Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• Gianpaolo Gallo Bartosz Lewandowski Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland 10.3762/bjoc.21.42 Abstract Tryptophan fulfills a plethora of important functions in nature both in its free form and as a component of peptides and proteins. Selective

• peptides [4][5]. Tryptophan also serves as a substrate to produce hormones such as serotonin or melatonin [6][7]. Due to the biological relevance of tryptophan synthetic receptors for this amino acid are highly sought after [8]. From a biological perspective it is especially desirable to achieve selective

• binding of tryptophan in water [9]. However, the development of selective amino acid receptors in aqueous environments is challenging since it requires a combination of hydrophobic and polar interactions for binding [10][11][12]. As a result, the number of reported selective receptors for tryptophan in

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• University, Universitätsstraße 25, 33615 Bielefeld, Germany 10.3762/bjoc.21.40 Abstract Drug conjugates using toxic payloads are a promising approach for selectively combating cancer while sparing healthy tissue. The lack of highly cytotoxic and at the same time selective therapeutics against cancer is an

• 8 was obtained in good yield of 61% through reductive amination with excess formaldehyde and NaBH3CN as reductant, the selective installation of only one methyl group, providing monomethyl aniline 7, proved to be more troublesome. Either reductive amination using the same protocol, but under strict

• deaths in cancer patients and MDR-selective therapeutics are lacking [36], we expect that cryptophycins 1 and 2 will be considered as viable cytotoxins for the use in targeted tumour therapy, especially against MDR cancers. A: Structure of cryptophycin-52. B: Cryptophycin-52 derivatives modified with

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• of (R)-2-methyloxirane ((R)-2) with allylmagnesium bromide (3) catalyzed by CuI produced a mixture of (R)-hex-5-en-2-ol ((R)-4) and (S)-2-methylpent-4-en-1-ol ((S)-4’) (ratio 8:1, determined by 1H NMR spectroscopy) [25][26]. The primary alcohol (S)-4’ could be easily removed by a selective TEMPO

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• were required to obtain the corresponding mesylate 3b. Similar to 11, compound 12 was isolated as its trifluoroacetate salt. Selective Boc protection of the aliphatic amine gave 13, which was selectively O-mesylated to give compound 14. Compound 14 was found to slowly undergo intramolecular cyclization

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• photons and forces, streamlining the combination of mechanochemical and photochemical processes and paving the way for more efficient, sustainable, and selective transformations in organic synthesis. An unexplored opportunity is offered by resonant acoustic mixing (RAM) [82], a technology that leverages

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• diaryl λ3-bromanes under remarkably mild conditions with subsequent applications of the in situ-generated arynes in cycloaddition reactions [3], meta-selective reactions with oxygen and nitrogen nucleophiles [4][5], regiodivergent meta or ortho-alkynylations [6], and regioselective (di)halogenation [7

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• across many fields of selective catalysis under the term confinement [3], a term borrowed from heterogeneous catalysis. Polarization can be understood as the catalyst providing an electrostatic environment that works to stabilize electron redistribution. Since all reactions redistribute electrons, and

• a size-selective space [105][126][129][130][132][134]. A key advantage is that these capsules have been made on multi-hundred-gram scales and can be recycled [132]. Additionally, control of structural or bound water by the capsule [105] and properties such as a lowered pKa inside [125] demonstrate a

• selective substrate and transition-state binding, and for which extensive synthetic development is known [350][351][352][353][354][355]; (iii) they are the lowest possible symmetry polymacrocyclic structure (removing one edge piece will result in a macrocycle) [356][357], meaning ordered asymmetric

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• chimera (PROTAC) has made it a popular starting point to develop selective small-molecule degraders [2]. Currently, leveraging ubiquitination by the von Hippel–Lindau (VHL) protein or cereblon (CRBN) is the most successful method to achieve targeted protein degradation [3][4]. For initial studies, a short

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• . Levulinoyl protection: Levulinic acid (Lev, 27) as protecting group which can be cleaved using hydrazine hydrate in AcOH, also yields highly selective 1,2-trans glycosides [95][96] and was implemented as a substitute for acetyl or benzoyl protection [97][98]. van Boom et al. also showed the use of a masked

