Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• reaction mechanism starts with the oxidative addition of the diaryliodonium salt 1 to copper(I) iodide affording the Cu(III) species A, releasing aryl iodide 2. Coordination of the disulfide 6 to the metal centre leads to complex B, followed by the base-induced formation of arylcopper sulfide complex C and

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• which may cyclize through the formation of intramolecular disulfide bonds [39]. The most commonly used linear peptides and cyclic peptides that can be delivered inside cancer cells via endocytosis and one that smuggles into glioma tissues via transcytosis (angiopep-2) are presented below: Arginine

• /or in the acidic cellular compartments of cancer cells and consequently release the active drug. Additionally, disulfide linkers are often adopted in PDCs, since they are cleaved by reducing agents like cysteine and glutathione, present in high concentrations in malignant cells. Linkers bearing

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• polypeptide chain which is cleaved by a protease to give two subunits, A1 and A2, remain held together by extensive non-covalent forces and a single interchain disulfide bond [16]. The A2-subunit acts as a linker between the toxic A1-subunit and CTB which is the delivery vehicle that can transport the complex

• the cytosol. Following arrival in the ER, protein disulfide bond isomerase can reduce the disulfide bond between A13 and A2, releasing the A1 protein and causing the A12 and A13 domains to unfold [17]. The protein is then recognised by the cell as a misfolded protein and is exported into the cytolsol

• to come. a) Ribbon and b) surface depictions of the cholera toxin: A11 domain in light blue; A12 domain in dark blue; A13 domain in purple; cystine disulfide in orange; A2 peptide in green and B-subunit in red. Figure prepared using the PyMOL programme from Protein Data Bank file 1XTC.pdb. a

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

• intracellular abundant GSH. In this context, two classes of reduction-responsive units, disulfide-bond and benzyl-containing groups, were mainly introduced in prodrug-based ONs. Modifications at the internucleotide linkage Masking the negative charges of native phosphates typically improves cell penetration of

• internucleotide linkage [13]. It was shown that the stability in aqueous buffer and deprotection rates in the presence of GSH were influenced by the nature of substituents (Cl, NO2) on the benzene ring. More recently, Urata et al. reported a reduction-responsive modification containing a typical disulfide bond

• within a robust cyclic disulfide moiety [14]. Several modified ONs containing the cyclic disulfide trans-5-benzyl-1,2-dithiane-4-yl moiety have been synthesized using the corresponding thymidine phosphoramidite. Although they exhibited strong stability in serum and penetrated cells more efficiently

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• disulfide linker in the cytoplasm. In another example, Perrin and co-workers conjugated the N-propargylasparagine of an amanitin analog to a cycloRGD integrin ligand (cyclo[RGDfK]) using a copper-catalyzed azide–alkyne cycloaddition [8]. The conjugates were tested in the U87 glioblastoma cell line, but only

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• lab, we have been developing a strategy for solid-phase trinucleotide synthesis involving a disulfide linkage to the support (CPG or polystyrene), which can be cleaved under reductive conditions without harming nucleobase and phosphate protecting groups. The disulfide bridge is generated through the

• reaction of a 3'-O-methylthiomethyl-functionalized nucleoside with 2-mercaptopropionic acid and subsequent coupling to amino-functionalized CPG or polystyrene. After assembly of the trinucleotide on the support, the disulfide bridge is cleaved by treatment with dithiothreitol (DTT) [38] or tris-(2

• well suited to it. Also the solution-phase synthesis of protected trinucleotide building blocks has been described in the literature [21][22][23]. In an initial attempt, thymidine as a start nucleoside was tethered to a precipitative tetrapodal soluble support via a disulfide-linker [21] (Table 1

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• binding domain and the stem part consisted of a chimeric PNA–DNA hybrid linked together by a disulfide bond (Figure 4). The chimeric beacon was immobilized to a microtiter plate via a biotin tag and was employed for the detection of PCR amplicons of rDNA from Entamoeba histolytica [41]. The use of PNA

