Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• cycloisomerization of the α-ketoester 22, which can be described as a Friedel–Crafts-type reaction or an aldol reaction of an S,O-ketene acetal (Scheme 4). The required ketoester 22 was synthesized from sulfonylchromenone 20, accessible from dihydroxyacetophenone 19 and thiol 18 derived from known alcohol 17 [11][12

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• . Results and Discussion We began our work with the condensation reactions of 2-aminothiophenols 8 and bromopyruvic acid and esters 9 to form 4H-benzo-1,4-thiazines 10, having a carboxylic acid or an ester function at the C-3 position (Scheme 1). The reaction of thiol 8a with bromo-substituted acid 9a in

• classical conditions as well as under MWI. The acid 10aa could not be formed even when 2,2'-disulfanediyldianiline was used as the starting material in DMF or ethanol at room temperature or under reflux. Thiol 8a reacted with the keto ester 9c in ethanol to form the ester 10ac with a yield of 51% and 29

• formed in 50% yield in ethanol and 30% in diethyl ether (Table 1, entries 10 and 11). Reactions with thiol 8c, having an electron-donating methoxy group, and acid 9a or esters 9b,c only gave unidentifiable decomposition products in various solvents (ethanol, diethyl ether, methanol, and CH2Cl2) at

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• % isolated yield, along with some amount of the alkene complex (see Scheme 4). In an attempt to increase the yield of the cysteine derivatives, the amount of the thiol was doubled. Unexpectedly, this resulted in the inversion of the diastereomeric ratio (entry 2 in Table 2). To find a reason, the experiment

• , the (R,S):(R,R) diastereomeric ratio was changed from 1:1 to 13:1 in favor of the thermodynamically more stable (R,S) diastereomer. The experiment with thiophenol performed under the same reaction conditions (a two-fold excess of thiol and the Et3N additive) gave the cysteine derivatives in 88% yield

• and with 12:1 diastereoselectivity; again, the (R,S) diastereomer was the dominant (entry 4, Table 2), in line with the previous results with tolylthiol. In case of an aliphatic thiol (benzylthiol), the results were qualitatively similar. The diastereomeric ratio is inverted in favor of the

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• later revised as that of (Z)-4. The same compound is also observed in S. olivaceus [10] and was reported to function as a competitive inhibitor of glutathione S-transferase [11], which may be a result of a thiol addition of glutathione to the Michael acceptor in 4. While the relative and absolute

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• available cholic acid, which was converted to its cholyl hydrazide (1) as previously reported by us [21]. The produced cholyl hydrazide 1 was heterocyclized to 1,3,4-oxadiazole-2-thiol 2 in excellent yield (93%), via the treatment with carbon disulfide and trimethylamine in refluxing ethanol (Scheme 1) [33

• ]. Having oxadiazole-2-thiol 2 at hands, the reactive thiol was subjected to the reaction with propargyl bromide and sodium carbonate as a base to afford the thiopropargylated derivative 3 in 82% yield after 24 h (Scheme 2) [33]. Compound 3 was the starting point for a Mannich reaction to generate a library

• of this library will be reported in due course. Biologically active cholic acid hybridized with different heterocyclic scaffolds. Structures of target compounds 4a–v. Synthesis of cholyl 1,3,4-oxadiazole-2-thiol 2. Synthesis of cholyl 2-(propargylthio)-1,3,4-oxadiazole 3. Synthesis of target

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• radical addition of a thiol-based stopper to the α,β-unsaturated carbonyl unit in 12% yield. In this reaction, addition of the thiyl radical to the β-position first gives rise to the corresponding rotaxane radical with the unpaired electron in the α-position, followed by hydrogen abstraction from the next

• thiol. This generates a new stereocenter in the α-position, which takes place under the chiral environment of the BINOL-based macrocycle. However, the hydrogen abstraction takes place with little stereoselectivity, so that both diastereoisomers are formed in almost equal amounts (er = 53:47, see Figure

