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

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

• observed for this compound. The study of 2 through NMR spectroscopy was not carried out in the present work because it was not possible to obtain the corresponding free amino acid derivative. When in solution, cysteine forms a dimer through disulfide bonds between the –SH groups and thus, it cannot be

• compared to the theoretically proposed compound. Another alternative would be the use of some chemical agent to break the disulfide bond in 2, but it could induce changes in the conformational isomerism. However, the level of theory (ωB97X-D/aug-cc-pVTZ) used in this work for the studied compounds has

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS₂

• Jing Leng,
• Shi-Meng Wang and
• Hua-Li Qin

Beilstein J. Org. Chem. 2017, 13, 903–909, doi:10.3762/bjoc.13.91

• tetrafluoroborates; carbon disulfide; chemoselectivity; diaryl disulfides; photocatalyst; Findings The development of methods for the functionalization of peptides and proteins under mild conditions is a current frontier in the fields of chemistry, biology and drug discovery [1][2][3][4]. Most of the

• pharmaceutically relevant proteins contain disulfide bonds, furthermore, the disulfide ligation and its established chemoselectivity is of great advantage for proteins’ functionalization [5]. In addition, disulfides also play valuable roles as versatile building blocks for industrial applications [6][7][8]. Thus

• transformations with applications in industry is considered of high practical value. In this context, carbon disulfide, a cheap and abundant chemical, has been widely used as reactant and solvent in both industry and materials science. For example, Batanero and co-workers reported an electrochemical

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

• systematically used as reference when analyzing the modified gold surfaces after the reaction process. Synthesis of sulfamide 1 The disulfide 1 was synthesized following our previous procedure from commercially available 4-aminophenyl disulfide and the readily prepared 4-methyl-N-(tosyloxy)benzenesulfonamide in

• materials science and the results will be reported in due course. Experimental Synthesis of sulfamide 1 Triethylamine (0.75 mmol, 105 µL, 3 equiv) was added to a solution of bis(4-aminophenyl) disulfide (0.25 mmol, 62 mg, 1 equiv) in dichloromethane (1 mL). The solution was cooled down to approximately 10

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -propargylamines and carbon disulfide The first example of a cyclization of N-propargylamines 1 with carbon disulfide to lead to 5-methylenethiazolidine-2-thiones 2 was reported in 1949 by Batty and Weedon. The reaction took place in refluxing ethanol and generally afforded the corresponding products in good

• yields. It was also observed that products 2 rapidly formed by reaction of 1 with carbon disulfide in the presence of sodium hydroxide as the base in water at 20 °C. Further, the authors showed that treatment of methylene compound 2 with cold concentrated sulfuric acid gave the corresponding isomeric

• high yields through a condensation of commercially available and cheap N-propargylamine, allyl bromide, and carbon disulfide [100]. Conclusion Much work has been carried out during the past decade and has demonstrated that N-propargylamines are one of the most useful and versatile precursors in the

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

• 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

• of aryl thiols include the Leukart thiophenol synthesis [86], the Newman–Kart reaction [87][88] and the Schonberg reaction [89]. These methods often require multiple steps and/or harsh conditions. The reduction of phenylsulfonic chloride and disulfide can also afford aryl thiols, but the preparation

• intramolecular sulfide and disulfide compounds, so that it is difficult to isolate aryl thiols as final product. For example, many reactions use aryl thiols as active intermediates to form benzothiazoles from aryl halides [95][96]. The first report of a transition-metal-catalyzed synthesis of aryl thiol appeared

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

• disulfide 12 (Scheme 12), used as food flavour additive [67]. To demonstrate the usefulness of the flow methodology, and its applicability, the photocatalytic aerobic oxidation of a peptide to obtain oxytocin in continuous flow was reported (Scheme 12). Full conversion was achieved in water with 200 s of

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• dichloromethane. After disulfide-bond cleavage with a solution of tris(2-carboxyethyl)phosphine (TCEP) in a 1:5:10 mixture of phosphate-buffered saline (PBS)/chloroform/methanol at pH 7, the filtrate was analyzed by HPLC–MS. As expected the corresponding mass m/z 493.2 [M + H]+ of the cleaved cycloaddition

• was incubated with 2, the disulfide bond was cleaved and the filtrate subsequently analyzed by HPLC–MS. To our surprise, the BPC showed one distinct peak at 8.1 min with a characteristic MS2 fragmentation pattern of a derivatized azide and a mass of m/z 567.2 [M + H]+. This mass corresponds to the

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

• ; for instance, Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide) [1][2][3], Berzelius reagent [4][5][6] (P4S10), and phosphorus pentasulfide [7] in dry toluene, xylene or pyridine under reflux conditions. A two-step approach for the purpose of thiation of

• efficient method for the transformation of heterocyclic amides to heterocyclic thioamides gained great attention. The reaction of three molar equivalents of cyclohexylamine (1) with one molar equivalent of carbon disulfide in water typically afforded N-cyclohexyl dithiocarbamate cyclohexylammonium salt (2

• cyclohexylamine (60 mmol) and water (50 mL) was added carbon disulfide (21 mmol) dropwise. The reaction mixture was stirred at room temperature for 2 h. The white solid obtained was filtered, washed with water, dried and crystalized from ethanol to provide the pure product. Yield 98% (ethanol 95%) white crystals

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• Lewis X trisaccharide: The reaction of 7 with disaccharide 8 promoted by dimethyl disulfide and triflic anhydride gave trisaccharide 9 with high α-selectivity (Scheme 3) [12]. These conditions, using this promoter system, worked fine in a number of similar cases. The less-stable trimethylsilyl group has