Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• addition of thiols to alkenes – known as thiol–ene coupling, TEC – a very efficient metal-free click reaction [18][19]. We prepared n-alkyl 1-thio-β--glycosides from unprotected sugar anomeric thiols, commercial n-alkenes and one synthetic lipophilic scaffold presenting two reactive alkenyl ends. Although

• compounds similar to other efficient multivalent glycoconjugates obtained by TEC of sugar thiols with different multivalent scaffolds such as octasilsesquioxanes [35], cyclopeptides [36][37] and polymers [38]. Both compounds 5 and 8 showed low IC50 values (a tenth to some hundreds of micromolars) where the

• were kept as significant. Pictures were prepared using PyMOL (version 0.99rc6, DeLano Scientific, San Carlos, CA, 700). Structure of the β-thiols 1a and 1b and of the commercial alkenes 2a and 2b. Periodic monitoring by 1H NMR (300 MHz, DMF-d7) of the formation of product 8 from a mixture compounds 1b

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• synthesized according to procedure reported by Kuvychko et al. and adapted by our group [27][28][29]. Though, several compounds are known to undergo the penta-substitution reaction with C60Cl6, like amines, thiols or alcohols [30][31][32], it has been observed that primary amines show a high reactivity under

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• reported that 2,6-diazidopurine nucleosides exhibit opposite regioselectivity with aliphatic thiols, which do SNAr reactions at C(2) position of purines [50][51]. Taking this information into account, we performed an SNAr reaction between 2,6-diazidopurine 2a and piperidine and obtained the C(2

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• Orgánica, Facultad de Química, Bioquímica y Farmacia, UNSL. Chacabuco y Pedernera, San Luis, 5700, Argentina 10.3762/bjoc.15.34 Abstract A preparation of β-ketosulfides avoiding the use of thiols is described. The combination of a multicomponent reaction and a lipase-catalysed hydrolysis has been

• ; sulfoxide; thiol-free; Introduction Throughout the years, several strategies have been developed to build up organic compounds bearing a sulfide moiety [1][2]. Often, thiols (or the corresponding thiolate anions) are employed as nucleophilic sulfur reagents in order to react with a suitable electrophile [3

• ][4], however, there are certain negative aspects of thiols that need to be taken into account (i.e., foul smell, easy oxidation into disulfide, participation as donors in one-electron events, reaction with olefins through ene-type reactions, etc) [5][6][7][8]. Hence, the development of thiol-free

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• activity against Candida albicans and Candida tropicalis [8] and 2-mercapto-1,3-benzothiol and its derivatives exhibit inhibitory effects against thyroid peroxidase [9]. (Hetero)aryl thiols are often prepared from the corresponding halides through direct nucleophilic substitution [10][11][12] or metal

• benzoxazoles to the corresponding thiols through direct C–H mercaptalization using 1,3-propanedithiol as thiol source. Results and Discussion Previous studies in our group revealed that small aliphatic diols and dithiols are promising reagents for the synthesis of phenols and arylthiols, respectively [23][37

• groups as well as halogens are well tolerated under the developed reaction conditions. Benzoxazoles were also successfully converted to the corresponding thiols. The relatively lower yields can be attributed to the partial decomposition of benzoxazoles caused by KOH at high temperature. In order to get

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• reported by many researchers [67][68][69]. 3-1. Methyl transfer to thiols Chemical reductants such as NaBH4 or electrochemical reduction could provide Co(I) species, so that α-methylated and β-methylated B12 could be formed by the oxidative addition reaction with a methyl donor. The supernucleophile Co(I

• ) species readily react with various methyl halides such as methyl iodide to form a methyl–cobalt complex. Moreover, methanol could also serve as a methyl donor after the activation of the OH group by a Lewis acid such as Zn2+ [70][71]. Thiols could also mediate the methylation of 1 with methyl iodide or

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• , antidepressant or antileukotriene agents (Figure 1). Three of the five most selling drugs in 2015 were organosulfur compounds. The majority of methods for C–S bond synthesis use transition metal-catalyzed cross coupling of thiols and their derivatives with organohalides [4][5][6], arylboronic acids [7], aryl

• triflates [8], and diazonium salts [9]. Typical metals used are palladium [10][11][12][13], copper [14][15][16][17][18][19][20][21], nickel [22][23][24], iron [25][26][27][28][29], cobalt [30][31][32], and rhodium [33][34]. Aryl sulfides are also synthesized by cross coupling of thiols and aryl Grignard

