Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• formation of propionate 3-nitronate (P3N) as a conjugate base (Scheme 2) [39]. It is P3N that directly reacts with a cysteine in the ICL1 active site, forming a thiohydroxamate adduct that inhibits ICL1 turnover [40]. Additionally, the nitronate form of nitro acids has been proposed to behave as a

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• has become one of the most popular route for the site-selective modification of cysteine residues in bioconjugation technology. We suppose that the maleimide group in porphyrin 11 is a useful target for thiol conjugation via Michael addition reactions [44]. This also concerns biotin-conjugated organic

• cytoprotective and therapeutic actions. It is synthesized from cysteine and is excreted without any further metabolism [47]. The reaction of taurine (25) with porphyrin 6 proceeded in DMSO at 20 °C for 72 h to afford taurine-containing conjugate 26 in 78% yield (Scheme 6). Conjugates 19, 23, 24, and 26 can be

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• inspired by the use of ʟ-proline-modified magnetic nanoparticles reported by Khalafi-Nezhad et al., synthesized nano-Fe3O4@ʟ-cysteine for the green synthesis of BIMs, employing microwave irradiation to avoid long reaction times [117]. A mixture of the reagents and 100 mg of nano-Fe3O4@ʟ-cysteine per 1

• the nano-Fe3O4@ʟ-cysteine particles being magnetically recoverable in a facile manner. The reaction could also be realized with conventional heating at 80 °C, however, the reaction rates were more than 20 times lower, and ketones displayed unappealing conversion rates. The mechanism of action follows

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

•  6) [75]. One-pot double annulations for the synthesis of tetrahydropyrrolothiazoles The unique tetrahydropyrrolothiazole and spiro[indole-tetrahydropyrrolothiazole] scaffolds are found in bioactive compounds such as those shown in Figure 7 [76][77]. Using cysteine as a key reactant, we developed a

• pseudo-four-component reaction for the synthesis of tetrahydropyrrolothiazole derivatives. The reaction of cysteine with two equiv of arylaldehydes and one equiv of maleimides in EtOH at 90 °C for 12 h afforded tetrahydropyrrolothiazoles 29 in 66–79% yields with up to 7:1 dr (Scheme 17) [76]. Using

• olefinic oxindoles to replace maleimides, the reactions gave spiro[indoline-tetrahydropyrrolothiazole] products 30 in 55–70% with greater than 4:1 dr [76]. The reaction mechanism suggests that the reaction of cysteine with arylaldehydes gives N,S-acetals 27 which convert to AMYs 28 after decarboxlyation

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory

• by acid hydrolysis of 1 using the method developed by Tanaka et al. [16], in which the hydrolysates are derivatized with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. For compound 1, peaks were observed at retention times of 13.96, 20.83, and 22.16 min. The peaks at

• residue was added a solution of ʟ-cysteine methyl ester hydrochloride (2 mg) in pyridine (200 μL), and the mixture was stirred at 65 °C for 1 h. Then, a solution of o-tolyl isothiocyanate (2.2 μL) in pyridine (200 μL) was added and the resulting mixture was stirred at 65 °C for 1 h. The final mixture was

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

•  4), the biosynthesis starts from hexanoic acid which, upon its thioesterification, is elongated by three decarboxylative Claisen condensations with malonyl-CoA to a 6-pentylsalicyl thioester. A condensation with cysteine and a subsequent cyclization generate a 6-pentylsalicyl-thiazolinyl thioester

• intermediate (1’). In massiliachelin biosynthesis this intermediate is further processed and elongated with another cysteine-derived thiazoline, which is eventually reduced [18]. A premature hydrolytic release of 1’ from the assembly line would give 1, which could be further modified to 2–5. Some corresponding

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• complex. Solubility of the t-Bu-containing ligand and its Schiff base complexes is increased, facilitating scaling-up the reaction procedure and isolation of the functionalized amino acid. Keywords: asymmetric synthesis; chiral auxiliaries; cysteine derivatives; Ni–Schiff base complexes; voltammetry

