Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• are versatile reagents that exhibit a range of reactions, both in the presence and absence of metal catalysts. In this study, we developed efficient synthetic methods for the preparation of aryl(TMP)iodonium(III) carboxylates, by reaction of (diacetoxyiodo)arenes or iodosoarenes with 1,3,5

• , consequently yielding the desired products in high yields. However, the common synthetic methods of diaryliodonium(III) triflates involving a strong oxidizing agent with a strong acid and an electron-rich arene often resulted in black/discolored products, indicating decomposition, poor yields, and lower

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• and guest molecules will give insight into a new class of developing methods of molecular magnets. XPS spectra for ACFs and FeCp2-ACFs-150. Peaks without labels originate from the indium substrate used for mounting the samples. The base lines of the spectra are shifted vertically from each other for

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

• supernatant. There are two main types of molecular probes based on their detection methods: imaging and UV–vis (Figure 2A). An imaging probe contains a mass spectrometry (MS) tag, oftentimes a halogen with a distinct isotopic ratio such as chlorine or bromine. A UV–vis probe contains a UV-tag, such as an

• Supporting Information File 10: Experimental materials and methods, supplemental figures, and supplemental spectra. Acknowledgements This work was supported in part by the Research Instrumentation Center in the Department of Chemistry at Purdue University. We thank G. Challis (University of Warwick), L

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

• relevant intermediates in organic synthesis [52][53]. Therefore, the significance of 6H-isoindolo[2,1-a]indol-6-ones has led to a longstanding interest in the development of efficient and versatile methods for their synthesis. In 2016, four independent studies reported the first successful application of a

• , the Li’s group and Zeng and Alper developed two different methods for carrying out a direct carbonylation of indoles with alkynes. Li’s group reported the direct Sonogashira carbonylation coupling reaction of indoles and alkynes catalyzed by Pd/CuI in the presence of iodine as oxidant [71]. The

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• . It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods. Keywords: building blocks; green chemistry; multicomponent reaction; Passerini tetrazole reaction; tetrazole; Ugi reaction; Introduction The

• . During preclinical research large screening libraries are integral part of the structure-based drug design and high-throughput screening and facile, efficient synthetic methods to explore diverse chemical spaces are of great help [2][3][4]. However, due to the vastness of chemical space, generation of

• the high synthetic value, significant efforts have been devoted to developing methods for the preparation of the tetrazole scaffolds, in particular recently through multicomponent reactions (MCRs) and mostly Ugi and Passerini reactions [7][8][9]. Traditionally, due to its charged nature the tetrazole

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• scientists. The Privateer software is a validation and analysis tool that provides access to a number of metrics and links to external experimental resources, allowing users to evaluate structures using carbohydrate-specific methods. Here, we present the Privateer database, a free resource that aims to

• intensities or amplitudes); each entry includes a re-refined, sometimes even re-built to some extent, copy of the original model. These newer versions are produced with state-of-the-art methods, many of which were probably not available at the time of deposition; hence, the quality of the models is expected

• to improve. Because the methodology included in PDB-REDO had been affected by the lack of automatic support that plagued general purpose crystallographic model building and refinement software [4], carbohydrate-specific methods have been gradually introduced over the years [22][23]. Whilst Privateer

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• studied due to the easy accessibility of fluoride ions with many methods directly employing the parent carboxylic acid as substrate. These processes avoid an additional pre-functionalisation step and have been reported using a range of deoxyfluorinating reagents including (diethylamino)sulfur trifluoride

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• a targeted enzyme [21][22][23]. One of these focus areas was the synthesis of alkyne-linked derivatives. The first alkyne-linked compound was already published in 1976, accompanied by new synthesis methods in the following years [24][25][26][27]. With the discovery of potential antiviral properties

• and other synthetic opportunities, alkyne-linked derivatives remained an integral part of research to the present day [28][29][30][31][32][33][34][35]. However, the main methods known so far are to substitute uracil either only at position 6 or at position 5 [26][27][28][34][35][36][37][38][39][40][41

