Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• architecture. Although extensive research has explored its pharmacological properties and various synthetic approaches, significant challenges remain in the efficient synthesis of borrelidin and its analogs. Existing literature largely focuses on total synthesis, bioactivity, and structural modifications

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• -inducing properties in peptides [22][23][24]. Furthermore, derivatives of pipecolic acid are known for their bioactivity as secondary metabolites [25][26][27] and for being building blocks for piperidine alkaloids [28] with a variety of uses. Results and Discussion Addressing specific positions in the ring

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• ]. This molecule is a ring-expanded analogue of proline, and derivatives of it are found within several natural products and drugs. The pucker of the six-membered ring of 96 is quite important for bioactivity, because different puckers project the carboxyl substituent in different orientations (equatorial

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• compounds that generally enhance the bioactivity of agrochemical and pharmaceutical substrates. On the other hand, 5-aminopyrazole [11][12] is a nitrogen heterocycle that has attracted significant interest to pharmaceutical and medicinal chemists due to the presence of this nitrogen heterocycle in various

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

• inductive methylation [24]. To research further the bioactivity of the pheromone, herein, we report an effective synthesis of the aggregation pheromone of T. castaneum, which uses the cheap (R)- and (S)-2-methyloxirane as chiral sources, connects two chiral building blocks through Li2CuCl4-catalyzed

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• designed with a PhCF2 group (Figure 1a) [8][9][10]. As a result, there is a pressing need for the development of efficient methods for incorporating both the CF2H and PhCF2 groups into diverse molecular frameworks, particularly those with bioactivity properties. The benzimidazole core is widely recognized

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• potential bioactivity [70][71][72][73]. Despite the development of synthetic approaches for six-membered lactams, including transition-metal-catalyzed transformations, several limitations remain, particularly with regard to regioselectivity and asymmetric C–N bond formation, which are still limited. In 2023

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• –activity relationship data, leading to speculation over the moieties responsible for their antibiotic effects. A reduction in the number of amines in the polymeric chain and the absence of a primary amine was noted to decrease bioactivity by Xu et al. [7]. Research reported by Khan et al. in 2014 [9] also

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

• primary and secondary pharmacophores. Inspired by the structure and bioactivity profile of aripiprazole, a novel series of DRD2-biased agonists have been developed. The study involves the design, synthesis, and pharmacological characterization of DRD2 partial agonists [68]. Employing Ugi and Ugi post

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

• bioactivity study was proposed based on observations that indole-coumarin-thiadiazole hybrid compounds described by Kamath et al. [44], as well as indole-benzimidazole hybrids reported by Singla et al. [45] have shown potential as therapeutic agents for breast cancer treatment. Thereby, we hypothesized that

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• Thomas Ma John Chu Department of Chemistry, National Taiwan University, Taipei City 10617, Taiwan 10.3762/bjoc.20.253 Abstract Bioactivity-guided fractionation (BGF) has historically been a fruitful natural product discovery workflow. However, it is plagued by increasing rediscovery rates in

• invention of the bioactivity-guided fractionation (BGF) workflow by Selman Waksman to search systematically for new bioactive small molecules (Figure 1) [11]. He believed that the fungus Penicillium rubens produces penicillin to suppress the growth of other microorganisms, especially those it competes with

• of almost any bioactivity of interest that originate from plants, fungi, and even animals (such as sponges and corals). Perspective BGF can access only a fraction of the natural product chemical space For nearly a century, BGF has been the method of choice and identified the vast majority of natural

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

• ]pyrimidines thus formed did not show significant bioactivity, they found applications as additives in electrochemical copper plating processes [21][22] (Figure 2). Based on the above, the main goal of this work was to develop a convenient method for the construction of potentially pharmacophoric imidazo[1,2-a

• this work was a preliminary evaluation of the potential bioactivity of the obtained compounds. In particular, a molecular docking experiment to investigate the binding mechanisms to the CYP51 enzyme and an evaluation of the antifungal activity of imidazo[1,2-a]pyrimidines against Candida albicans were

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• -amines and it was exemplified through the preparation of a focused chemical library with 19 members. In addition, the cytotoxicity assays afforded interesting results demonstrating that the substitution on the anilino part can have significant effects on their bioactivity. Two molecules (4a and 4i

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• ), antituberculosis agents [13], as well as in drugs against arrhythmia (nesapidil) or muscular dystrophy (ataluren) [21]. The 1,3,4- and 1,2,4-oxadiazoles are the most promising from the point of view of bioactivity among the four isomers of oxadiazole. The presence of a 1,3,4-oxadiazole ring in the structure of