• . Synthesis of Stoddart´s BINOL-containing [2]catenanes 18/20/22/24 by π–π recognition. Synthesis of Takata´s rotaxanes featuring chiral centers on the axle: a) rotaxane (R,R,R/S)-27 obtained by thiol–ene addition and b) rotaxanes (R,R/S)-30a–f obtained by amine oxidation. Takata´s chiral polyacetylenes 32/33

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• dispirocyclopentanebisoxindoles from two molecules of 3-phenacylideneoxindoles, accomplished by reduction of one molecule of 3-phenacylideneoxindole by thiol [24]. In 2017, Thennarasu et al. [25] reported the tandem oxidation/Michel-aldol reaction of 3-phenacyloxindoles for the synthesis of dispirocycliopentanebisoxindoles

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• naturally occurring HDAC inhibitors contain sulfur moieties like, e.g., disulfides or thioesters. They seem to lack a zinc-chelating group at first sight, but the disulfide or thioester acts as a prodrug and are reduced/cleaved in vivo to liberate the free thiol, a strong Zn-binding group [24][25]. Results

• the removal of metathesis catalysts is the formation of Ru-DMSO complexes, which do not eluate from a silica column [56]. This allowed us to remove at least the Ru contamination, but we were unable to subject 12 to further modifications such as cross metathesis or thiol-ene click reactions due to poor

• modifications, mainly for solubility reasons. Therefore, we decided to have a closer look into modifications of the longer side chain present in 11 and subjected it to thiol-ene click reactions. Since masked thiols are often found as zinc-coordinating functionalities in HDAC inhibitors, e.g., in the largazoles

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• afforded the thiol compound 3nb. Further treatment of the thiol 3nb with methyl glyoxylate in dichloromethane solvent along with molecular sieves (4 Å), followed by in situ acetylation using Ac2O, pyridine, and catalytic 4-(N,N-dimethylamino)pyridine (DMAP) provided compound 37. The second route involves

• reaction with ʟ-menthol, afforded the relevant thiol-substituted esters 54, which further reacted with sulfuryl chloride to give compound 55. The reaction of compound 55 with vinyl acetate constructed a sulfur–carbon bond and produced 3k. The sulfuryl chloride reagent simultaneously allowed for

• synthesis of lamivudine (1) and the opposite enantiomer 1a was demonstrated by Han et al. [57]. They carried out the [1,2]-Brook rearrangement of silyl glyoxylate 61 using thiol 3nb as the nucleophile. Under optimized conditions, the reaction of the key intermediate 62 with acetyl chloride in ethanol

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• photoexcitation the CuI acetylide A undergoes a SET process to form the CuII phenylacetylide species B and a superoxide radical anion. In parallel, under irradiation the homolytic S–S-bond cleavage in 2-aminothiophenol dimer 38 forms thiol radicals 40. The nucleophilic addition of the amino group in radical 40 to

• the CuII acetylide B generates the CuIII acetylide species C, which coordinates with the thiol radical to give the CuII-aminothiophenol complex D. Finally, the intermediate CuI-aminothiophenol complex E reacted with HCl and O2 to generate the C(sp)-S coupling product 39 (Scheme 19). 3.4

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• photocatalysts have been successfully applied in both small- and large-scale synthesis such as organic reactions [16][17], free radical polymerization (FRP) [18][19][20], controlled radical polymerization (CRP) [21][22], CuAAC chemistry [23][24][25], and thiol–ene chemistry [26][27]. However, most of the

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• to re-participate in the reaction (Scheme 15b). There are several uses of sulfoxides as a thiol-free sulfur source for introducing sulfur at the indole C3 position [84][85][86]. In 2013, Hamashima reported a synthesis of di(indol-3-yl)sulfide (105a) by reacting indole with DMSO in the presence of

• treatment with ferrocyanide. A Cu powder-mediated reduction gives the N-protected bis(indol-2-yl)tellane 147. The final desulfonated product 148 is a potent thiol peroxidase reducing agent [100]. The benzenoid C4 and C7 linkages The syntheses of bisindolyl non-metallides connected through benzenoid rings of

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• effect highly selective aldol reactions of simple ketones and aromatic aldehydes in flow [106]. Photoinduced thiol–ene coupling was used to tether the catalyst onto silica particles, yielding an easily handled powder which was packed into a short stainless steel column (Scheme 8). The resultant packed

