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

• details and copies of 1H, 13C, and 19F NMR spectra. Acknowledgements T.D. thanks for the generous gift of fluoroalcohols from Central Glass Co., Ltd. Funding N.T. and T.D. acknowledge support from JSPS KAKENHI Grant Number 20K06980 (N.T.) and 19K05466 (T.D.), JST CREST grant number JPMJCR20R1 (T.D.), and

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

• complexes are important for the synthesis of heterocyclic and non-heterocyclic compounds. In 2009, Arthuis and co-workers developed a new process for the synthesis of 2-aroylindoles and 2-heteroaroylindoles by a one-pot palladium-catalyzed domino reaction that involves an initial C,N-coupling followed by

• carbon monoxide insertion, and Suzuki–Miyaura coupling reaction, from 2-gem-dibromovinylaniline [12]. In the presence of Pd(PPh3)4 (5 mol %) as catalyst, 5 equivalents of base (K2CO3), an aryl- or heteroarylboronic ester (1.1 equivalents), CO (12 bar), in dioxane at 100 °C after 16 h the indole

• of amides from 2-alkynylanilines by using TFBen (benzene-1,3,5-triyl triformate) as a CO source, Pd(OAc)2, DPEPhos (bis[(2-diphenylphosphino)phenyl] ether), and DIPEA (N,N-diisopropylethylamine) in MeCN. After 24 h, Pd(OAc)2 and AlCl3 were added to promote a selective cyclization reaction [14]. 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

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

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

• . Combining water with different co-solvents such as MeOH, DCM, CH3CN and THF provided products generally with low to moderate yields of 29–69% (Table 1, entries 9–14). The low yield of the desired product is either due to the formation of 1-benzyl-1H-tetrazole as side product or low conversion and the oxo

• yield. Optimization of reaction conditions. Supporting Information Supporting Information File 8: Experimental procedures, compound characterizations, and NMR spectra. Acknowledgements We acknowledge the contribution from the Ph.D. thesis of co-author Jingyao Li, https://research.rug.nl/en

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

• formation of acyl fluorides 2. Alongside a fluoride ion, β-fluoride elimination from a (trifluoromethyl)thiolate (−SCF3) anion (C) also generates a thiocarbonyl difluoride species D. As previously demonstrated by Schoenebeck and co-workers in a deoxyfluorination of carboxylic acids with NMe4SCF3, this

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

• agents, preferably with well-defined stereochemistry, is a nontrivial task. The addition of azoles to alkynes represents an alternative approach to N-vinylazoles. For example, Nolan and co-workers recently reported a gold-catalyzed addition of azoles to alkynes (hydroazolation; Scheme 1b) [10]. The gold

• . Optimization of reaction conditions.a Supporting Information Supporting Information File 22: Experimental procedures and characterization data of new compounds. Acknowledgements We thank the Central Glass Co., Ltd. for the generous donation of 1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-ol (HFAB). Funding This

(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

• Baran, Collins and co-workers and Anderson and co-workers showed that the substituent distance d of 3.5–4.0 Å and substituent angle φ1 of 89° inhabit a chemical space between ortho- and meta-substituted benzene (Figure 2) [26][27]. The 67° dihedral angle θ between the substituents differs significantly

• from both compounds. The first investigation of 1,2-BCPs as an isosteric replacement for ortho-benzene was reported by Baran, Collins and co-workers [26]. They prepared a wide variety of 1,2-BCPs from a common 2-substituted [1.1.1]propellane building block, propellane 3a (Scheme 1A). Propellane 3a was

• . Bennet and co-workers also reported the synthesis of 1-amino-1,2-BCPs (±)-11a–e via a similar strategy (Scheme 1C) [29]. They were able to prepare differently-substituted [1.1.1]propellanes 3b–f and subject these to strain-release amination reactions. The synthesis was shown to tolerate typical alcohol

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

• proposing a reasonable cyclization mechanism [5]. Spiroviolene (1, Figure 1) was identified by Dickschat and co-workers as a nascent cyclization product of spiroviolene synthase (SvS), the coding gene of which was cloned from Streptomyces violens NRRL ISP-5597 [6]. Its unique spiro-fused linear triquinane

