Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• interference has also been described [24]. We recently reported the synthesis of a number of chiral disulfide sulfurizing reagents [25] and the results of the sulfurization of phosphite triesters in order to look for stereoselectivity [26]. In order to change such a method into a practical synthesis route for

• 16. Treatment of 16 with approximately 4 equiv of phenylacetyl disulfide (PADS) [57] gave the known dinucleoside phosphorothioate 17 [26][58]. Phosphorus epimerization. During the many attempts to purify the acyl dinucleosides by chromatography, it became apparent that some fractionation of the

Synthesis of a resin monomer-soluble polyrotaxane crosslinker containing cleavable end groups

• Ji-Hun Seo,
• Shino Nakagawa,
• Koichiro Hirata and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2014, 10, 2623–2629, doi:10.3762/bjoc.10.274

• (PRX) crosslinker with cleavable end groups was synthesized to develop degradable photosetting composite resins. The PRX containing 50 α-cyclodextrins (α-CDs) with disulfide end groups was initially modified with n-butylamine to obtain a resin monomer-soluble PRX. The PRX containing 13 n-butyl groups

• -soluble PRX crosslinker can be applied to design degradable photosetting plastics potentially used in the industrial or biomedical field. Keywords: α-cyclodextrin; composite resin; disulfide; polyrotaxane; Vickers hardness; Introduction Polyrotaxane (PRX) is a supermolecule containing host molecules

• ][4]. For example, if cleavable end-capping groups such as disulfide groups are introduced at both ends of PRX, the threaded α-CD molecules could be completely released by disassembling the PRX structure when a preferable stimulation such as dithiothreitol (DTT) is applied to the cleavable end-capping

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• ][45][46][47][48]. The amino-alkylthiol linker is introduced as its disulfide dimer to protect the sulfur and ensure that the reaction with the convertible nucleobase occurs via the amino group. Two of these residues are placed in adjacent base pairs and reduction of the linker disulfides frees the

• thiol groups, which, upon removal of reducing agent, react under oxidative conditions to form a disulfide cross-link. Adjacent A/A, C/C, G/G and T/T cross-links have been synthesized with this method. An interstrand G/G cross-link of adjacent G/C base pairs was used to study binding of the DNA cytosine

• thionucleosides like 2’-deoxy-6-thioinosine (dI6S) with 2’-deoxy-4-thiothymidine (dT4S) or 2’-deoxy-4-thiouridine (dU4S) via a disulfide linkage, appears to be very attractive for studying protein–DNA interactions. These thionucleosides can easily be incorporated in synthetic ODN and the linkage is formed without

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• based on an asymmetric sulfuration (route A) or asymmetric alkylation (route B) of a chiral phosphorus carbanion (Scheme 12) [36]. Deprotonation of (R,R)-28a and alkylation with 3-(3’-phenoxyphenyl)propyl iodide (96) gave 97. Sulfuration of the Li anion of 97 with tetramethylthiuram disulfide provided

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

• previous route, we expected that the presence of unreacted sugar 2 (used in slight excess) might not interfere during the thiol–ene coupling as it should form disulfide adduct spontaneously. Therefore, the crude mixture was neutralized by addition of hydrochloric acid and compound 6 was used without

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• propylpyridine (6). In the bouquet of the headspace extract of Streptomyces strain FORM5 several other compounds besides the pyridines 6–12 were identified (Figure 7, Table 1). The most abundant of these were dimethyl disulfide (35), accompanied by other sulfur components as dimethyl trisulfide (36), dimethyl

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• . Ozone was passed through a cooled solution of 11 (51 mg, 0.023 mmol) in CH2Cl2 (10 mL) until the blue color persisted (10 min). Dimethyl disulfide (210 μL) was added, the mixture was stirred for 10 min, concentrated, and the residue was dissolved in methanol (10 mL). Sodium borohydride (40 mg) was added

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• that a release mechanism of the cytotoxin is part of the molecular architecture of the conjugate [31]. Disulfide linkers have shown to be well suited when utilizing the reducing power between extra- and intracellular milieus which results in cleavage and liberation of the drug. Mitomycin conjugates [32

• ] were one of the earliest examples of folate disulfide–drug conjugates and after the conjugate is internalized by endocytosis, it was demonstrated that the endosomes exert reductive cleavage. For conjugate 7 we found that disulfide cleavage provided a thiol derivative of ansamitocin P-3 (4, AP-3) 8 with

• order to broaden the opportunities of this approach for the ansamitocins, we now describe alternative accesses towards disulfide linked conjugates that are based on thiol-functionalized AP-3 derivatives. These are planned to be obtained by a combined muta- and semisynthetic strategy using different

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• second [37] reported crystal structure of a cis-cylcodiphosphazane-2,4-disulfide with aromatic substituents on nitrogen. For all other known structures of this type the configuration is either not specified or trans. Since generating and separating mixtures of cis/trans-isomers is undesirable we

