][94]; (2) aryl thiols are very reactive forming intermolecular or

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• induced thiol–yne click reaction. Using this reaction, we could greatly enhance the CMP nanomembrane synthesis and further broaden the variability of the LbL approach. Keywords: click chemistry; conjugated microporous polymers (CMPs); microporous materials; nanomembranes; thin films; thiol–yne coupling

• catalyst-free thiol–yne coupling (TYC) reaction. TYC has gained large attention as a representative of the click chemistry concept [17]. In the TYC reaction, usually a photoinitiator creates thiyl radicals [18][19][20], which react with nearby alkyne moieties to form covalent sulfur–carbon bonds and vinyl

• radicals. Additional thiol moieties can undergo hydrogen transfer to the vinyl radical leading to thiyl radicals and vinyl sulfides. The vinyl sulfides can then undergo a thiol–ene coupling (TEC) reaction, leading to bis-sulfide species. TYC has been used for surface modification [21][22

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• of thiols [66]. Noël and co-workers set up a microflow system equipped with a mass flow controller (MFC) able to introduce pure oxygen as the oxidant to oxidize a solution of thiol containing 1% of Eosin Y. The flow stream was exposed to white LED light in order to activate the reaction, and a

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• nucleophilic attack by the terminal phosphopantetheine thiol of the ACP domain. Recent steady-state kinetic analysis of an AT domain sourced from DEBS module 3 (Figure 3) has provided evidence that the specificity for (2S)-methylmalonyl-CoA is expressed during the first half reaction of the ping-pong mechanism

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• the thiol groups of proteins in eukaryotes. In contrast, the Bacillus quorum sensing peptide pheromone, the ComX pheromone, possesses a posttranslationally modified tryptophan residue, and the tryptophan residue is isoprenylated with either a geranyl or farnesyl group at the gamma position to form a

• referred to as the farnesylation or geranylgeranylation of the thiol group of the C-terminal cysteine residue in peptides and proteins [4][5][6][7]. The isoprenylation of cysteine was first found in the peptide pheromones of basidiomycetous yeast [8][9][10]. Two peptide pheromones, tremerogen A-10 and

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• from I followed by electron delocalization and the overall formation of cyclohexyl isothiocyanate (4) via C–S bond cleavage and the formation of quinazoline thiol anion II having a negative charge concerted on the nitrogen atom. The protonated cyclohexylamine in the previous step will transfer this

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• stoichiometry to the ball mill reaction gave complete and clean conversion of CldA (1a) into MobSdA (2a) monitored by TLC within 1 h in a previously unused steel vessel (Table 1, entry 1). The efficiency of chloride displacement from CldA (1a) was compromised in the presence of fewer equivalents of thiol (Table

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• methyl 10-undecenoate which was subjected to a thiol–ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their

• lipoconjugates of phenolic acids is reported. The synthetic route was simple with product yields in the range of 84–86% over three steps. The lipid part, methyl 10-undecenoate was subjected to a thiol–ene reaction with cysteamine hydrochloride and the resulting intermediate was conjugated with the phenolic acid

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• nm, respectively, as well as a broad minor peak at λ = 548 nm (Figure 2a). The peaks at λ = 420 and 450 nm are caused by different protonation states of the thiol side chain of the proximal heme ligand cysteine: P450 enzymes displaying a protonated thiol ligand (as indicated by a peak at λ = 420 nm

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• derived from monosaccharides by reduction of the carbonyl group, by oxidation of at least one functional group at the end of the chain in carboxylic acid, by replacement of one or more hydroxy groups by a hydrogen atom, an amine, a thiol or any similar group are also called carbohydrates. Carbohydrates

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• antioxidants in polymers [6]. They are typically synthesized through the condensation of a thiol with organic halides under strong basic conditions [7][8][9], but due to the high toxicity of alkyl halides the introduction of new methods of access to this kind of materials is desirable. The ideal reaction from

• totally unreactive. As far as the thiol is concerned both aromatic and cyclic thiols gave excellent results. The attempt to carry out the reaction in a solvent-free mode gave surprising results. The reaction was slower but selectivity was still very high. Results are reported in Table 2. Aromatic and

• nucleophilic substitution mechanism: the higher the electronic density on the carbinol C atom, the higher the reaction rate. When the electronic density is somewhat lower, competitive formation of the ether occurs but subsequent nucleophilic addition of the thiol to the ether restores a very high selectivity

Synthesis of three-dimensional porous hyper-crosslinked polymers via thiol–yne reaction

• Mathias Lang,
• Alexandra Schade and
• Stefan Bräse

Beilstein J. Org. Chem. 2016, 12, 2570–2576, doi:10.3762/bjoc.12.252

• Eggenstein-Leopoldshafen, Germany 10.3762/bjoc.12.252 Abstract Herein we report the syntheses of two porous hyper-crosslinked polymers (HCPs) via thiol–yne reaction with rigid tetrahedral and pseudo-octahedral core structures. Sorption measurements with nitrogen gas at 77 K revealed BET-surface areas up to

• 650 m²/g. Those networks also showed a high thermal stability as well as insolubility in common organic solvents. Keywords: three-dimensional; porous hyper-crosslinked polymers; thiol–yne; Introduction The synthesis of different organic networks has been previously reported. Among them, especially

• tetraphenylmethane-based networks by another click reaction, the thiol–yne reaction [14][15][16][17][18][19]. This reaction type has been known for several decades and relived a renaissance in the past decade, especially in material sciences [20][21][22][23][24][25][26][27][28][29][30][31][32], due to its mild, and

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• recently investigated [8]. Up to now, it was not possible to polymerize MLA via ring opening [9]. Only indirectly, unsaturated polylactide carrying vinyl side groups can be obtained through a copolymerization of chlorolactide with L-lactide followed by subsequent dehydrochlorination [10]. Recently, thiol

• attack of the thiol takes place. This can be clearly seen in the 1H NMR spectra (Figures S18 and S19, Supporting Information File 1). Thioacetic acid was used as a potential chain-transfer agent due to its lower nucleophilicity. However, a complete thiol-Michael addition can be seen in Figure 8 (not full

• conversion of MLA due to the impurities of thioacetic acid like disulfide and acetic acid). In this context, the iodine catalyzed thiol-Michael addition was investigated [11]. Controlled radical polymerization of MLA via RAFT Since MLA acts as a vinyl monomer, it was also interesting to evaluate the

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• as sodium hydride, to activate the thiol group of 3-mercaptopropionic acid (MPA) and N,N-dimethylformamide (DMF) [16]. In the reaction solution and particularly on larger scales (from 10 g to kilo lab scale), impurities that arise from incomplete conversions, product and byproduct decomposition as