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• were not fully consumed. The superior reactivity of glycosyl fluoride α-1a in liquid SO2 compared to other halides was clearly demonstrated when thiol 2c was used as an acceptor (Table 3, entries 4–6). S-Mannoside 3c was isolated from mannosyl fluoride α-1a in twice as high yield as from the

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• solvent to successfully furnish 5,6-disubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones 89. Similarly, excellent yields were obtained when the thiol was replaced by malononitrile (51) even in the absence of catalyst or any promoter. The malononitrile undergoes hydrolysis forming an amide, thus giving rise

• thiol to intermediate A results in the formation of intermediate B. An intramolecular cyclization followed by dehydration of intermediate B ultimately produces 89. On the other hand, intermediate C is formed by the Knoevenagel condensation between arylglyoxal and malononitrile. This is followed by the

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• from 9, followed by a series of proposed spontaneous reactions [5][8]. Through these transformations, acid 10 can undergo a dimerization with elimination of water to allicin (5). The hydrolysis of 5 results in allylsulfinic acid (12) and allyl thiol (13), the latter of which can react with another

• ), allyl methyl trisulfide (32), and traces of diallyl trisulfide (3) and allyl methyl tetrasulfide (34) were observed. The formation of these compounds is explainable by the deallylation of DAllSP to 3-(allylsulfanyl)propanoic acid (37) and further degradation to allyl thiol (13) through the enzymes of

• the demethylation pathway that is fully established in P. inhibens by genes coding for DmdA–D (Scheme 4A). In the presence of air thiol 13 can then undergo an oxidative dimerization, or react analogously with MeSH to form allyl methyl disulfide (30, Scheme 4B). Similar oxidations requiring one

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• nucleophiles [27][28][29][30]. Thionaphthols, however, are overlooked in sulfa-Michael addition reactions. And to our best knowledge, no study is present concerned with SMAs with naphthalene-1-thiol as the nucleophile for the addition to enones. Encouraged by the good results obtained with enantioselective

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• receptor (β2AR) [29]. In this work conjugation of the CF3 group to an aromatic ring was shown to give rise to substantially improved 19F NMR chemical shift sensitivities over the more traditional thiol-specific trifluoromethyl tags (Figure 3b) [28]. In addition to chemical modification, novel methodologies

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• stereochemistry as catalysts [27]. The stereochemical properties were sensitive to the linker size and length, and the yield of the syn-head-to-tail-9,10:9',10'-cyclodimer could reach 97–98%. Traditional thiol-functionalized organic ligands decorated on the surface of gold nanoclusters (AuNCs) tend to generate a

• between thiol-functionalized β-CD and oleic acid-protected CdS nanocrystals [29]. These spherical CdS–CD nanoparticles could be employed as a photocatalyst for the dehydrogenation of alcohols to aldehydes (at a low concentration of the reactant of 1 mM, ≥92% selectivity) or diols (at a high concentration

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• the vast majority of cases, the SRF group is not installed as an intact functional group but rather indirectly through perfluoroalkylation of a thiol or sulfide moiety already present on the substrate (Scheme 1a) [15][20][21][22][23][24][25][26]. By contrast, direct perfluoroalkylthiolation, which

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• reversibly change the properties of the cell. For example, we have shown that synthetic receptors appended with a thiol or a folate group enable bacteria expressing the His-tagged outer membrane protein C (His-OmpC) to bind to gold surfaces or cancer cells, respectively [2]. We have also shown that this

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• of thiol C, which can lose sulfur, giving rise to the final product. Because of the unsymmetrical nature of substrate A, the attack on the C=S bond of HFTA proceeds by either nitrogen atom of the imidazole ring, resulting in the formation of two isomers for compounds 2–4 and 7. The highly selective

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• tendency to migrate and a generally higher stability with respect to thiol-containing AuNPs [37][38][39]. A further advantage is the straightforward ligand synthesis, which does not require the use of protecting groups as in the case of thiols. The ligand 1 served as the solubilizing component and was