Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• to the guest molecules [9][10]. These cyclodextrins linked by ester [11], thioether [12][13][14][15][16], urea [17][18][19], or triazole [20] moieties have been previously described. In addition, aromatic azobenzenes are excellent candidates as molecular switch linkers as they have two forms, namely

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• use of silyl, stannyl and thioether groups is generally preferred, since these groups are typically cleaved off upon anodic oxidation. A number of intramolecular cyclizations of 23- and 24-type intermediates have been reported both in presence and absence of electroauxiliaries. In the course of their

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• reasoning being that these are structurally related to planar chiral ferrocenes [32][33][34] and should thus behave in a similar fashion. To date though, we had not been in a position to examine whether this hypothesis was true. However, with the synthesis of inherently chiral thioether oxazoline

• calixarenes 5–8, we noted their similarity to planar chiral thioether oxazoline ferrocene ligands (9 in Figure 1) already reported by Dai and co-workers [35]. We therefore initiated a pilot study with our inherently chiral calix[4]arenes, using the palladium-catalyzed Tsuji–Trost allylation reaction (Scheme 3

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• (1o) underwent the alkylation/C3–C2 migration sequence to give 2-(methylthio)tryptophan 3o in good yields (Table 3, entry 5). Remarkably, the presence of a thioether in the indole ring offers unique, site-specific handles that can be utilized for further functionalization of the tryptophan moiety

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• heteroaromatic core with the benefit of sulfur chemistry [36]. Sulfur facilitates the synthesis by providing a strong nucleophile and access to a thioether linkage under mild conditions, but it also enhances a number of potentially useful physical properties. For instance, polysulfuration of an aromatic core is

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• orthogonality of these two reactions for the growth of multifuncional dendrimers [22]. Results and Discussion Owing to their straightforward access, their high nucleophilicity and the stability of thioether conjugates, glycosyl thiols [23][24], α-D-ManSH 1 and β-D-GlcNAcSH 2 have been selected for this study

• (Scheme 1). Such derivatives have proved to be useful in bioconjugates chemistry [25] and for the preparation of thioether-linked tetravalent glycocyclopeptides which have shown highest inhibition against a model lectin in comparison with analogues bearing oxime and triazole linkage [26]. Glycosyl thiols

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• conditions the available amount of lactone is below the recognition threshold and therefore scarcely effective as an immunostimulant. Several years ago [31], we reported on the conformational analysis and the synthesis of thioether 3 (Figure 1), a hydrolytically stable mimetic of the GM3-lactone 2

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• modified by fatty acid acylation [97]. The synthesis of these lipidated peptides can be performed by amidation, S- or O-esterification as well as thioether or -sulfide formation. Owing to the strength of the covalent bonds, amidation and O-esterfication are preferred over the other strategies [97

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• methylated β-cyclodextrin (RAMEB-CD). Additionally, the influence of the oxidation of the incorporated thioether linkages on the cloud point is investigated. The resulting hydrophilic sulfoxides show higher cloud point values for the lower critical solution temperature (LCST). A high degree of

• using classical free-radical chain transfer polymerization techniques. These polymers contain oxidation-sensitive thioether linkages. Up to now, to the best of our knowledge, the simultaneous influence of oxidation and cyclodextrin-sensitive end-groups on the solution properties of poly(N,N

• the signals of the backbone between 2.0–3.9 ppm and 0.7–2.0 ppm, respectively (see Figure 2 for polymer 9b and Supporting Information File 1, Figure S6 for 8b). Oxidation of the end-group-functionalized polymers. The selective oxidation of the thioether groups to the corresponding sulfoxides was

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• processes (e.g., Norrish type II reaction) [38][45][46] that produce cyclic amides 5 via 4 (Scheme 2), photoirradiation of phthalimides containing thioether and/or amine chains 2 promotes more rapidly the intramolecular SET from the heteroatom donors (S and N) to the phthalimide excited states. The SET

• solution take place with high efficiencies and regioselectivities to form the respective lariat-type crown ether products 42. In a similar manner, naphthalimides 45a–c containing non-silyl ether and thioether, and silyl-thioether-terminated, N-branched side chains undergo photoreactions to generate the

• to which various kinds of donor functionality can be appended. By employing this approach, a number of lariat-type azacrown ethers including 72–74 which possess aminoether and thioether side chains, have been prepared. Lariat-type crown ether-based fluorescence sensors for heavy metal ions Since the

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• with quantitative conversion to give the 1,4-disubstituted 1,2,3-triazole exclusively. Common side reactions such as the Glaser coupling [9][10][11] are not observed. The presented reaction conditions are compatible with a variety of functional groups such as ester, ether, amide, thioether, Fmoc and

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Topochemical control of the photodimerization of aromatic compounds by γ-cyclodextrin thioethers in aqueous solution

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1858–1866, doi:10.3762/bjoc.9.217

• configuration of the dimeric inclusion complex of the guest. Anti-parallel orientation of acenaphthylene within the CD cavity led to the exclusive formation of the anti photo-dimer in quantitative yield. Parallel orientation of coumarin within the complex of a CD thioether led to the formation of the syn head

• allows for photoreactions even for short-lived excited states. In comparison to other confined and ordered media, most γ-CD thioether complexes offer the advantages of very high quantum yields and excellent stereochemical control. Because the product formation is mainly topochemically controlled

• aqueous solution of the inclusion complex of ACE with γ-CD thioether. Molecular modeling: A previously described procedure was used [25]. The geometries of the orientational isomers of the COU gas-phase dimer were fully optimized without any symmetry restriction at the MP2/6-31G* level of theory by using