• ][42][43][44][45][46][47]. The remaining known methods use only both positions to induce cyclization [25][31][32][33][48][49][50][51][52][53][54][55][56]. Therefore, to the best of our knowledge, there are no known methods that allow the selective reaction of both positions of uracil (Figure 2). In

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• natural products and pharmaceutical agents, including antifungal drugs [1][2][3], and hence their selective preparation has attracted considerable attention from the synthetic community. Compared to methods for the de novo construction of azole heterocycles, direct functionalization of the azole N–H bond

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

• substituents. It is therefore unsurprising that the number of methods seeking to access these has increased in recent times. In 2022 Brown and co-workers reported a strain release [2π + 2σ] cycloaddition induced by triplet energy transfer for the synthesis of 1,2,4-BCHs and 1,2,5-BCHs [38]. Some earlier

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• : Materials, synthetic methods, and copies of NMR spectra for all compounds. Supporting Information File 20: Crystallographic information file of compound 13. Funding We are grateful to the National Natural Science Foundation of China (No. 81973197, 81991525, 22107008), Beijing Natural Science Foundation (No

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• activated alkenes, extending this tolerance to the polar hydrochlorination of terminal alkenes remains a challenge. Metal-catalyzed radical hydrochlorination reactions have emerged as a practical solution, providing a versatile approach to hydrochlorinate a wide range of alkenes. Methods such as ours

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• identified. These as yet undiscovered secondary metabolite biosynthesis genes are called “silent genes”, because they are either not expressed or their expression levels are low under normal culture conditions. A number of studies have reported methods to activate these genes, and many new compounds have

• been discovered. In this review, we outline the silent gene activation methods, including the authors’ efforts (Figure 1). Review Artificial methods Several target-oriented methods focusing on specific biosynthetic genes and regulatory factors and artificial methods have been reported to activate

• the tetR regulator have been reported in several studies as methods to improve target-substance production capacity. Interestingly, Wilbanks et al. reported the structure–activity relationships of bacterial hormones in secondary metabolite biosynthesis by diversifiable synthesis [41]. The ability to

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• roots of plants. The content varies significantly among different plant species and different parts within the same plant. For instance, in C. sativus, crocins are predominantly accumulated in the stigma, but in G. jasminoides, they are primarily stored in the pulp. The traditional methods for

• extracting crocins include ultrasound-assisted extraction (UAE), supercritical fluid extraction, enzyme-linked extraction, and microwave-assisted extraction. Among these methods, the UAE exhibits a higher extraction yield [23][24]. Recently, Fiorito et al. developed a technique that utilizes cost-effective

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• cooperate with the PKS “in trans” [11][12]. Notably, in B. subtilis the giant bacillaene biosynthesis machinery forms an organelle-like complex that can be observed through cryoelectron microscopy [13]. The structure elucidation of “bacillaene” through extensive NMR spectroscopic methods revealed the

• is still important. Previous approaches to determine KS domain specificities have involved mass spectrometry (MS)-based methods [22][23], MS analysis of trypsin-digested proteins [24], and radiochemical assays [25]. Here, we report on a new method using 13C-labelled substrate surrogates in

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

• requires effective and economical preparation methods [5]. In the synthesis of these natural products and their analogs, macrocyclization through linear precursors, the key step in the general routes, was typically accomplished via conventional chemical methodologies [6][7], keeps presenting an obstacle

• increase the ratio of intramolecular nucleophilic attack, resulting in macrocyclic products via preorganization of substrate and enzyme in an active conformation [17][18]. Chemoenzymatic strategies, which merge practical enzymatic transformations with modern organic synthetic methods to increase the

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• azido-hydration reaction [18]. The homopropargylic azide was obtained in only 28% yield using phenyl vinyl ketone. Based on reported aza-alkynylation reactions [19][20][21][22][23] and modern azidation methods using radical chemistry [17][24][25][26] three approaches could be envisaged. All of them

• Temperature screening.a Additive screening. Fine-tuning of the reaction conditions. Supporting Information Supporting Information File 68: General methods, photochemistry set-up, reaction optimization, experimental procedures and compounds characterization. Funding The authors thank the Ecole Polytechnique

