Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• , 420013, Porto, Portugal Bioprospectum, Lda, UPTEC, 4200135, Porto, Portugal Campus de Ceilândia, Universidade de Brasília, Centro Metropolitano, 72220-275, Ceilândia Sul, Ceilândia, DF, Brazil 10.3762/bjoc.15.247 Abstract Eight new sulfide-based cyclic peptidomimetic analogues of solonamides A and B

• structurally related to these natural peptidomimetics has been used as a promising strategy for the attenuation of bacterial virulence in strains of S. aureus [12][13][14][15]. Herein, we report the synthesis of new sulfide-based cyclic peptidomimetics through the allylic nucleophilic substitution (SN2’) of

• was based on the conservation of the 16-membered macrocyclic scaffold and the apolar tripeptidyl moiety found in the solonamides. Both features are important to guarantee the interference with S. aureus QS [12][13][14][15]. The ester linkage of the lactone core was substituted by the sulfide group

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• (III) chloride in methanol in 88% yield (Scheme 1). The synthesis of allylic alcohol 11, a regioisomer of 6, started again from (1R)-α-pinene (1, Scheme 2). Hydroboration of (1R)-α-pinene with borane–dimethyl sulfide adduct (BMS) and crystallization of the product diisopinocampheylborane (dIpc2BH, 84

• % yield. The allylic diphenylphosphine oxide 21 was subjected to the hydroboration–oxidation reaction introducing stereoselectively the hydroxy group. Hydroboration was carried out with an excess of borane–dimethyl sulfide adduct followed by the oxidation step. The standard C–B bond oxidation protocol

• borane–dimethyl sulfide adduct in THF at 50 ºC. Oxidation of the alkylborane with mCPBA gave the desired alcohol 27 in 51% overall yield. Finally, diastereomeric endocyclic allylic alcohols 16 and 18 were treated with chlorodiphenylphosphine in the presence of DMAP to produce diphenylphosphinites 28 and

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• hexafluorophosphoric acid (Scheme 1a and 1b) [3][4][9][10], oxidation of thioxanthene in the presence of PbO2 followed by dehydration by tetrafluoroboric acid [1], the reaction of 4,4’-bis(dimethylamino)diphenylmethane with sulfur in the presence of ZnCl2 [11], and the ring-closure reaction of diaryl sulfide in the

• ) sulfide (1a) with benzoyl chloride (2a) in the presence of Brønsted acids in chlorobenzene at several temperatures (Table 1). When we used a strong Brønsted acid such as trifluoromethanesulfonic acid (TfOH) at room temperature, the desired thioxanthylium salt 3a was obtained with 21% yield while other

• sulfide 1 and benzoyl chloride 2 (Figure 1). o-Toluoyl chloride smoothly afforded the desired product 3b in excellent yield. Moreover, the reaction was performed on the 2 mmol scale to furnish the desired product in 73% yield, suggesting that the reaction can be applied to large scale conditions. In

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• alcohols and asymmetric sulfide oxidation [91]. Diverse reactivity, cost efficiency and variable oxidation state [Ni(0)–Ni(IV)] associated with nickel led to remarkable developments in the field of catalytic applications [68]. Nickel catalysis involved cycloaddition, cyclization, C–H bond functionalization

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• base, no reaction occurred, and consequenctly the base was necessary for both steps of the thiocarbamate formation. This also explains why two equivalents of base were required. Sodium sulfide as the base provided only traces of 3a suggesting that the activation of sulfur by NaH produces rather a

• polysulfide anion instead of sodium sulfide [74][107][108] (Scheme 7, reaction 3). It caught our attention that only isothiocyanate was generated in the presence of NaOEt (Table 1, entry 20). We suspected that THF might not be the best solvent for this base, hence the reaction was performed in MeCN providing