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• enantioselectivity of the β-(N-acylamino)aryl thioether (up to 92% ee), with only 1 mol % of chiral guanidine OC-46 as a catalyst. Based on density functional theory (DFT) calculations, a plausible mechanism indicated that the hydrogen-bonding interaction between the chiral guanidine and the carbonyl group in meso-N

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• ) undergoes cyclometalation to form [Pt2(bph)2(μ-SEt2)2] 22 and biphenyl H2bph (Scheme 15) [117]. Intramolecular C–H bond activation seems to be driven by thioether dissociation via 21, a process previously reported for the complex [Pt2(Me)4(μ-SMe2)2] [119]. Marrone et al. computed the cyclometalation process

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests

• Sophie Fourmentin,
• Anca Ciobanu,
• David Landy and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1185–1191, doi:10.3762/bjoc.9.133

• localization of the substituents in position 6. This finding is consistent with previous observations of the high binding potentials of CD thioethers for other guests [32][33][39]. The binding constants of the neutral thioether 3 were in most cases higher than the ones of the anionic thioether 4. The high

• cavity 262 Å3 [41], which means that the β-CD cavity within host 4, extended by the thioether substituents, is nearly completely occupied by it. The ability of the program Macromodel (from Schrödinger Inc.) to predict the nonpolar interactions between host 4 and benzene derivatives was finally evaluated

• ]. The host structure was based on a nondistorted β-CD with C7 symmetry, on which primary hydroxyl groups were replaced by thioether arms (with a linear conformation, leading to a tubular extension of the cavity). Guests were constructed manually and submitted to minimization, prior to inclusion

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• monoamine-monoamide bisthiol protected with p-methoxy benzyl (MAMA-PMB, 87) to give 88 (Scheme 7B) [68]. Nitro reduction of 88 followed by thioether deprotection gave MAMA-BTA (89), which was labeled through reaction with the [Re] (used for in vitro studies) or [99mTc] precursors to give the desired 83a,b

• observed that bulky, hydrophobic thioether substituents (such as R4 = SCH2C6H4-p-OMe) were well tolerated at this position. This finding was of particular interest as it provided a possible means of generating new PET ligands via [11C]- or [18F]-labeling through S-alkylation. The [18F]-labeled

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• (SAR) studies revealed that the thioether and pyridazine moieties were essential molecular components for increasing EAAT2 protein levels [16]. Of the analogues developed, several thiopyridazine derivatives (Figure 4) were found to increase EAAT2 levels greater than six-fold over endogenous levels in

• accumulation, respectively [30]. Metabolic profiling and further chemical modification were performed to increase the stability and potency of ASP derivatives, and this ultimately led to replacement of the thioether with an ether linkage and the identification of a new aryloxanyl pyrazolone (AOP) scaffold

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• thioether such as 1 as an activated alkyne. After a carbocupration of the alkynyl thioether 1 with the organozinc reagent 2 in the presence of CuCN·2LiCl [14], the alkenylcopper species 3 should be obtained. Stereoselective quenching with an electrophile (E1) should afford the tetrasubstituted alkenyl

• thioether 4. Extensive experimentation showed that thioethers 4 do not undergo Ni- or Pd-catalyzed cross couplings leading to products of type 5 (R = Me, Ph) [15][16]. Thus, we designed a new sulfur–lithium exchange (Scheme 1). Sulfur–lithium exchanges proceed only readily with sulfoxides [17][18][19] and

• these reactions are often complicated by radical side reactions [20][21]. This new, direct sulfur–lithium exchange on an alkenyl thioether of type 4 involves the use of a bromobiphenyl R-group, which by treatment with BuLi at low temperatures, undergoes first a fast bromine–lithium exchange leading to

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• led to the fluorenylmethyl-protected thioether 8 in high yield. The suggested mechanism for this reaction comprises the addition of the cysteine thiolate on the exocyclic double bond of dibenzofulvene, which is formed during Fmoc deprotection. The influence of base concentration on this

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1890–1895, doi:10.3762/bjoc.8.218

• , such as thioether moieties, is known to furnish host molecules with much higher binding potentials than native β-CD [46][47]. Conclusion The binding potential of β-CD can be improved significantly if hydrophobic substituents are exclusively attached at the primary positions. Intramolecular hydrogen

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• of C60 in water reaching concentrations of 15 mg/L. Equilibrium state was approached after seven days without the use of organic cosolvents. The 1:2 stoichiometry of the C60/γ-CD thioether complexes was demonstrated by a parabolic phase-solubility diagram. In contrast, native γ-CD forms nanoparticles

• dissolution of C60 by γ-CD thioethers had been demonstrated, we were interested in how long it takes to reach equilibrium, within experimental error. Therefore a thinly casted film of C60 was incubated with an aqueous solution of γ-CD thioether 7 at 50 °C and stirred according to Kuroda et al. [37]. The slow

• Geckeler for other amino compounds [39]. The phase-solubility diagram of C60 in the presence of γ-CD thioether 3, according to the method established by Higuchi and Connors [40], was obtained by plotting the concentration of the dissolved C60 versus the concentration of the host, as depicted in Figure 4

Intramolecular bridges formed by photoswitchable click amino acids

• Christian Hoppmann,
• Ronald Kühne and
• Michael Beyermann

Beilstein J. Org. Chem. 2012, 8, 884–889, doi:10.3762/bjoc.8.100

• the yield of the intramolecular thiol click reaction increased (Figure 2, data shown for peptide 1). At the highest GSH concentration tested (10 mM), only the intermolecular click product 5 ([M + 2H]2+ = 960.90) was detected as the corresponding sulfoxide of the thioether formed in the crosslinked