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• techniques employing transition-metal and photocatalysis [15][16]. These methods facilitate C–C bond formation, enabling the introduction of alkyl groups at the C2 position of quinazoline derivatives. While arylsulfanyl group rearrangement reactions have been documented by us for modifying 2,4-substituted

• 12a, diazide 13, and hydrolysis product 9 [25] which were inseparable using common purification methods (Table 1). The pivotal advancement occurred when attempting the reaction in DMSO (Table 1). In the case of 8a (R = 4-CH3C6H4), the product precipitated out when full conversion was reached

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• synthetic methods for γ- and ε-AA derivatives is much lower than those of α-AA derivatives [13][14]. Although synthetic strategies of γ- and ε-AA derivatives have been developed [15][16][17][18][19][20], acquiring complex γ- and ε-AA derivatives with simple starting materials in a one-step reaction remains

• a challenge. In addition, many studies show that unsaturated AAs exhibit a variety of unique biological activities [21][22][23][24]. Accordingly, the development of efficient methods to synthesize unsaturated γ- and ε-AA derivatives is a highly sought-after target to enrich non-natural AA chemistry

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• clusters (BGCs), several methods can be utilized, for instance, epigenetic regulation, co-culture, precursor feeding, heterologous expression, and changing fermentation parameters [11][12][13][14]. In the present study, we focused on a newly identified Penicillium strain, Penicillium shentong XL-F41. To

• found in the methods section. Chemical structures of compounds 1–12. Key 2D NMR correlations of compounds 1–3. Experimental and calculated ECD spectra at the CAM-B3LYP/6-311G(d,p) level of theory for compound 1. Biosynthetic exploration of compounds 1 and 2. A: The schematic presents the biosynthetic

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• multitarget drugs against COVID-19 [36], and amiaspochalasin C isolated from the solid culture of Aspergillus micronesiensis [37] and 1,9-epoxy-9a-hydroxystenine from the roots of Stemona tuberosa [38]) (Figure 1). Hence, the development of novel synthetic methods to construct spiro O-heterocycles constitutes

• procedures, analytical data and NMR spectra for the reported compounds. Acknowledgements We thank the Research Center for Magnetic Resonance, the Center for Chemical Analysis and Materials Research, and the Center for X-ray Diffraction Methods of Saint Petersburg State University Research Park for obtaining

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• were isolated preparatively and fully characterized by IR, 1H, and 13C NMR spectroscopy as well as HRMS and XRD methods. The reverse thermal reaction was catalyzed by protonic acids. N-Acylated compounds exclusively with Fe2+ formed nonfluorescent complexes with a contrast naked-eye effect: a color

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• ). Correspondingly, [1,3]thiazolo[4,5-b]pyridine 5 remained unchanged upon application of methods that had been successfully utilized in the hydrogenation of 1,3-benzothiazoles, involving diboronic acid or hydrazine hydrate as key reagents [21] in protic solvents at an elevated temperature (Table 1, entries 3 and 4

• ]pyridines that showed promising inhibition of the plant-specific enzyme FAT, we explored the selective late-stage conversion into the corresponding 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines via different reduction methods. Noteworthy, substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines had remained almost

• LEMPA. Supporting Information Supporting Information File 18: General synthetic procedures, characterization of all target compounds, methods for biological and biochemical testing, and scans of 1H and 13C NMR spectra of the new 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines. Acknowledgements We would like

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

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Since the seminal 1998 report by Teles et al. on the gold(I)-catalyzed addition of alcohols to alkynes [1], a multitude of gold-catalyzed reactions have been reported. Great successes in mechanistic analysis and synthetic methods have been achieved for allene and alkyne activation, while the activation

• catalyzed by triflic acid and the gold π-activation pathway was questioned [26]. Nevertheless, advancements in gold-catalyzed reactions continued to be achieved. In particular, successful asymmetric methods were reported in short time after initially reported non-asymmetric methods, specifically Kojima’s