• from Fusarium graminearum GJ1012 [11], have been reported almost at the same time. The discrepancy of the stereochemistry at C3 between 1' and 2 was first noticed by Snyder and co-workers [12]. The conserved stereochemistry of spiroviolene and 2 at C3 was later confirmed by the conversion of a

• synthetic intermediate of 2 to spiroviolene. By taking advantage of the DFT transition state analysis of the hydroboration reaction of a key intermediate, as well as NOE correlation analysis of the resultant product, Snyder and co-workers have reassigned the right structure of spiroviolene to 1. However

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• -cleavage reactions and rearrangements when modified at the 4-position [15][16][17]. Baillargeon and Reddy first reported rearrangements of 6,8-dioxabicyclo[3.2.1]octane derivatives promoted by diethylaminosulfur trifluoride (DAST) [18], and later Karban and co-workers reported a migration of oxygen from

• ]octane, while O6 migrated when the C4–OH was axial leading to 2,4-dioxabicyclo[2.2.2]octanes. The formation of both anomers from the non-selective addition of fluoride suggested intermediates with oxocarbenium character. This work has recently been extended by Banwell and co-workers to include a set of

• the byproduct triphenylphosphine oxide, necessitating chromatography which resulted in some hydrolysis. There are a number of catalytic activation strategies for Appel or Mitsunobu reactions such as those described by the Denton group [30], and Rutjes and co-workers [31], and while these may prove

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

• SUKA22 DL10085. The DL10086 strain, with the deletion of the cavA gene, failed to produce 2 or 3, suggesting the vital role of cavA in cav BGC. To further substantiate the hypothesis, cavB and cavC were co-expressed with each of the three P450s in S. avermitilis SUKA22, creating three recombinant strains

• (DL10089, DL10090, and DL10091; Tables S3–S5 in Supporting Information File 1). Notably, the DL10089 strain, co-expressing drimenol synthase and CavA, successfully produced 2 and 3. This result not only corroborates our initial findings but also confirms the CavA role in hydroxylating the C-2 and C-3

• Streptomyces strains, with S. avermitilis SUKA22 harboring the empty pSET152 vector as the control. (d) HPLC analysis of metabolites co-expressed with drimenyl diphosphate synthases (CavC), Nudix hydrolase (CavB), and one of the P450s, either CavA (DL10089), CavE (DL10090), or CavG (DL10091). Substrate scope

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• focusing on hydrochlorination reactions. Firstly, an outstanding overview, including extensive research from the former Soviet Union, was reported in 1982 by Sergeev and co-workers [12]. Secondly, the chapter on “Addition of H-X Reagents to Alkenes and Alkynes” in comprehensive organic synthesis gives a

• great overview of hydrochlorinations which were reported between 1940–1980 [13]. Thirdly, Yang and co-workers presented a mini-review on recent hydrochlorinations in 2021 [14]. In this review, hydrochlorination reactions from 1990 to 2023 are comprehensively covered, including several earlier reports to

• ]. It is important to note that we are not aware of any catalytic enantioselective hydrochlorination reactions of alkenes. Conjugate additions of HCl to a complex of α,β-unsaturated acids, incorporated in an α-cyclodextrin, which corresponds to a formal hydrochlorination was reported by Tanaka and co

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• example, as a photosensitizer in photodynamic therapy. Keywords: biomaterial; fullerene; peptide; water-soluble; Introduction Since the seminal discovery in 1985 by Kroto, Smalley, Curl, and co-workers [1], fullerenes, specifically buckminsterfullerene C60, have intrigued the scientific community. The

• derivatives by covalently attaching water-soluble moieties to the fullerene core. Subsequently, Nakamura and co-workers further developed reactions between C60 and organocopper reagents, enabling the sequential addition of functional groups to obtain penta- and decaadducts, which largely enhanced the water