• . Results and Discussion Synthesis The synthetic approach to the chiral ligand L7 as well as to its Ni–Schiff base derivatives containing glycine, serine, dehydroalanine, and cysteine is given in Scheme 2. Commercially available (S)-proline was used as the starting material. To obtain the starting t-Bu

• techniques; for details, see Supporting Information File 1); [α]D20 = 2127 (MeOH). To test the stereocontrolling efficiency of the new ligand L7 and to obtain new cysteine Ni–Schiff base derivatives (RCysNi)L7 which are of practical interest, complex (ΔAlaNi)L7 was involved in a nucleophilic addition as

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• development of fluorinated aminophosphonate-based inhibitors. Keywords: aminophosphonates; cathepsin C; dipeptide; fluorine; solvolysis; Introduction Cathepsin C, also known as dipeptidyl peptidase I (DPPI) belongs to the family of lysosomal cysteine proteases encompassing 11 human enzymes (cathepsins B, C

• in chemotherapies to support traditional anticancer drugs. Moreover, there is a growing interest in the topic of cathepsin C inhibition, which directly affects serine protease activity [5][6]. Inhibitors of cathepsin C can be cystatins that show activity against a large group of cysteine proteases [7

• the catalytic cysteine Cys234 [10]. Phosphonates, as well as their analogues phosphonic acids, can be modified in a number of ways, one of which is the introduction of a fluorine atom into their molecules by fluorination or alkylfluorination [11][12][13][14]. However, the reaction of β-aminoalcohols

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• of an unsaturated fourteen- or sixteen-membered macrolactone decorated by an ʟ-cysteine-derived 2-oxo-1,3-thiazolidin-4-yl substitutent, and the presence of five stereogenic centers forming a 1,2,4,6,9-stereopentade (Figure 1). In latrunculins A (1) and B (2) three of them are embedded in a lactol

• (13,14)-bond of 1 and 2, respectively. Conversely, we envisaged an alternative disconnection to form the (16,17)- or the (14,15)-bond of 1 and 2, through an aldol reaction of aldehyde 8 readily available from ʟ-cysteine, leading to aldol adduct 7 (Figure 2, route B). The methyl ketone partner 9 could be

• partner (8) for the aldol reaction brings the thiazolidinone heterocycle of the natural product. It was synthesized in four steps from ʟ-cysteine ester derivative 16, first reacting with carbonyldiimidazole (CDI) to afford thiazolidinone 17 in 85% yield (Scheme 2). The nitrogen atom was protected with a

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• 10.3762/bjoc.18.171 Abstract A novel four-component reaction in one pot as an atom- and step-economic process was developed to synthesize diastereoselectively spirooxindolepyrrolothiazoles through sequential N,S-acetalation of aldehydes with cysteine and decarboxylative [3 + 2] cycloaddition with olefinic

• PASE reactions of making spirooxindolepyrrolothiazoles are even more rare, which only involves three-component reactions with isatins and thioproline (Scheme 2A and 2B) [75][76]. Four-component double annulations through 2-substituted thioprolines formed in N,S-acetalation of aldehyde and cysteine was

•  2C). Results and Discussion The optimized reaction conditions of stepwise, one-pot and cascade (two-step with one operational step) processes for N,S-acetalation and decarboxylative 1,3-dipolar cycloaddition were developed by using two equivalents of 4-bromobenzaldehyde (1a), ʟ-cysteine (2) and

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• array, a scenario that would make it unavailable for binding to the integrin receptor in the subsequent analytical experiment. The PEG-6-linker was selected because it was effective and readily available from commercial sources. This linker was functionalized with a cysteine on the end opposite the

• used for the placement reaction, the full binding curve for the interaction between R6A and its Gαi1-target could not be observed. A method was needed to further reduce the concentration of the R6A peptide on the surface of the electrodes. To this end, cysteine methyl ester was selected as a molecule

• with which to dilute the R6A peptide because cysteine methyl ester does not show any background binding to Gαi1, and it can be efficiently placed onto the arylbromide-based surface using the same Cu(I)-catalyzed cross-coupling reaction used to place the R6A-PEG-C substrate on the array (Scheme 3). The

