Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• unprecedentedly highly oxygenated five-membered D-ring. These compounds exhibit potent anti-inflammatory and analgesic activity both in vitro and in vivo [44]. The synthetic method for the preparation of dactylicapnosines A (63) and B (64) was based on the known phenol 65 and involved the ring contraction of p

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• minerals, cleaning products, personal care products, plastics, fertilizers, and lifesaving medicines along with deleterious substances including drugs of abuse and environmental toxins. For deleterious substances that enter the human body, in vivo antidotes are required. For example, naloxone is a well

• known antidote that counteracts the effects of opioid overdose by interacting with the opioid receptor, whereas the γ-cyclodextrin derivative sugammadex (Figure 1) is an in vivo sequestrant for neuromuscular blocking agents rocuronium and vecuronium and blocks their action at the nicotinic acetylcholine

• functionalized and can flex their methylene-bridged glycoluril oligomer to accommodate guests of different size. Water-soluble acyclic CB[n] have been used as in vivo sequestrants for drugs of abuse, neuromuscular blockers, and anesthetics and as solubilizing agents for pharmaceuticals [31][32][33][34][35][36

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• . 7, H-1031 Budapest, Hungary Center for Pharmacology and Drug Research & Development, Department of Pharmaceutical Chemistry, Semmelweis University, H-1085 Budapest, Hungary 10.3762/bjoc.21.169 Abstract Motivated by the in vivo anxiolytic activity of previously described 1,2,3-benzothiadiazine 1,1

• -dioxides and their 3,4-dihydro derivatives 2 (R3 = Me) were found to have remarkable in vivo anxiolytic activity [12], we aimed to prepare further congeners exhibiting a higher potency in this field. It is well known that synthetic as well as naturally occurring compounds containing an indole moiety

• -zero sample. The natural logarithm of the percentage remaining was plotted against incubation time to determine the first-order elimination rate constant (k) using linear regression. The half-life (t₁/₂) was calculated using Equation 4: Intrinsic clearance (Clint) was calculated and scaled to in vivo

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• [5,6,1-jk]carbazoles possessed exceptionally high in vitro and in vivo antitumor potencies though topoisomerase II inhibition (Figure 1, bottom) [20]. Taken together, an emerging evidence points to the remarkable pharmacological versatility of indolo[1,2-c]quinazoline derivatives, highlighting the need

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• [40] activities. Furthermore, a quinoxaline-containing commercial drug, caroverine, has been proven effective in the treatment of tinnitus [41]. In addition, in vivo studies in mice and rats with various quinoxalinone derivatives have shown favorable analgesic and anti-inflammatory properties as well

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• effects. The azo-calix[4/5]arenes have demonstrated strong binding capabilities with a range of chemotherapeutic drugs, which underscores their potential as supramolecular drug carriers. They have verified the efficacy of this hypoxia-targeted therapy through both in vitro and in vivo experiments, and the

• -DM) or fingolimod (FTY720) in vitro. Upon local administration, the hypoxia-responsive self-assembling peptide hydrogel resulted in improved motor function and reduced inflammation in vivo. Recently, Geng and colleagues created additional binding sites by modifying the upper rim of CA4 with glucose

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-a]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1) as a

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• dihydrochloride salt of the alkaloid has been tested in vivo in rats, cats, and rabbits as an antiarrhythmic agent, demonstrating superior efficacy compared to the commercially available drugs quinidine and novocainamide [34]. N-Methylbrevicarine, a semi-synthetic derivative of the alkaloid, has been screened in

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• development targeting iNOS-related pathologies. Future research should prioritize extensive in vivo studies and clinical evaluations to further explore their therapeutic potential and safety profiles. Experimental Experimental methods All chemicals were purchased from Merck, Sigma-Aldrich and Acros without