• solubility [14][15]. As early examples of the latter approach in the 1990s, Wennerström and co-workers reported the study of supramolecular BiCAP complexation of C60 with γ-cyclodextrin (γ-CD) [16]. Shinkai and co-workers synthesized water-soluble calixarene derivatives to form water-soluble complexes with

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

• , and the associated undiscovered secondary metabolite biosynthesis genes are called “silent” genes. This review outlines several approaches to further activate the metabolic potential of actinomycetes. Keywords: actinomycete; co-culture; heat shock metabolites (HSMs); secondary metabolites; silent

• Zeeck and co-workers in the early 2000s, is a method in which the target bacteria are cultured under various conditions (medium composition, temperature, pH, oxygen supply, light quality and quantity, addition of precursors and enzyme inhibitors, etc.) and all metabolites obtained from them are analyzed

• (34) [74], resistoflavin (35) [75], and tetracenomycin D (36) [76] were also identified as HSMs from Streptomyces sp. HN66. Carlson et al. reported the production of resistomycin by co-cultivating Streptomyces sp. B033 and Burkholderia vietnamiensis ATCC BAA-248 [77]. These results suggest that high

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

• thank all co-workers who contributed to this review. Funding This work was supported by the Natural Key Research and Development Program of China (2020YFA0907900) and the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine (22HHZYJC00004).

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

• -century [32][33][34][35]. Biosynthetically, the corresponding cluster consists of three NRPS, TycA-C, and at the C-terminus of TycC, the TE domain can catalyze a head-to-tail macrocyclization and deliver tyrocidines [30]. With a comprehensive understanding of its biosynthetic mechanism, Walsh and co

• strategy has been widely employed in the TE domains characterization and chemoenzymatic synthesis of other bioactive macrocyclic peptides, such as surfactin [40], streptogramin B [41], cereulide [42], seongsanamide E [43], etc. In 2005, Marahiel and co-workers accomplished the chemoenzymatic synthesis of

• cyclization process. Most recently, the synthesis of monocyclic depsipeptide, seongsanamide E (10), was reported by Boddy and co-workers via two different strategies [43]. On the one hand, the regular chemical approach, attempting Yonemitsu’s conditions to macrolactonize the seco-acid, was unsuccessful. On

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

• the development of the azidobenziodazolone scaffold [17]. This class of derivative showed an improved safety profile while retaining the redox properties of the original reagent. A single example of azido-alkynylation has been reported by Ramasastry and co-workers during a mechanistic study for an

• the increased yield with the addition of HFIP was not significant enough to compensate the downside of having an expensive co-solvent. Next, the stoichiometry of the different reaction components was examined. When styrene (1a) was used as limiting reagent instead of Ts-ABZ (3), a slightly higher

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

• be difficult to achieve using either radical or polar chemistry alone. In recent years, Gevorgyan, Glorius, Huang and their co-workers reported elegant examples of the carboamination of 1,3-dienes with unactivated alkyl halides and amines under photoinduced palladium catalysis via a radical-polar

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• University, which is a shared research environment, is also acknowledged. Funding This work was partly supported by Grants-in-Aid for Scientific Research (21H01737 to H. U.) from JSPS, Japan, and financial supports from Fukamatsugumi Co., Ltd., Sendai, Japan (to Endowed Research Laboratory of Dimensional

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• [20][21] that should facilitate access to different groups at the oxazole C-2 position allowing a range of imidazolium-forming cyclisation strategies to be explored. Glorius and co-workers reported the formation of symmetrical NHCs by imidazolium ring formation from bisoxazoline motifs [22] but

• method and Sambvca V.2.0 software (Scheme 2) [29]. Although a similar value to that reported for IPrAuCl (%Vbur = 45.4%) [30] the steric map shows a very different steric environment on either side of the ligand. The AImOxIr(CO)2Cl complex 15 was targeted in order to assess the electronic effects of the

• fused imidazolium core (Scheme 2). No reaction was observed between 6a and [Ir(cod)Cl]2 in the presence of NEt3. A solution of the free carbene was prepared from 6 and reacted with [Ir(cod)Cl]2 and then CO to afford the AImOxIr(CO)Cl complex 15. A minor side-product with a strong red colour was formed