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• chlorides, chloroacetyl chloride, isothiocyanate and carbon disulfide under appropriate reaction conditions (Scheme 52). Hassan et al. [130] reported the synthesis of various pyrazolo[3,4-d]pyrimidine derivatives 193 (Scheme 53). 5-Aminopyrazole-4-carboxylic acid 190 on refluxing in acetic anhydride

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

• disulfide, thioamide derivatives and sulfides Disulfides and thiosulfates Sulfoxides Sulfinic acids, sulfinate salts and sulfinamides Sulfonyl halides, sulfonyl hydrazines, thionyl chloride and sulfur dioxide C–S bond formations initiated by irradiation with light of wavelengths shorter than 380 nm or by

• . Carbon disulfide Formation of 1,3-oxathiolane-2-thiones In 2016, Yadav and co-workers reported a photoredox-catalyzed C–S bond formation with carbon disulfide (CS2) as starting material (Scheme 30) [65]. The reaction of CS2 with styrenes under visible-light irradiation and Eosin Y as organic

• diazonium salts and dimethyl disulfide (Scheme 37) [72]. They applied Eosin Y for the photoreduction of aryl diazonium salts, in order to generate the respective aryl radicals. Radical addition to the nucleophilic disulfide forms a stabilized trivalent sulfur-centred radical. Oxidation of this intermediate

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

• SPAAC in their one-pot stepwise preparation of GAuNPs, and then used those particles as supramolecular glycoprobes for the rapid serological recognition of a cancer biomarker. Firstly, ligand exchange was performed on Cit-AuNPs by reaction with a THF solution of a cyclooctyne disulfide and an aqueous

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• this proposed mechanism, bis(trifluoromethyl)disulfide (CF3SSCF3) was generated but its possible role in the trifluoromethylsulfenylation was not evoked. A slight tuning of the reaction conditions, including notably a replacement of NaI by n-Bu4NI, as well as the increase of reagents quantities

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

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• /bjoc.13.247 Abstract A one-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates by the reaction of secondary amines, carbon disulfide and Togni’s reagent is described. The reactions proceed in moderate to good yields. A similar reaction using a primary aliphatic amine

• 2001 Naumann and co-workers [36] have published a reaction of tetraethylthiuram disulfide with perfluoroorganosilver and perfluoroorganocadmium reagents proceeding most probably by a radical mechanism (Scheme 1a). This method suffers from several drawbacks such as extra reaction steps for the

• preparation of the thiuram disulfide and the use of expensive and environmentally problematic heavy metals. These observations prompted us to investigate the reaction of in situ prepared dithiocarbamic acid with Togni's reagents as a new route to S-trifluoromethyl dithiocarbamates (Scheme 1b). Results and

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• β-aminoalcohols by β-aminothiols in reactions with dialkyl dicyanofumarates E-1 led, unexpectedly, to products containing a disulfide group together with enamine units. For example, the reaction with cysteamine (92) with E-1a in CH2Cl2 at room temperature gave the disulfide 93 in 42% yield [72

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• ]. The group of Ravoo also conjugated arylazopyrazoles to amphiphilic cyclodextrin derivatives that form vesicles triggered by light [17]. A star-shaped polycationic CD derivative with many breakable, intrinsic, disulfide linkages forms nanoparticles with messenger RNA and drugs and is particularly

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• therefore the variation in the carbonyl functionality may have implications in drug design. Moreover, Asu and its congener 2-aminopimelic acid have been used as ethylenic equivalent of a disulfide linkage [4]. Other applications of Asu in peptide engineering and as a building block are of notable importance

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• glycosylation has been proposed (Scheme 15). Addition of p-TolSCl to the mixture of donor 76 and AgOTf forms p-TolSOTf, a powerful electrophile that can electrophilically add to the anomeric sulfur atom of 76 forming disulfonium ion 77 (step 1 in Scheme 15). After ejection of the ditolyl disulfide, 77 can