• levulinoyl protecting group, the 4,4-(ethylenedithio)pentanoyl group 28 [99]. Wong and co-workers illustrated the selective activation (Scheme 5) of C-2 levulinoyl-protected thiotolyl glycopyranosyl donor 29 for the synthesis of the disaccharide fragment 31 of fucosyl ganglioside GM1 [100]. Pivalate

• themselves from the other ester-type protecting groups, thereby enabling selective orthogonal deprotection strategies. Such protecting group showing orthogonality with acetyl protection is the chloroacetyl protecting group [109][110][111]. It renders similar neighbouring group participation by employing the

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• prepared scaffolds are valuable additions to the class of pyrazolo-1,2-benzothiazine antibiotics with selective antistaphylococcal activity. Keywords: acetamides; antibiotics; antimicrobial; benzothiazines; Staphylococcus aureus; Introduction The global crisis of antibiotic resistance has been

• /cancer and other CAs (I, II). Non-selective inhibitors may have certain adverse effects so selective CAIs are worthier and more valuable [57]. Results of hCA inhibition assays are listed in Table 3. It was observed that the dialkylated pyrazolobenzothiazines 7i–n failed to inhibit any of the four

• CA II, 7c for CA IX, 7d for CA II, CA IX and CA XII, and 7f for XII. However, compound 7e appeared to show low but selective inhibition against the two transmembrane and tumor-associated forms (CA IX and CA XII) with Ki values of 82.6 and 88.4 µM, respectively and no inhibition against CA I and CA II

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• , making it particularly suited for large-scale applications. Recent advances highlight the unique advantages of both metal-based and metal-free catalysts under red-light irradiation, broadening the range of possible reactions, from selective oxidations to complex polymerizations. In biological contexts

• sustainable photocatalysis, with applications ranging from selective oxidation to cross-dehydrogenative coupling. These organic systems are valued for their reduced environmental impact, their wide availability, and tunability, making them viable alternatives to traditional metal-based catalysts for red-light

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• -donating bis(methoxyphenyl)amino groups further improved the PLQY to 73%, displaying a mixed excitonic and charge-transfer character [22]. Additionally, the functionalization of BPP with two methyl benzoate groups enabled the development of hole-selective contact, which was applicable in significantly

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• participation of the C=C bond. Apparently, the ratio of the adducts of the Diels–Alder (i.e., I) and the hetero-Diels–Alder reaction (i.e., II) was strongly influenced by steric factors; a decreased steric hindrance in the initial CH acid derivatives led to a more selective formation of the structures I. This

• [27]. The three-component reaction with acetoacetic ester was highly selective, and the formation of a minor [4 + 2]-cycloaddition product was not observed (according to 1H NMR spectroscopy), but the yield of the products 15 did not exceed 9%. For acetylacetone, the reaction was the least selective

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• measurements (Figures S20 to S25, Supporting Information File 1). A notable feature of this cascade process is the temporary protection of the C≡N triple bond, nitrile in the key intermediate 11, by the 2,3-diaminobenzofuran group. This facilitates the site-selective activation of the alkyne triple bond by the

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• activation of propargylic aldehydes with catalyst Int-1. Another critical feature was the ability of the organocatalyst to promote the Z-selective isomerization of Int-2 to Int-3. In a related fashion, Wang and co-workers developed an atroposelective heterocycloaddition [19]. The iminium-activated alkynals 4

• acylazolium intermediate Int-16 followed by E-selective protonation of Int-17 (Scheme 9). NHC-catalysis also proved useful in the atroposelective construction of triaryl derivatives with two stereogenic axes. Wei, Du, and co-workers developed a synthesis of 1,2-diaxially chiral triarylpyranones 29 via an NHC

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• -flow pattern using a Y-shaped mixer, followed by the suspension of the catalyst via a T-mixer. This technology was utilized to develop selective and efficient decarboxylative fluorination reactions. Recently, a slug flow platform was developed (Figure 3a) by injecting segments of gas as a separating

