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

• . Sashidhara et al. reported no conversion, while Liu et al. reported a 58% yield of the GBB product, postulating the ability of ethylene glycol to function as an activator (through hydrogen bonding) and a facilitator of proton transfer. After this discovery, ethylene glycol has never been employed in GBB

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• properties as a function of the number of building blocks of each type (from 1–4; the number of examples containing more than 4 building blocks of a single type are too few to be statistically meaningful). Not surprisingly, the trends shown in Figure 10 reiterate and further substantiate some of the previous

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

• function–structure relationships and how they impact biological activity. Since we have not found evidence of horizontal transfer of the cloA1 and cloA2 gene clusters, it is an interesting speculation that they could constitute the origin of this family and that, by duplicating one of these clusters, C

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

• epoxide was then opened by treatment with sodium azide and boric acid, yielding the azide derivative 146 in 87% from estrone. A subsequent reduction of the azide with LiAlH4 provided the aminoalcohol derivative 147 in 64% yield. Then, a chloroacetamido moiety was formed at the amino function in 51% yield

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

• substrate–enzyme combinations. The integrative approach of combining intriguing enzymes in ever-evolving biosynthetic research with chemical synthesis, would foster collaborative breakthroughs in the interdisciplinary landscape of natural product biosynthesis, total synthesis as well as function- and

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• different python scripts (provided in Supporting Information File 1). The rate equations are ordinary differential equations (ODEs) and can thus be solved numerically using existing methods in the SciPy package [50]. An absorbance function was constructed, which takes the solution of the ODEs to model the

• absorbance over time. This absorbance function was then fitted to the measured absorbance at the wavelength of irradiation (or wavelengths, for a non-monochromatic excitation light). The parameters ΦA→B and ΦB→A were evaluated to minimize the residual sum of squares (RSS) between the measured and fitted

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

• peptides at the C-terminal carboxy group of different amino acids, namely methionine, isoleucine, and valine. This demonstrates its tolerance to various substrates. LahSB does not require the leader peptide or other modifying enzymes to carry out its function [72], making it a promising tool for

• biocatalytic applications. The co-crystallisation of LahSB with bound SAH provides important details about the structure–function relationship, the substrate–enzyme interaction, and the cofactor binding site (Figure 5). This structural information, including the residues involved in binding, is essential for

• enzyme engineering and rational design [73][74]. Lentzea kentuckyensis sp. produces lassomycin (Figure 4), a lasso peptide, with a methyl ester at the C-terminus. The las cluster encodes LasF, which is predicted to function as an O-MT. Since no other putative MT is encoded in the las cluster, LasF is

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

• domain. It functions as an exochitinase. The two catalytic domains have different activities on chitooligosaccharides. Each domain was maximally active from 30 °C to 37 °C and from pH 7.2 to 8.0. Both domains function cooperatively to degrade chitin [22]. It should be noted that M. degradans 2-40 was

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• classifier as Ree et al. [14] have shown the opposite to be true for electrophilic aromatic substitutions. However, our regression model serves a dual function, that is, it accurately predicts pKa values and identifies the reaction site. Prediction of aryl C–H borylation sites In the previous section, we

• , respectively, when correlating with QM-computed pKa values. Both methods are freely available under the MIT license. Our workflow can function as a filtering tool for computer-aided synthesis planning for the synthesis of various pKa-dependent reactions (aldol, Michael, and Claisen), evidenced by its accurate

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• . Single-point calculations were improved using a mixed basis set of triple-ζ quality with a polarization function, 6-311G(d,p) for all atoms except for Br and I, which were treated with the LANL08d relativistic pseudopotential [41][42][43], i.e., the composite level of theory used is the following: (SMD

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• (Figure 1). Recent enzymatic reconstitution has demonstrated that the burpitide cyclases can function either autocatalytically (fused) or as traditional stand-alone proteins with separate free peptide substrates (split) [4][7][8][9][10][11]. When fully matured, burpitides possess a wide range of

• containing cores matching known molecules such as hibispeptins, moroidins, jubanines, and lyciumins were selected for the new model (see Supporting Information). The sequences were aligned and the hmm build function of HMMER v3.3.2 was used to generate the model [36]. The HMM is available in Supporting

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• their function is three-fold; as a fluoride source, as a supporting electrolyte and as a proton source, allowing for the hydrogen-evolution reaction as the counter electrode process [91]. Benzylic fluorination with these reagents has been observed as a side-product in the electrochemical generation of

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• Yukang Wang Yan Yao Niankai Fu Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China 10.3762/bjoc

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• deactivation of biological function. It also offers the potential to change the properties of defined molecules in biological systems with minimal disturbance to the rest of the system. Photoswitchable ligands, i.e., the incorporation of light-responsive moieties into a drug-like molecular structure, allow

• has a tetrameric structure, displays a high affinity for ᴅ-galactose (ᴅ-Gal, with Kd = 34 μM) and galactosides. The 3- and 4-hydroxy function on the ᴅ-Gal unit are involved in the coordination of Ca2+ in the binding site [5][6][7][8][32]. A large range of galactosyl conjugates have been synthetized