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorescent protein (GFP), has revolutionized genetics by providing highly accurate real-time detection of fusion proteins in vitro and in vivo [1]. Pioneering work on GFP-tagged proteins for real-time monitoring of gene expression was first reported by Chalfie and co-workers in 1994 [2]. For a long time

• better solubility in the reaction buffer and did not require DMSO as co-solvent, making it a very promising candidate for in vivo applications. To complete the study, and given that the mesyloxy group has shown superior efficacy over all other functional groups tested for Pepper alkylation, we

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• acyclic CB[n] are not macrocycles, they are preorganized into a C-shaped geometry by virtue of their polycyclic chemical structure and display binding affinities approaching those of macrocyclic CB[n]. M1 and analogues display outstanding biocompatibility and have been used for a number of in vivo

• biomedical applications including as a solubilizing excipient for anticancer agents and as an in vivo sequestrant to reverse the biological activity of neuromuscular blocking agents, anesthetics, and drugs of abuse (e.g., methamphetamine and fentanyl) [54][55][56][57][58][59][60]. As a result of their

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• candidates for further in vitro and in vivo testing as antifungal prodrugs. Experimental General procedure for preparation of N-R-7-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-5-carboxamides 4a–i: A mixture of 2-aminoimidazole hemisulfate (1, 0.66 g, 5 mmol), N-substituted maleimides 2a–i (5 mmol), sodium

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• electron-donating group at the 4′-position, are good candidates for further evaluation in vitro and in vivo, after validating possible sunscreen formulations which improve the effects in a synergistic way. We believe that this work will open up avenues towards evaluating 5′-substituted 2

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• H-iPr-nicardipine was higher (8 min) related to enhanced ester stability with an isopropyl group versus a methyl ester. Collectively these results point to high potential for translation in vivo where novel deuterated analogs exhibit longer t1/2 and by extension oral bioavailability. Conclusion In

• selective deuteration of often metabolically soft benzylic C–H sites. Lastly and most importantly, preliminary surrogate metabolic stability studies on site selective [D1]-DHPs suggest these novel deuterated analogs may afford increased exposure in an in vivo setting. The methodology is likely to have wide

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• , batch-to-batch reproducibility, and reliable kinetic modelling of the system [10][11]. Furthermore, the transferability of CFPS screening results to the cells is limited but important, as in vivo production is often required for preparative scale applications [11][12]. To date, the description of CFPS

• [66]. Purity of the in vivo produced proteins was checked with sodium dodecyl sulfate polyacrylamide gel-electrophoresis (SDS-PAGE) [67]. Impurities were quantified with ImageJ [68] and measured protein concentrations corrected by the results to gain concentrations of pure sfGFP and thscGAS-sfGFP

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• substitution patterns are different (Figure 1). Natural alkylpyrroles were shown to have cytotoxicity [27], antidiabetic activity [28], anti-lipid peroxidation [12], in vivo antihypoxic activity [12], and antibacterial activity [15]. Though not impressive in cytotoxicity and tyrosinase-inhibitory evaluations

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• )-[3H]-baclofen displacement. QSAR studies have been developed in order to examine the pivotal role of the aromatic moiety of baclofen-like compounds [25]. In this sense, the QSAR equation revealed HOMO/LUMO orbital energies are critical for a high correlation with binding strength. An in vivo

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• -free conditions at room temperature for 2 h [16]. Although thiamine had already been reported to be effective in other chemical transformations and its role in carbonyl activation in vivo through its thiazole ring is well known, no mechanism of action in the GBB condensation was proposed by the authors

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• identification” (Scheme 5B) [52][53][54]. In addition, the utilization of MaDA allowed the chemo-enzymatic total synthesis of 3 and related natural products (Scheme 5C). To identify the Diels–Alderase (MaDA), the research group initially demonstrated an in vivo enzymatic reaction by treating chemically