• prefunctionalized sulfenylating reagents. Recently Lei and co-workers reported a DDQ-mediated selective radical–radical cross coupling between electron-rich arenes and thiols [40]. Miyake et al. reported the visible light-promoted cross-coupling reaction between aryl halides and arylthiols via an intermolecular

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• -250TM, ChemoMetec A/S, Lillerød, Denmark) using Vitabright-48™ (ChemoMetec A/S, Lillerød, Denmark), a cell permeable dye that reacts with thiol groups to form a fluorescent product. An inverse correlation has been shown between the concentration of thiols and progression of apoptosis; the level of

• thiols, and hence the fluorescence intensity of this dye decrease in response to induction of apoptosis [44]. Based on the percentages of apoptotic cells shown in Table 4, there was a good match between the values provided by these two different methods. As expected, the maximum apoptotic effect was

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

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

• structural characteristic of peptides is the disulfide bridge formed by cysteines. This functional group is much more prevalent in peptide medicinal chemistry. Noël et al. have published a protocol for the aerobic oxidation of thiols to disulfides, using Eosin Y photocatalysis and TMEDA (Scheme 3) [43]. The

• reaction specifically investigated the dimerization of thiols. Some of the experiments carried out by the group were in a flow chemistry set up, exemplifying the scalability of the procedure. In addition, the oxidant that achieves the transformation is molecular oxygen, making this a very sustainable route

• , in a similar manner to the amide coupling by Leow. The demonstrated oxidation of the free thiols to a disulfide to afford oxytocin (3c) as the product in quantitative yield shows the value of this procedure. Medicinal chemists who specialise in creating artificial peptides could find much use for

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• . Strong nucleophiles (e.g., primary amines or thiols) react with epoxides more rapidly than do weak nucleophiles (e.g., like primary alcohols). This functionalization approach based on the epoxides’ opening enables the introduction of the reactive groups to the surfaces of graphene-family materials. The

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

• makes them highly susceptible to nucleophilic attack and makes them versatile starting materials for the synthesis of various derivatives [16][17][18]. A number of protocols have been reported to effect their selective ring opening using thiols or disulfides as nucleophiles to obtain β-hydroxy sulfides

• . 3.1.1 Thiols as nucleophiles. Thiols, in the presence of a wide variety of catalysts, yield sulfides upon opening of epoxides under a variety of reaction conditions and these have been comprehensively reviewed [19]. More catalysts and reaction conditions, novel or modern variations of the old, keep

• thiols to give various β-hydroxy sulfides in good yields (Scheme 1) [20]. Both aryl and alkylthiols were found to be capable of opening the epoxide ring under the reaction conditions, and with respect to the epoxides, cycloalkane, alkene and 1-substituted alkene oxides were all amenable to the reaction

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• , some other NH acids, and thiols. The standard azo reagents used are diethyl- (DEAD) or diisopropyl- (DIAD) azodicarboxylate. However, alternative reagents such as azodicarboxamides [15][16] or stabilized phosphoranes were also developed to allow reaction with nucleophiles of weaker acidity. The typical

• with trifluoroethanol, having a pKa of 12.4 (Scheme 19) [77]. The efficiency of the Mitsunobu glycosylation with fluorinated alcohols with pKa values between 9 and 12 was demonstrated with several other examples [78]. Also thiols, according to their pKa value range between 10 and 11 should be qualified

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• efficiency of the reaction is limited by the need to use 2 equivalents of allenes 20 to obtain good yields. λ3-Iodane reagents: alkynylbenziodoxolone Ethynylbenziodoxolone (EBX) is a powerful reagent to perform the electrophilic alkynylation of various functional groups such as carbonyl derivatives, thiols

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

• anticancer drug due to its improved cytotoxicity/myelotoxicity ratio [47][48]. Brostacillin acts as an effective DNA alkylator only in presence of high levels of cellular thiols such as glutathione [49]. Moreover, it was thirty-fold more active in comparison to TAM in inducing apoptosis in A2780 human

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• biological investigation of 3 in this direction. From the view point of organic synthesis, the newly synthesized ortho-SF5-substituted unsymmetrical iodonium salts 3p, 4b, 5a and 6a have potential use as electrophilic SF5-phenylation reagents for a range of nucleophiles such as alcohols, amines, thiols, and