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• the synthesis of dithienothiophene 1, which is mostly built up by oxidative dehydrocoupling of 3,3’-dithienyl sulfide or ring-closure reactions of brominated thiophenes with ethyl mercaptoacetate, are described in literature [24]. For comparability to the selenophene-containing triacenes 2–4, we

• reinvestigated the synthesis of DTT 1 by using a Cu-catalyzed C–S cross-coupling reaction with potassium sulfide (K2S) as sulfur source [29]. The best results for this C–S ring-closure reaction were achieved by reacting 3,3’-diiodo-2,2’-bithiophene (5) [30] with the system K2S and copper iodide (CuI) as catalyst

• corresponding dibromobiselenophene and benzene sulfonyl sulfide as sulfur source (50% yield) [27]. In parallel, TMS-protected iodinated biselenophene 11 was subjected to selenourea, copper oxide nanoparticles, and potassium hydroxide in DMSO to isolate diselenolo[3,2-b:2’,3’-d]selenophene (DSS, 4) in 48% yield

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• cleavage or oxidation of one sulfide in further studies. Conclusion The reported reaction of [1.1.1]propellane with aromatic and to a certain extend aliphatic disulfides provides access to [2]staffanes and symmetrical and unsymmetrical BCPs. The separation of these compounds is often challenging due to the

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• the solvent for toluene, dichloromethane, dimethylformamide or DMF/H2O (4:1) led to lower yields of the desired aryl cyclopropyl sulfide 1a (Table 1, entry 5) while decreasing the temperature to 50 °C almost completely shut down the reaction (Table 1, entry 6). 1,10-Phenanthroline was found to be the

• , respectively, with no obsevable traces of the desired S-cyclopropylated product 1a (Table 1, entries 11 and 12). Interestingly, however, potassium cyclopropyl trifluoroborate (29) provided the desired aryl cyclopropyl sulfide 1a in 23% yield, albeit with 30% of the diaryl disulfide side-product 26a (Table 1

• (II) acetate, 0.1 equivalents of 1,10-phenanthroline, 2.0 equivalents of potassium carbonate under oxygen atmosphere at 70 °C for 20 hours in a 3:1 mixture of toluene and water afforded the aryl cyclopropyl sulfide 1a in 38% along with 8% of the corresponding side-product 26a and 24% of recovered

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• with the nucleophilic aromatic ring in a Friedel–Crafts alkylation process, thus incorporating the carbon atom in a formal C(sp2)–H/C(sp3)–H cross-dehydrogenative coupling. Finally, an oxidation of sulfide 7 to sulfoxide 8 and the subsequent attack of amide 2 with cleavage of the C–S bond and formation

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• route to 2-deoxyhepuloses 3, 5 and 7 [27][28][29][30]. The hydroboration of enol ethers 2, 4, and 6 with borane dimethyl sulfide in THF, followed by oxidation using hydrogen peroxide and sodium hydroxide gave 2-deoxygalactoheptulose 3 and 2-deoxymannoheptulose 5 in good yields (89% and 78%) and with

• -galactoheptulose (3): Compound 2 (3.66 g, 6.82 mmol) was dissolved in dry tetrahydrofuran (130 mL) under nitrogen and cooled to 0 °C. Borane dimethyl sulfide complex in dry tetrahydrofuran (4.78 mL, 9.55 mmol, 2 M) was added slowly, and the reaction was kept at 0 °C for 2 h. The reaction mixture went from light

• yellow to colorless during the addition of the borane dimethyl sulfide complex. Upon complete consumption of 2, distilled water (15 mL) was added to the reaction mixture slowly (dropwise at first) while vigorous gas evolution was observed. After completion of the gas evolution, sodium hydroxide (14 mL

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• to that for 1 and 2 [37]. Asymmetric reduction of the carbonyl group of 2’-bromobenzophenone (a) with borane dimethyl sulfide in the presence of (S)-(−)-2-methyl-CBS-oxazaborolidine catalyst gave (S)-(2-bromophenyl)(phenyl)methanol (S)-b in 93% yield and 94% ee (Scheme 2 and Figure S1 in Supporting