• total heat released as a function of total ligand concentration for the titration shown in the upper panel. The solid line represents the best least-square fit to experimental data using a one site model. (A) Enthalpy–entropy compensation plot of compounds 1–5 from ITC analysis. The dotted green line

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• ) Sequence alignment of KR domains whose stereoselectivity cannot be predicted based on the reported motifs. The labels show the product name and the order of the module where KR is located in the PKS assembly line (starting from the module with condensation function). KR types predicted based on the

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• ), whose sequential acylation process by iso(thio)cyanates 3a–h gives rise to the asymmetric (thio)urea derivatives (intermediate II). The spontaneous nucleophilic attack of the (thio)amide nitrogen on the terminal methyl ester function at C-4 of the starting azo-ene system provides a regioselective

• keto function of the hydrazone moiety and the open-chain hemiacetal or aldehyde hydrate in Brønsted acid medium to access 1H-imidazo[5,1-c][1,4]oxazine derivatives (Scheme 1) [21]. Considering that the hydrazone function at C-4 of 4a–r may exist in a tautomeric equilibrium with the corresponding ene

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• developing novel inhibitors of integrin function, we identified a drug candidate (10n) through high throughput screening (HTS) that inhibits the integrin complex formation, which is an important step for integrin activation. The binding inhibitor 10n was effective as IC50 of 190 μM in AlphaScreen system, and

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• thorough photochemical characterization is essential for efficient light-driven applications. In this article, the mode of action of a polyazahelicene catalyst (Aza-H) was investigated using laser flash photolysis (LFP). The study revealed that the chromophore can function as a singlet-state photoredox

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• electrons over the adjacent carboxylate function, which prompted the selenation pathway, leading to the formation of two of the isomeric diorganyl selenides of methyl anthranilate. The diaryl selenides were structurally characterized using single-crystal X-ray diffraction. Density functional theory

• aniline with an electron-donating function (i.e., o-anisidine) undergo significant polymerization in the presence of SeO2, we were interested in studying this reaction using methyl anthranilate, having an electron-withdrawing group (Scheme 4). To our surprise, the quantity of polymer 3 formed was low

• . Conclusion Aniline and o-anisidine underwent a predominant oxidative polymerization reaction with SeO2. Therein, electrophilic selenation was poor. The reactivity of the NH2 unit towards oxidation could be partially suppressed by the presence of an electron-withdrawing function. Consequently, for methyl

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

• , Supporting Information File 1) [21][22]. In this study, we reveal the previously undisclosed facet that AlpJ-family oxygenases can function as cofactor-independent oxygenases when the hydroquinone intermediate CR1 (8) serves as the substrate. In this context, the enzymes autonomously catalyze oxidative C–C

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• with excellent properties as organic photovoltaic materials [9][10][11][12][13][14]. Furthermore, regioisomerically pure bis-functionalized fullerenes function better as electron acceptors in organic thin-film solar cells than mixtures of the corresponding regioisomers do [12][13][14]. Therefore

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• function in an organism, but the activities can also be detrimental. CDA is highly active in the liver and spleen, which results in deamination and consequent deactivation of several chemotherapeutic agents, including the anticancer agents cytarabine, gemcitabine and 5-aza-2'-deoxycytidine (decitabine) [2

• kinetic data using Lambert’s W function [71]. This method provides better estimates for the Michaelis–Menten constant (KM) and maximum velocity (Vmax) than nonlinear regression analysis of the initial rate (V0). It is also superior to any of the known linearised transformations of the Michaelis–Menten

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• us to try another protecting group for the formyl function, namely arylhydrazone. Thus, reactions of compounds 7a–c with a number of arylhydrazines afforded the corresponding hydrazones 11 which were not isolated and subjected to cyclization under the action of K2CO3 (Scheme 5). In most cases the

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• suitably decorated benzoxazole derivative 12a. The benzoxazole core showed increased sensitivity towards a basic environment, resulting in the ring-opened side product 13 through saponification of the ester function of compound 12a. The identification of this side product proved to be challenging due to

• insufficient evidence provided even by meticulous NMR analysis and eventually had to be confirmed by X-ray crystallography (Figure S1, Supporting Information File 1). Changing the ester function from an ethyl to an allyl group enabled a very mild cleavage using a Pd-mediated reaction with triethylsilane [28

• curves. C) The IC50 values were determined using the GraphPad algorithm (IC50 value of compound 1 was published by Dejmek et al. [24]), the BEI was calculated using the function pIC50 [mol/L]/MW [kDa]. Synthetic pathway to benzoxazole analogue 2 of HeE1-2Tyr (1). Reagents and conditions: a) TMSN3, TfOH

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 metal-catalyzed direct C–H carbonylation of indoles is an effective and straightforward approach to synthesize indole derivatives containing a carbonyl function in position 3. On the other hand, only a few examples to synthesize indole-2-carbonyl derivatives have been realized. One example is the