Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• simplified n-pentyl and cyclohexylmethyl model compounds towards thiol and amine nucleophiles as well as their reactivity towards a model protein target, lysozyme. Results and Discussion Preliminary studies of the reactivity of onchidal (6) towards 1-pentanethiol or 1-pentylamine were undertaken in CDCl3

• solvent in an NMR tube. Somewhat to our surprise, no reaction was observed with 1-pentanethiol, even with incubation in the presence of excess thiol for one week [14]. In contrast, incubation with excess 1-pentylamine rapidly afforded a mixture of products, as identified by changes in the 1H NMR spectrum

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• deprotonation of the OH group and subsequent chloride loss of 4 an o-quinoid structure 9 is formed in situ, that quickly reacts with the deprotonated thiol 10 via Michael addition (Scheme 3, route A) [28][29][30]. However, as aromatic thiols at the benzylic position are good leaving groups, conversely β

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• and thiol functional groups. The reversible shuttling movement of the macrocycle between two different recognition sites on the molecular thread can be driven by external acid and base. This kind of rotaxane bearing functional groups provides a powerful platform for preparing stimuli-responsive

• the presence of Grubbs’ catalyst and thiol groups irradiated by UV light. Besides, the shuttling movement of the DB24C8 macrocyclic ring was confirmed by 1H NMR spectroscopy. Results and Discussion The structures of the two states of [2]rotaxane R1 are shown in Scheme 1. In the target structure [2

• . The naked alkenyl groups could react with other functional groups such as alkenyl and thiol groups to prepare stimuli-responsive polymers. Besides, the introduction of long alkyl chains makes the polymers easier to form gels. This kind of functional rotaxane enriches the species of building blocks to

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• photocatalysts in cooperation with a disulfide cocatalyst, which is converted to the corresponding thiol and serves as a source of hydrogen atoms for the reduction of the double bond (Scheme 17) [62]. The scope of the reaction is not particularly broad; electron-withdrawing groups such as pyridyl or

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• synthesis, otherwise subsequent steps are complicated. Synthetic chemists, armed with various elegant artificial orthogonal bond formations, including alkyne–azide cycloaddition [27][28][29][30][31][32][33][34], thiol–ene ligation [35][36][37][38], Staudinger ligation [39][40], inverse-electron-demand Diels

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• since sulfur, in the form of the sulfate ion, is the second most abundant anion in sea water after chloride. As part of natural products, sulfur can appear in a multitude of combinations and oxidation states: thiol, sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal

• organic compounds are, like all natural products/secondary metabolites, staggeringly diverse with respect to their natural source and their level of structural complexity. As part of their molecular architecture, sulfur can appear in the form of various functional groups and oxidation states: thiol

• , sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal, hemithioacetal, various thioesters, thiocarbamate and isothiocyanate [3]. The three simplest sulfur-containing natural products are perhaps, (E)-2-butene-1-thiol (1), the principal ingredient of the repulsively malodorous

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

• -labeled adenosine tends to be sluggish and incomplete [25]. Furthermore, the protection group present in 22a–27a also shields the nitroxide precursor if subsequent enzymatic ligation steps in thiol containing buffers are required [43]. A single case has been reported earlier of an O-acetyl protected TEMPO

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• -thiol as bridging ligands coordinating two Pt(II) centers in a monodentate fashion, Zhu and co-workers have reported on dimeric structures, namely 2 and 3, exhibiting an interaction between the two metallic centres (Pt···Pt distance of ca. 3 Å) (Figure 2). The appearance of a triplet metal–metal-to

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• with cysteamine into the protected thiol 8 [39]. Steglich esterification [40] with different free acids led to nine saturated PCEs 10a–i, four monounsaturated acids (11a–d), 3-OH-C10:0-HSL PCE (12), and 2E,11Z-C18:2-PCE (13) after deprotection with acetic acid [41]. Although compounds 10–13 can be

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

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• ]. Thiol functionalized PEG blocks were immobilized on Au NPs. PS segments improved the stability of the system and provided the necessary hydrophobic environment that is required to undertake the reduction reaction in water. The outcome of using Au@PEG-PS as nanoreactors was compared to those resulting

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

• ’-O-acetylthiomethyl-containing RNA, produces various 2’-O-alkyldithiomethyl (RSSM)-modified RNAs bearing lipophilic or polar groups through a thiol disulfide exchange reaction with alkyldisulfanyl-pyridine derivatives (Scheme 3). In a preliminary evaluation, the RSSM modifications were shown to

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• preparation of sulfides. Non-photocatalytic procedures apply the so-called radical thiol–ene or radical thiol–yne reactions for efficient cross-coupling of thiols with olefins [24][29][30]. In 2013, Yoon and co-workers developed a photoredox-catalyzed version of the radical thiol–ene reaction (Scheme 2) [31

• of 4 equivalents of the thiol is needed for the reaction. The authors addressed this limitation in a later report (vide infra). Functional groups like alcohols, Boc-protected amines, carbonyls, esters and halides are tolerated. One year later, Yoon and co-workers described a redox mediator concept

• , which was applied to their photocatalytic radical thiol-ene reaction (Scheme 3) [32]. While the photooxidation of aliphatic thiols by excited [Ru(bpz)3](PF6)2 is thermodynamically feasible, this process is kinetically hindered. Therefore, relatively low yields are observed or the amount of thiol has to

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• comprised of AuNPs with the surface Au atoms covalently attached to thiols of thiol-terminated oligosaccharides [8]. It was found that GAuNPs could be used as mimics of the glycocalyx to study both carbohydrate–carbohydrate and carbohydrate–protein interactions [9][10]. Other applications of GAuNPs, as

• thiol end group, which is generally attached to the reducing terminus by a linker (Figure 1a) [8][14][17][18][19][20][21][22][23][24][25][26][27]. The second method is a ligand exchange reaction involving the replacement of the ligands on pre-formed AuNPs with thiol-linked carbohydrate derivatives

• (Figure 1b). The most frequently employed approach here is to first synthesize citrate-stabilized AuNPs (Cit-AuNPs) [28], and then to replace the citrate ligands with the desired thiol-linked carbohydrate derivatives [29][30]. Ligand exchange on the AuNP surface is driven by the higher binding affinity of

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• cycloaddition, CuAAC and RuAAC), the thiol–yne reaction, Diels–Alder reactions and the Sonogashira cross-coupling. While amino acids with a terminal alkyne in the side chain are well-known, the synthesis of their correlates where the carboxy group is replaced by a terminal alkyne is still tedious. Nevertheless

• propargylamines without an acidifying Cα-substituent. Synthesis of propargylamines containing polar or acidic functional groups The synthesis of propargylamines with polar substituents to mimic polar amino acids such as serine (alcohol), cysteine (thiol) or glutamine (carboxamide) requires special protective

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