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• be the optimum leaving group by thorough investigations on the elimination of sulfide, sulfinyl, and sulfonyl groups at the 2-position of benzothiopyranone. Most 2-aminobenzothiopyranones were obtained in good to excellent yields under refluxing in isopropanol within 36 h. This method is base-free

• substituent leading to 2-methylamino-3-cyanobenzothiopyranones was disclosed by Rudorf and co-workers (method C, Scheme 1) [9]. Recently, a similar strategy was successfully utilized to afford N-substituted 2-aminobenzothiopyranones through the replacement of sulfide, sulfinyl or sulfonyl groups with amines

• -imidazolylbenzothiopyranones [10]. It is well known that the sulfide, sulfinyl and sulfonyl groups are generally used as the leaving group for the synthesis of 2-substituted 4H-chromen-4-ones [11][12][13][14][15][16][17][18][19][20][21][22]. Due to the higher electronegativity of the oxygen atom compared to the sulfur atom

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• allyl-sulfide on the surface of the protein. Cross metathesis of the modified protein 82 with allyl alcohol gave the CM product with over 90% conversion (Scheme 18). To achieve this challenging reaction, 200 equivalents (equiv) of HG-II catalyst were employed in a reaction mixture containing 0.01 mM 82

• for the cross metathesis of the allyl-sulfide 99 with allyl alcohol, yielding 50% of product 100 in aqueous mixture (40% t-BuOH) in the presence of 4000 equiv of Mg2+ (Scheme 20). In another recent study, Touissant et al. described the synthesis of two metathesis-based fluorescent probes suitable for

• -metathesis reaction of allyl sulfide 99. Preparation of BODIPY-containing profluorescent probes 102 and 104. Metathesis-based ethylene detection in live cells. First example of stapled peptides via olefin metathesis. RCM of challenging substrate 17 in air and in the presence of water. RCM of N,N

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

• ; 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

• temperature one-pot two-step preparation of the phenacyl allyl sulfide 2h. cIsolated yield. Selective oxidation of the β-ketosulfide 2a. Screening of hydrolases and conditions towards a model substrate.a Lipase-catalysed hydrolysis–protonation sequence over a series of β-thioalkyl enol esters.a Supporting

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• (0.5 mol % relative to the vinylsilyl group, Scheme 3) [9]. Effective cross metathesis was observed when OVS was treated with vinyl sulfide in the presence of second generation Grubbs’ catalyst (Ru-2). The product was obtained in 91% isolated yield, however, the process required a temperature elevation

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• which leads to the formation of methylidene-ruthenium species Ru-A (Scheme 4). Once complex Ru-A is formed, it is prone to be attacked by the electron-rich sulfide ligand positioned opposite to the NHC ligand (trans-influence). This 1,2-sulfide shift generates a new ruthenium complex Ru-B which is

• probably catalytically inactive. This assumption is supported by the isolation of ruthenium complex Ru-13 which was formed by nucleophilic attack of a sulfide ligand onto the electron-poor benzylidene ligand [4]. Hoveyda reasoned that replacing the thiocatecholate ligand (Ru-2) by an electron-deficient

• dichloro catecholthiolate (Ru-3) should render the sulfide ligand less nucleophilic and therefore less prone for nucleophilic attack. This hypothesis gained credence by increased isolated yield for the cross metathesis of allylbenzene with cis-butenediol: Ru-2 (42% yield) versus Ru-3 (61%) yield (Scheme 2c

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• post-expressional protein modifications [10][11][12]. For example, a single cysteine mutant of subtilisin from Bacilus lentus (SBL-S156C) was modified via sulfide bond formation with allyl cysteine displaying an allyl function on the protein surface. This allyl group was modified with a GH-type