• catalysis with chemical synthesis [86]. By taking advantage of the chemo-enzymatically accessible 4, Sherman and co-workers further implemented the systematic total synthesis of juvenimicins and the M-4365 series via enzymatic and chemical late-stage modifications (Scheme 8B) [68]. In vivo glycosylation

• mechanism of tylactone (4) in Streptomyces fradiae. (A) Chemical synthesis and cascade enzymatic transformations of cyclization precursors. (B) Late-stage modifications of chemo-enzymatically synthesized aglycone 4 utilizing in vivo/in vitro enzymatic transformations and chemical conversions. Proposed

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• the tyrosine and isoleucine side chains, and then N-methylation is installed by UstM on the N-terminal tyrosine residue [91][92]. Another member of the dikaritin family is phomopsin. All phomopsins contain at least one N-methylated tyrosine. In vivo studies have attributed the MT activity to PhonM

• promising potential for biocatalytic applications, accepting a wide range of different precursor substrates. In many cases, these substrate scope analyses are performed by co-expressing different precursor peptides with the MT – in such in vivo systems, SAM supply or SAM regeneration is not required

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• as direct substrates for AlpJ-family oxygenases. However, the dominant biosynthetic pathway in vivo remains unclear. Given that 8 has been experimentally validated as the authentic product of the JadH/AlpG-catalyzed reaction, it is recognized as a bona fide intermediate in angucycline biosynthesis

• [25]. On the other hand, the origin of 1, spontaneously derived from 8 under aerobic conditions, raises uncertainties about the actual production in vivo. Furthermore, the significance of the C12 hydroxy group in the hydroquinone intermediate 11 is evident in subsequent reactions, including the

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• characterized using in vitro assays. The in vivo activities of MSTSs were revealed by the development of an efficient precursor-providing chassis. The inherent features of MSTSs not only increase the structural diversity of terpenoids but also underscore their potential for generating new terpenoids through

• ][20], and C15 and C20 [18]. For instance, PamTps1 from Plectranthus amboinicus (Lour.) Spreng has been characterized as bifunctional in converting compounds 3 and 4, respectively, to 6 and 7 both in vivo and in vitro (Table 1) [17]. In addition to the bifunctional plant TSs, a few plant MSTSs have

• enzymes (Table 1) [18]. A TPS-f subfamily enzyme CoTPS5 from Cananga odorata has been characterized to convert 3 to (E)-β-ocimene (9), 4 to 8, and 5 to diterpene α-springene (10) (Figure 2) [22]. Both in vitro assays and in vivo transgenic expression of CoTPS5 confirmed the absence of side products

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

• noursei, an NNG-producing bacterium, did not reveal any NnlA homologs. Interestingly, four NMOs are annotated in the S. noursei genome. These enzymes could protect S. noursei from NNG toxicity during its biosynthesis. Meanwhile, we posit that NnlA protects non-NNG producing bacteria from exposure. In vivo

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• more closely, eight compounds were chosen for this study (Figure 4a). Due to the insolubility of CavA in E. coli, the study employed in vivo substrate screening. The S. avermitilis SUKA22 DL10089 was cultivated in XTM medium with the supplement of various substrates for five days. HPLC analysis

• of DMTs. The in vivo experiments further expanded the substrate scope of CavA to include albicanol (5) and drim-8-ene-11-ol (6), showcasing the enzyme's biocatalytic potential. This study establishes a foundation for biocatalysts targeting the A-ring of drimenol, which might be beneficial for the

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

• [8]. Further improvement of the PDT method requires the search for new photosensitizers having higher photoactivity, tumor selectivity, and high singlet oxygen quantum yield, as well as low in vivo toxicity [7]. Therefore, some strategies have been developed to enhance the therapeutic efficiency of

• compounds in drug development [34][35][36][37]. Owing to their stability, carboranes also may increase the in vivo stability and bioavailability of pharmaceuticals that might otherwise rapidly metabolize [38]. The functionalization of porphyrins with carborane clusters provides dual-action photo(radio