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• challenging, if not impossible. In order to overcome this problem, we opted to synthesize benzo[j]fluoranthene analogues with differentially protected oxygens so that specific positions can be functionalized further if needed after selective deprotection. To this end, first we accomplished an efficient

• synthesis of benzo[j]fluoranthene 23 in six steps (Scheme 3). In this sequence, 1,8-DHN (19) was first converted to 1-acetoxy-8-methoxynaphthalene (24) via a selective mono-methylation of 19 followed by acetylation by acetyl chloride in 88% yield over two steps. The more electron-rich ring of naphthalene 24

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• efficient and selective extraction of lanthanides and actinides and, furthermore, a number of heterocycles involving pyridine rings have been reported to exhibit biological activities [14][15][16][17][18][19][20][21][22]. We have recently reported, as shown in Figure 1, that the introduction of a multiply

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• on an intramolecular Michael addition carried out in DMF and catalyzed by 10% of potassium carbonate. As previously observed [37], under these conditions, the 5-endo-trig cyclization was selective and the lactam resulting from the 5-exo-trig cyclization was not observed. Furthermore, in the case of

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• , cholinesterase inhibition (human BuChE, hBuChE), Aβ1-42 self-aggregation inhibition, and antioxidant activity. FATH 5a (Scheme 5) emerged as a promising candidate, showing lower hepatotoxicity at 1000 µM (59.4%, 1.72-fold less toxic than tacrine), moderate and selective hBuChE inhibition (IC50 = 68.2 nM), strong

• new selective non-cannabinoid ligands due to the important motor impairment found in mice lacking GPR55 [51]. In this context, ML192 analogs were synthesized employing a divergent synthetic route starting with a multicomponent reaction, the Gewald reaction (Scheme 13). This reaction allows to easily

• heterocyclic core. The novel compounds were first evaluated using β-arrestin recruitment assays in CHO (chinese hamster ovary) cells overexpressing human GPR55. These new compounds have been evaluated in competitive binding assays for cannabinoid receptors, but all of them showed to be selective for GPR55 (>4

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• oligomerizations involving [1.1.1]propellane – i.e., to make [n]staffanes – has been notoriously challenging to control when n > 1 is desired. Herein, we report selective syntheses of SF5- and CF3SF4-containing [2]staffanes from SF5Cl and CF3SF4Cl, demonstrating cases whereby oligomerization is preferentially

• substituted BCPs [25][26][27] or photochemical appendage of 1 onto an extant BCP [28][29][30][31] are relatively effective tactics for the selective assembly of certain [n]staffanes; the main caveat is that multiple synthetic steps are required. On the other hand, while a one-pot radical chain oligomerization

• synthetic challenge. Herein, we report proof-of-concept that our previous work on strain-release pentafluorosulfanylation of 1 [36] using SF5Cl (prepared in house [37] under mild oxidative fluorination conditions [38][39][40][41][42][43][44]) can be extended to the selective synthesis of the associated

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• cost effective and selective, one-pot transformation. Pharmaceutical uses for bio-active cyclic molecules accessible by I(III) reagents are plentiful; anticancer drugs can be formed from the basis of pyrrolo[2,3-b]indoles 1 [3][4], 2-oxazolines 2 [5][6], dihydrofuran 3 [7][8], and spirocyclic scaffolds

• . The level of this chemoselectivity was dependent on the iodane ligand: OPiv was more selective for aminofluorination than OAc, which was proposed to be due to differences in basicity and nucleophilicity (Scheme 10). Detailed mechanistic studies were carried out using multinuclear NMR spectroscopy

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , along with electrostatic and hydrogen-bonding interactions. This behavior not only allowed for the selective activation and deactivation of organocatalytic activity but also facilitated efficient catalyst recovery at the end of the catalytic reaction. Notably, control experiments supported the

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• representative studies include antibacterial, anti-inflammatory, antioxidant, selective inhibitor of COX-2 [34], and anti-HIV activity [35]. In this context, even though indole is considered a privileged scaffold present in some anticancer agents [36], a few examples of methanesulfonylindoles are studied as