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

• [31]. Range-separated hybrid GGA (RSH-GGA) functional, including dispersive interaction with 6-31G* as the polarization basis set (ωB97X-D/6-31G* method), was used for energy and geometry optimization [32]. Bioactivity Cytotoxicity and tyrosinase assays were carried out according to the procedures

Novel oxidative routes to N-arylpyridoindazolium salts

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

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• exhibit significant bioactivity [4] and can be used as intercalating agents [7]. The very limited scope of these practically useful compounds is mainly attributed to the lack of convenient synthetic approaches to them. Thus, the only example of N-arylpyridoindazolium salts was obtained via intramolecular

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• . These peptides were expressed in an E. coli host and produced in sufficient concentrations to perform bioactivity assays. The C39-associated domain was purified to facilitate the transformation from pre-peptide to the mature configuration. The mature clostrisin and cellulosin exhibited antimicrobial

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• ; fluorobenziodoxoles; halogen bonding; hypervalent iodine; Selectfluor; Introduction An important strategy in the drug discovery process is the incorporation of fluorine into biologically active molecules because fluorine can improve bioactivity and pharmacokinetic properties [1]. Consequently, 22% of all small

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• ketones 93a–e for 4–8 hours in dichloromethane predominantly produced dimers 94a–e featuring a 1,2,4-trithiolane ring as the primary products, with yields ranging from 11% to 79% (Scheme 27). Spirodimers 94a–e demonstrated significant bioactivity against C. albicans (ATCC 10231) and S. cerevisiae (ATCC

• the spiro compounds showed similar activity to that of nystatin (2.46–4.86 mM vs 0.89–2.70 mM for nystatin). Based on the comparable antifungal activity observed between 108 and 109, the authors proposed that the oxathiaphospholane ring contributes to this bioactivity. Spiro steroids with six-membered

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

• to different peptide natural products. Although certain N-methylations may affect selectivity and bioactivity, a study on somatostatin derivatives showed that N-methylating the backbone improved oral bioavailability without affecting biological activity and selectivity [84]. α-N-Methyltransferases/N

• spectrum and loses all activity when unmethylated. Although the mode of action is unclear, the methylations are essential to the bioactivity. CypM methylates many oligopeptides that mimic the cypemycin N-terminal sequence, and unrelated peptide antibiotics. Additionally, CypM methylates short oligopeptides

• isolated from Bacillus amyloliquefaciens FZB42 and it mainly exhibits bactericidal activity against Bacillus anthracis [94][95][96]. The dimethylation is essential for its bioactivity; desmethyl plantazolicin showed MIC values >128 µg/mL for B. anthracis, while the dimethyl species showed MIC values

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• barriers to natural product discovery; high rediscovery rates, reliance on largely serendipitous response in bioactivity assays, and the resources and expertise required for their structure determination being the primary impediments [1][2]. With this background, accessing biological sources that have not

• synthesized and tested for antimicrobial activity. However, no clear trend was found between the ester length and bioactivity. In addition to the paraben derivatives, three known nucleosides, 4´,5´-didehydro-5´-deoxyinosine (18), 2´-O-methyladenosine (19), and 5´-methylthioinosine (20) were also identified

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• functional groups at C6 (Figure 4). The goals were to evaluate the scope of electrophile-mediated cyclization and diversify the gersemiane skeleton for bioactivity assays. A structural similarity search of 5 and 6 revealed that several natural products, including the coral gersemiols [24] and plagicosin N

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• , Indiana 47906, United States 10.3762/bjoc.20.88 Abstract Natural products (NPs) are fantastic sources of inspiration for novel pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, NPs containing furan moieties show activity against a variety of diseases

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• the first one, based on the known bioactivity displayed by bis(indolyl)methane (BIM) compounds, they reported the Pd-catalyzed carbonylative synthesis of the target compounds from aryl iodides and N-substituted and NH-free indoles in the presence of TFBen as the CO source [75]. A wide range of bis

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pristinamycin I NRPS. This TE domain showed activity for hydroxy groups and amines to form either lactone or lactam, and the broad substrate scope made this strategy potent for modifying the bioactivity of streptogramin antibiotics. In 2007, the same laboratory identified the interactive TE domain of the

• , resulting in daptomycin (12) formation with a ratio of cyclization to hydrolysis of 3:1 (Scheme 4a). The significance of single amino acids for daptomycin bioactivity was evaluated, for instance, the substitution of ʟ-3-MeGlu12 by ʟ-Glu12 in Dap yielded a 7-fold increase of the MIC against B. subtilis