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• enzymatic coupling to complete the sugar nucleotide [7][8]. With this capability in place, we wished to explore the synthesis of further tools, targeting the active site cysteine residue (Figure 1c). We envisaged that access to C6–amino or C6–sulfhydryl species of type 8 would offer prospect to establish

• active site thiohemiaminal (amine to imine oxidation) or disulfide formation, respectively. Additionally, C6–Cl derivative 9 could probe cysteine alkylation. Reported herein is our exploration of this synthesis and the evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose 18 against GMD. Results and Discussion

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• system as well as a cysteine thiolate ligand from the protein backbone (Figure 1B). The generally accepted catalytic cycle for hydroxylations is shown in Figure 1C. In the resting state A, the central ferric ion is coordinated by six ligands, four from the porphyrin ring system, one cysteine thiolate

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• the covalent capsule 5 (made from resorcinarene caps connected by four dihydrazone units of ʟ-cysteine) with C60 and C70 fullerenes upon neat ball milling in a planetary ball mill (Figure 6). The mechanochemical complexation is remarkable since the porous capsule does not possess large enough openings

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

• acids. One-pot combination of the reductive ring opening and subsequent addition of thiols allows obtaining the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Keywords: amino acids; cathodic cyclopropane opening; cysteine derivatives; Ni–Schiff

• cyclopropane ring in α,α-cyclopropanated amino acids yielding the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Thus, the present paper is a further development of the extended research on electrochemically induced stereoselective transformations in the

• , alanine, serine and cysteine derivatives are formed as an antibonding combination of the Ni dx²-y² orbital with the group orbitals of the ligands; the π* orbital of the imine and the π orbital of the phenylene fragments are also partially involved. Reduction occurs at similar potential values and is

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• hydrolysis, was dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixture was stirred at 60 °C for 1 h. Then O-tolyl isothiocyanate (30 μL) was added and stirred at 60 °C for 1 h. The reaction mixture was analyzed without purification by LC–MS analysis

• using GC–MS. Monosaccharides (1, 0.4 mg; 2, 0.3 mg; 3, 0.4 mg; 4, 0.4 mg), obtained by hydrolysis, were dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixtures were then stirred at 60 °C for 2 h. After adding 1-trimethylsilylimidazole (0.1 mL

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• and sugar, respectively. The aqueous residue was concentrated to dryness under N2. The aqueous residue, ᴅ-glucose (2 mg), and ᴅ-xylose standard (2 mg) were separately dissolved in 0.5 mL anhydrous pyridine, and ʟ-cysteine methyl ester hydrochloride (2.0 mg) was then added. Each reaction mixture was

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of biomolecules [35][36][37]. The approaches by Buchwald and Pentelute are suitable for selective, bioorthogonal labelling of cysteine- [38][39][40] and lysine-containing [41][42] peptides and proteins using stochiometric amounts of pre-formed Pd(II)-aryl complexes. They can further be applied for

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• 90 °C. The hydrolysate was extracted with EtOAc and the aqueous layer was neutralized by passing it through an Amberlite IRA-67 column to give the sugar. The sugar obtained from the hydrolysis was dissolved in anhydrous pyridine (0.5 mL) followed by adding of ʟ-cysteine methyl ester hydrochloride

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• to mitochondrial protein, but also chelates other cysteine-containing species. Several hundred good binding sites for trivalent arsenicals in each organ have been proposed [6][7], and more than 50 arsenic-binding proteins could be identified and analysed by Zhang et al. [8] and Yan et al. [9] using p

• proliferation of human synovial sarcoma SW982 cells (Figure 7). All four PISA particles displayed an enhanced cytotoxicity compared to free PENAO using SW982. While PENAO’s cytotoxicity arises mainly from crosslinking two cysteine loops in the mitochondrial ANT protein, the here employed systems seem to not

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

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• % postaddition). Another approach is to use a next generation of short peptides that also bind to the transferrin receptor at noncompeting regions to endogenous transferrin in vivo [54]. These molecules are known as cysteine-dense peptides (CDPs) and have been shown to bind to the transferrin receptor in the