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

• . General concepts, synthetic strategies and the substrate scope of reactions yielding thiols, disulfides, sulfoxides, sulfones and other organosulfur compounds are discussed together with the proposed mechanistic pathways. Keywords: disulfides; photocatalysis; sulfones; sulfoxides; thiols; visible light

• over the most important visible-light induced and photoredox-catalyzed approaches for the formation of C–S bonds (Scheme 1). The survey is structured according to the sulfur-containing starting material, beginning with sulfur at its lowest oxidation state – and covers: Thiols, thiocyanates, carbon

• radical initiators as well as photocatalytic reactions, where sulfur-containing substrates act as a sacrificial agent are not discussed in this review [23][24][25][26][27][28]. Review Thiols Formation of sulfides and sulfoxides A large number of photocatalytic C–S bond-forming methods report the

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

• synthesized in two steps (Scheme 5). Herein, the treatment of methyl-terminated triethylene glycol monolayer-protected AuNPs (Me-EG3-AuNPs) with ω-carboxy tetraethylene glycol thiols (HOOC-EG4-SH) gave carboxy-functionalized AuNPs (HOOC-EG4-AuNPs). Peptide coupling of these HOOC-EG4-AuNPs with a DBCO-amine

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• thiols do not add to 3, but in the presence of triethylamine ring opening again takes place [18]. Further chemistry of the ketenes obtained by FVP of 5-tert-butyl-4-pivaloylfurandione (6) and 5-tert-butyl-4-methoxyfurandione and their dimers has been reported [20]. It is worth noting that the bisdioxines

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

• derivatives. Morevover, the scope could be extended to other substrates of interest, such as activated benzene derivatives and thiols. Similarly, Lu, Zhao and co-workers found out that excellent yields could also be achieved for indole derivatives when replacing PMe3 or (EtO)2P(O)H by cheap and stable

• permitted to perform the trifluoromethylsulfenylation of thiophenol derivatives at room temperature (Scheme 36) [45]. These conditions proved to be tolerant with variously substituted aryl thiols, but no conversion was observed for any aliphatic substrates. 3 Trifluoromethylsulfinylation Following a similar

• )arenes and thiols. PPh3/NaI-mediated trifluoromethylsulfenylation of indole derivatives. PPh3/n-Bu4NI mediated trifluoromethylsulfenylation of thiophenol derivatives. PPh3/Et3N mediated trifluoromethylsulfinylation of benzylamine. PCy3-mediated trifluoromethylsulfinylation of azaarenes, amines and

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

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

• , such as 1,2-diamines and β-aminoalcohols are of special importance as they offer access to a variety of heterocycles through an addition–elimination–heterocyclization sequence. Their ability to act as single-electron acceptors, demonstrated in the reaction with thiols and selenols, allows their

• ). Formation of disulfides through reaction of thiols with E-1a. Formation of CT salts of E-1 with Mn2+ and Cr2+ metallocenes through one-electron transfer. Oxidation of diethyl dicyanofumarate (E-1a) with H2O2 to give oxirane 101. The aziridination of E-1b through nitrene addition. Acknowledgements The

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• transition metals, could be performed in shorter reaction time and uses stable dichalcogenides rather than toxic thiols and selenols. Organometallic synthesis and catalytic application Mechano-synthesis of organometallic compounds The last decade has witnessed a rapid growth of mechanochemistry in organic

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

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

• , Jadavpur, Kolkata 700032, India. Fax: +91 33 24730957; Tel: +91 33 23223403 10.3762/bjoc.13.174 Abstract The present work demonstrates the C–S cross-coupling reaction between aryl halides and thiols using nickel nanoparticles (Ni NPs) supported on reduced graphene oxide (Ni/RGO) as a heterogeneous

• first palladium-catalyzed arylation of thiols was reported by Migita and co-workers in 1980 [5], and soon after Cristau and co-workers developed a nickel-catalyzed route for C–S cross-coupling reactions [6]. Other metals such as copper [7], cobalt [8], iron [9], rhodium [10], manganese [11], indium [12

• formic acid at room temperature [48]. Also, it can serve as an excellent catalyst for the Kumada–Corriu C–C cross-coupling reaction [49]. Since heterogeneous Ni catalysts are rarely studied for the C–S cross-coupling reaction between aryl halides and thiols, presumably because of the fact that the thiols