• literature hitherto [47]. Preparation of cis-2,4-bis(((R,R)-2-(dimethylamino)cyclohexyl)amino)-1,3-diphenylcyclodiphosphazane-2,4-disulfide (14a): To a stirred solution of (R,R)-N1,N1-dimethylcyclohexane-1,2-diamine (400 mg, 2.81 mmol) in DCM (4 mL) was added a solution of 2,4-dichloro-1,3

• -diphenylcyclodiphosphazane-2,4-disulfide (532 mg, 1.40 mmol) in DCM (2 mL) via syringe at 0 °C. After 0.5 h, Et3N (284 mg, 2.81 mmol) was added via syringe and the mixture was kept stirring at 0 °C for further 0.5 h. The reaction was allowed to warm to rt and stirred for 1 h at this temperature. The solvent was removed in

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

• Samir Kundu,
• Babli Roy and
• Basudeb Basu

Beilstein J. Org. Chem. 2014, 10, 26–33, doi:10.3762/bjoc.10.5

• showed varying results under conditions A or B, and allyl acetate did not undergo any desired reaction, but merely produced the disulfide from oxidative dimerization of the thiol (Table 1, entries 6–8). Allyl tosylate, however, produced the desired thioethers in a regioselective manner, but with

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

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

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

• generation of carbamodithioic acids from amine and carbon disulfide is also investigated to provide ring-opened products 76 to 80 in high yields and good enantioselectivities (Scheme 11). Chiral 1,2,3-triazolium chlorides Most recently, Ooi [52] and colleagues have described a desymmetrization of meso-N-p

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• fragmentation of 5-ring spiroketal 1 cannot be excluded. It is known that the sulfur analogue 4,7-dihydro-1,3-dithiepine-2-yldidene cleanly fragments into carbon disulfide and butadiene [32]; however, 4,7-dihydro-1,3-dioxepine-2-ylidene does not give carbon dioxide and butadiene [33]. Conclusion In agreement

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• polycationic system was synthesized via copolymerization of N,N-diethylacrylamide (DEAAm) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). N,N’-bis(4-chlorobutanoyl)cystamine was used as disulfide-containing cross-linker to form networks by the quaternization of tertiary amine groups. The insoluble cationic

• hydrogels become soluble by reduction of disulfide to mercaptanes by use of dithiothreitol (DTT), tris(2-carboxyethyl)phosphine (TCEP) or cysteamine, respectively. The soluble polymeric system can be cross-linked again by using oxygen or hydrogen peroxide under basic conditions. The redox-responsive polymer

• transition temperature (Tg), swelling behavior and cloud points (Tc) were investigated. Redox-responsive behavior was further analyzed by rheological measurements. Keywords: cationic hydrogel; cross-linked polymer; 2-(dimethylamino)ethyl methacrylate (DMAEMA); disulfide cleavage; N,N-diethylacrylamide

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• isocyanides [30][31], guanidines [32][33] and thiosemicarbazides [34]. Due to the limited commercial availability of diversely functionalised isothiocyanates chemists normally pursue a de novo synthesis, which most commonly involves the condensation of an amine with thiophosgene or carbon disulfide [35][36

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• ). Oxidative addition of the disulfide byproduct to the initial product furnishes a pentavalent phosphorus species that is eventually hydrolyzed to an S,S-diphenyl dithiophosphonate upon workup. Barton also reported that white phosphorus reacts with N-acyloxythiopyridones, so-called Barton PTOC esters (Scheme

Photoinduced synthesis of unsymmetrical diaryl selenides from triarylbismuthines and diaryl diselenides

• Yohsuke Kobiki,
• Shin-ichi Kawaguchi,
• Takashi Ohe and
• Akiya Ogawa

Beilstein J. Org. Chem. 2013, 9, 1141–1147, doi:10.3762/bjoc.9.127

• excess amounts of either starting substrate were employed, the yields of 3aa increased (Table 3, entries 1, 2 and 5). In the case of the reaction of triphenylbismuthine with diphenyl disulfide (4) instead of diphenyl diselenide, diphenyl sulfide 5 was obtained in lower yield with unidentified byproducts

• yield of 3, and the use of diphenyl disulfide (4), which has a lower carbon-radical-capturing ability than diselenide, decreased the yield of 5. (The exact capturing abilities of diselenide and disulfide toward the phenyl radical are not known, but they have been reported toward vinyl radicals, where

• diselenide has a higher capturing ability than disulfide: kSe/kS = 160 [57][58][59].) These facts also support that the reaction starts from the generation of an aryl radical. On the other hand, a pale yellow solid, insoluble in organic solvents, was obtained as a byproduct after the reaction. We assume that

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• by solid-phase microextraction (SPME) and by CLSA. The obtained headspace extracts were subsequently analyzed by GC–MS, leading to the identification of the volatiles dimethyl disulfide (1), dimethyl trisulfide (2), S-methyl methanethiosulfonate (3), dimethyl telluride (4), dimethyl telluryl sulfide