• greatly disfavors the formation of a positively charged dioxalenium ion while the electron-donating benzyl (Bn) group can stabilize the dioxalenium ion. Donor 87 presents an intermediate case. The absence of the disulfonium ion 81 following the donor activation confirms that the disulfide does not

• /AgOTf (Scheme 17). This is presumably due to the inertness of the ditolyl disulfide side product from p-TolSCl/AgOTf promoted activation, which does not interfere with glycosylation. The p-TolSCl/AgOTf-promoted preactivation glycosylation has been successfully applied to the total synthesis of complex

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• (reaction 1, Scheme 3). In addition, sulfonyl hydrazine 2b gave disulfide 6 under the same conditions (reaction 2, Scheme 3), suggesting that chromone 5 and disulfide 6 might be key intermediates in the domino reactions. Moreover, the same reaction in the presence of TEMPO gave no formation of 6, indicating

• first take place via the promotion of IO3− to afford intermediate 7, and the IO4− generated therein returns to IO3− in the presence of the simultaneously generated hydrogen in this step. According to a known route [44][45], 7 can be further reduced to yield disulfide 6. The disulfide is capable of

• with radical 8 may also provide dithiolated intermediate 10 (path b). And the elimination of the α-hydrogen and β-sulfur gives target product 3i and thiophenol 11. The thiophenol could be easily reoxidized into disulfide 6 even under air atmosphere [48][49], which enables the recycled production of

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

• % 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

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• structure in a one-pot two-step mechanochemical sequence. Another typical synthetic method for the preparation of thioureas, particularly if the desired isothiocyanate is not available, is the condensation of an amine with carbon disulfide [36]. This reaction proceeds through the formation of a

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

• and Ni/RGO-60) were also tested (Table 1). All reactions were carried out under a N2 atmosphere to avoid oxidative dimerization of thiols to disulfide [50]. Solvent optimization was started with water (Table 1, entry 1) followed by toluene (Table 1, entry 2) and isolating diaryl sulfide only 6–8

• suppressing the overall yield of the thioether (Table 1, entries 5 and 6). Without using any base, the yield was 74%, while the use of KOH as a base afforded the thioether in 83% yield (Table 1, entries 7 and 8). Formation of the diphenyl disulfide via oxidative dimerization of benzenethiol was noticed (15

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• vesicles could also be linked to an internal chemical reaction. In this case [101], the irradiation of membrane-located photosensitizers stimulated the formation of disulfide bonds in small hydrophilic molecules in the vesicle lumen, which then migrated subsequently into the boundaries provoking changes in

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• related reductively cleavable disulfide-linked support 7 [50]. Synthesis of oligodeoxyribonucleotides by phosphoramidite chemistry As mentioned above, phosphoramidite chemistry is nowadays the method of choice for the solid-supported synthesis of oligonucleotides both in small and large scale. The first

• precipitative PEG support was applied, tetraethylthiuram disulfide (TETD; 0.5 mol L−1 in MeCN; 10-fold excess) was used as the sulfurization reagent [66] instead of tert-butyl hydroperoxide used for the oxidation in the synthesis of unmodified ODNs [51]. On using 2.5 equiv of phosphoramidites for coupling, a

• was 99% on using 3.0 equiv of the dimeric building block [67]. The resulting phosphite triester was after each coupling oxidatively sulfurized with a 10-fold excess of diethyldithiocarbonate disulfide (DDD) [68]. The capping step after each sulfurization was carried out at 0 °C to avoid cleavage of

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

• , Zn–HCl, catalytic hydrogenation (H2–molybdenum disulfide) and metal hydrides like LAH [12][13][14][15][16][17]. These methods, however, suffer from disadvantages like slow reaction rates, poor product yields, involvement of expensive and harsh reagents [16] and predominant side reactions leading to

• reaction. Most importantly, the reaction furnished only thiols as the final product with no disulfide formation. Interestingly, no similar reaction of thiocyanates was observed with other thionating agents like Lawesson’s reagent and PSCl3 and the reactant was recovered quantitatively in those cases. In