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

• IMS Q-Tof liquid chromatograph mass spectrometer. For NMR analysis, we utilized an AVANCE II 600 spectrometer, referencing residual solvent peaks at δH/δC 7.27/77.0 ppm in CDCl3 for chemical shift calibration. We utilized commercial silica gel from Yantai Xinnuo New Material Technology Co., Ltd

• Co., Ltd, Yantai, China. Fungus isolation and characterization The fungus Penicillium shentong XL-F41 was isolated from soil collected in Shentong Mountain, Shandong Province, China, in June 2022. It was cultured on potato dextrose agar (PDA) at 28 °C. Sequencing and comparison with the GenBank

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

• binding affinity to enzyme targets, e.g., acyl-ACP thioesterases, belonging to the protein family of FATs, was demonstrated by using co-crystallization, fluorescence-based thermal shift assays, and chemoproteomics techniques [3]. Likewise, methiozolin (2) is a recently assigned FAT inhibitor that has

• lead structure with ample space for structural variations. By formally replacing one pyridine moiety of 1,8-naphthyridine 4 by a five-membered thiazole unit, we have identified thiazolo[4,5-b]pyridine 5 as a strong inhibitor of acyl-ACP thioesterase, which has further been confirmed via an X-ray co

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

• particularly evident for metal complexes, where the system's geometry can be finely tuned to modulate its response based on the selection of metal and ligand components. This aspect has been extensively explored by Schmittel and co-workers in a recent review [17]. Molecular tweezers have been developed in this

• achieved by chemical (hydroxide/proton) or electrochemical (reduction/oxidation) stimuli allowing the enrichment of perylene from a mixture of polycyclic aromatic hydrocarbons (PAHs) in phase-transfer experiments into a perfluorocarbon phase. Metal cation responsive tweezers In the early 2000s, Lehn and co

• the two metallic centers in the tweezers cavity in a bridging mode. For the heterometallic Zn/Au system, luminescence quenching was observed in the closed state. The pyridine-hydrazine-pyridine unit has been extensively studied by Lehn and co-workers in coordination-responsive supramolecular polymers

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• Island, Ou, Kumejima, Shimajiri District, Okinawa, Japan. Genomic DNA was prepared, and the 16S rRNA gene was amplified by PCR using the method of Inahashi and co-workers [23]. The sequencing analysis was performed by Eurofins Genomics. Similarity of 16S rRNA gene sequence was computed by using

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

• co-solvent, but the conditions were modified to use readily accessible commercial [JPhosAu(NCCH3)]SbF6 (5) and MeOH, since water posed miscibility problems at higher concentrations. Titrating increasing amounts of water into reactions with JPhosAuOTf (4d) led to an increase in rate, similar to that

• effect of MeOH co-solvent on the 1a → 3a transformation was due to its role as a hydrogen bonding donor (proton source), or due to its role as a hydrogen bonding acceptor (Lewis base) [44]. To this end, we examined the impact of different alcohols (varied acidity and polarity) and different non-protic

• , comparing intermolecular to intramolecular hydroamination, Widenhoefer and co-workers found opposite trends for efficient asymmetric induction: the intermolecular variant requires non-polar aromatic solvents while the intramolecular variant requires polar solvents [3]. Agbossou-Niedercorn, Michon, and co

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• lithium hexamethyldisilazane following a literature procedure reported by Liu and co-workers (see Supporting Information File 1) [44]. Subsequently, difluorinations of DBM substrates 1b–n were performed under conditions similar to those optimized for the preparation of 3a. The desired difluorinated

• estimated from pKa differences between acidic species and potential base species. The pKa(MeCN) for dibenzoylmethane (1a) can be estimated from pKa(DMSO) [50], where pKa(MeCN) = pKa(DMSO) + 12.9 = 13.4 + 12.9 = 26.3. Mayr and co-workers have shown the 2-fluoro-substituted species to be only slightly less