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• ). First, we examined the Pummerer reactions in the presence of p-methoxybenzenethiol or p-chlorobenzenethiol; however, the reactions yielded the reductive sulfide 4a. We next examined the stepwise process: i) the Pummerer reaction of 5a with TFAA, followed by ii) the usual work-up and successive treatment

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

• photocatalyst and complete the catalytic cycle forming the sulfate dianion 5 and sulfate radical anion 6. The phenyl sulfide radical 2 formed upon homolytic cleavage of diphenyl disulfide adds to the radical cation of the arene to form the unstable cationic intermediate 3. Aromatization by deprotonation leads

• obtained from the difference spectrum [Ir] and [Ir] + TMB and represents the transient absorption spectrum of 1,3,5-TMB•+ with λmax of 473 nm (solution A). Synthetic routes to organosulfur compounds. Aryl sulfide synthesis. Substrate scope for arylthiol syntheses. The reaction was performed with 1a–g (0.1

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

• since sulfur, in the form of the sulfate ion, is the second most abundant anion in sea water after chloride. As part of natural products, sulfur can appear in a multitude of combinations and oxidation states: thiol, sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal

• , sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal, hemithioacetal, various thioesters, thiocarbamate and isothiocyanate [3]. The three simplest sulfur-containing natural products are perhaps, (E)-2-butene-1-thiol (1), the principal ingredient of the repulsively malodorous

• . The pteriatoxins such as pteriatoxin A (7), were isolated from a Japanese shellfish by Uemura and co-workers in 2001 and proved to be extremely potent neurotoxins in mice [10]. Leukotrienes, which are a family of eicosanoids that are produced in leukocytes, also contain β-hydroxy sulfide moieties, as

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• in the case of 2’-deoxy-4’-thionucleosides [25][26]. When synthesizing 4’-thionucleosides by the way of a sulfide derivative 31, the known chemistry should lead us to use a classical Pummerer reaction to produce 1-acetoxy derivative 33 after converting 31 to the corresponding sulfoxide 32. Even

• ’-thionucleoside derivatives by other groups and became a standard approach for the glycosylation [33][34][35][36][37]. On the other hand, the conversion from the sulfide to 4’-thionucleoside using the Pummerer-type glycosylation included an oxidation step. If the oxidation of sulfide 31 and the Pummerer-type

• thietane nucleosides [47]. The substrate of the coupling reaction was prepared as shown in Scheme 6 starting from benzyloxyacetaldehyde (50). When a hypervalent iodine reagent was used for glycosylation with a diastereomeric mixture of sulfide 53, the reaction stereoselectively gave the ring-expanded

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

• substituted acrylamidines 35 (Scheme 19). The proposed reaction mechanism starts with the activation of DMSO (A) via the iodine(III) species 20b. Iodosoarene C is released under basic conditions, forming the sulfonium intermediate D. This intermediate reacts with the amidine 34 to give the sulfide E, which is

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

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• ) triethyl phosphonoacetate, NaH, DCM; b) TMSN3, Pd(PPh3)4, EtOH; c) i) DOWEX H+, MeOH; ii) O3, dimethyl sulfide, DCM/MeOH; iii) Ac2O, DMAP, pyridine; d) H2, Pd/C, Ac2O; e) MeOH/H2O/Et3N (10:10:1). Proposed mechanism of the Pd-catalyzed azide substitution of 6a in protic solvent. Approach towards

• peracetylated D-IdoNAc 2c, reactions and conditions: a) Ti(OiPr)4, t-BuOOH, D-DET, DCM; b) i) (COCl)2, DMSO, Et3N, DCM, ii) triethyl phosphonoacetate, NaH, DCM; c) TMSN3, Pd(PPh3)4, EtOH; d) i) DOWEX H+, MeOH; ii) O3, dimethyl sulfide, DCM/MeOH; iii) Ac2O, DMAP, pyridine; e) H2, Pd/C, Ac2O. Supporting