• pathways, as a dmd-gene cluster for the demethylation pathway is located on a 262 kb plasmid and a gene for the lyase DddP is encoded on its chromosome. Isotopically labeled [2H6]DMSP was efficiently incorporated into methanethiol-derived sulfur volatiles like dimethyl disulfide (1), dimethyl trisulfide (2

• including dimethyl diselenide (20) and dimethyl triselenide (21). In addition, the mixed sulfur/selenium compounds dimethylselenyl sulfide (15), bis(methylthio) selenide (16), methylseleno disulfide (17), methyl methylthio diselenide (18), and bis(methylseleno) sulfide (19) were found. A similar headspace

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• thiolate anion by the addition of 2 equiv of KOt-Bu. Different chemical transformations are possible from the arene thiolate ions formed; for example, oxidation to the diaryl disulfide, subsequent nucleophilic substitution reaction with alkyl halides to afford alkyl aryl sulfides, or a second copper

• -catalyzed reaction with a different aryl iodide to yield asymmetric diaryl sulfides. With this strategy we synthesized different sulfur compounds. Accordingly, a solution of benzene thiolate obtained from this methodology affords bis(phenyl)disulfide (51%) after oxidation by KI/I2, by subsequent

New simple synthesis of ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thiones: Direct formation from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles

• Qiuping Ding,
• Yuqing Lin,
• Guangni Ding,
• Fumin Liao,
• Xiaoyan Sang and
• Yi-Yuan Peng

Beilstein J. Org. Chem. 2013, 9, 460–466, doi:10.3762/bjoc.9.49

• and efficient method to construct ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thione derivatives has been developed from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles under mild conditions, without the need for a metal catalyst. The newly developed method

• tolerates a wide range of substrates in moderate to excellent yields. Moreover, this method is advantageous over previous ones for the easy synthesis of reactants. Keywords: 4H-3,1-benzothiazine-2-thione; carbon disulfide; (E)-3-(2-aminoaryl)acrylate; (E)-3-(2-aminoaryl)acrylonitrile; Michael addition

• efficient method to construct ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thione derivatives. In the context of this method, carbon disulfide reacted with (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles under metal-free conditions at room temperature. The newly developed method tolerates a

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• represents the first example of a disulfide and oxime containing metabolite isolated from a marine sponge. Since its initial report by Crews and co-workers as a potent HDAC inhibitor [16], psammaplin A has provided inspiration for the development of new HDAC inhibitors with novel structures [19]. Recently

• unambiguously demonstrated that, similarly to the natural product and clinically approved romidepsin, psammaplin A is a prodrug, requiring reduction of its disulfide functionality to the corresponding thiol monomer 4 (X = OH), in order to potently inhibit HDACs (Scheme 1, right). The resulting thiol moiety acts

• in cell-based assays against A549 (human lung carcinoma), MCF7 (human breast carcinoma) and WI38 (normal human lung fibroblast) cell lines. We attributed this to the low permeability and/or stability of the free thiol in cells. While the use of nonreduced disulfide functionality (e.g., present in the

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

• wish to report the synthesis of the alkynyl biphenyl thioether 1a required for the carbometalation step. Thus, octyne was deprotonated with butyllithium (1.1 equiv, THF, −78 °C, 2 h) followed by the addition of the diaryl disulfide [23] (8: 1.1 equiv, −78 °C to 25 °C, 3 h) providing the bromothioether

• starting from 2,2’-dibromobiphenyl. Thus, the performance of a double bromine–lithium exchange with BuLi (1.1 equiv, −78 °C, 0.25 h) followed by a quenching with tetramethylthiuram disulfide (1.1 equiv, −78 to 25 °C, 12 h) furnishes the dithiocarbamate 13 in 82% yield. Since the reduction to the free thiol

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

• (TES) as cation scavenger [12] yields the O-acetylated glycoamino acid derivative 6 together with its respective disulfide (not shown in Scheme 2), and de-O-acetylation under Zemplén conditions [13] furnishes the unprotected compound 3-dimer after oxidation in air, as reported previously [3]. However

• glycoamino acid derivative 9 was possible by using 50% piperidine in DMF at room temperature to yield the fully deprotected disulfide 3-dimer in 70% yield (Table 1). Separately, 7 was treated with different concentrations of piperidine. When 0.1 equiv of piperidine in DMF was employed, only about 20% of the

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• disulfide-containing linkers, which would be reduced inside the cell so as to release a defined thiol derivative of phalloidin (Table 1). Actin binding All phalloidin derivatives were tested for their affinity to muscle actin (α-actin), which is used as a model for β-actin present in nonmuscle cells. This

• contained a disulfide bridge, arguing for the presence of a disulfide-reducing compartment inside the cells. Likewise, high cytotoxicity was found for the octarginine conjugate (Figure 4a). From the fact that the cytotoxic activities of the polylysine derivative (ca. 150 residues) and the oligoarginine

• with the drug should contain a disulfide bridge, as in compound (2i), to make sure that after internalization the drug is released in a defined and active form. Likewise new, is the observation that the red fluorescent tetramethylrhodaminyl residue can facilitate internalization, e.g., of phalloidin