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

• used, the reaction proceeded well with 78% conversion when monitored by both MS and NMR spectroscopy. However, when sodium chloride was used instead of sodium hydroxide, no conversion was observed. Temperature was also taken into consideration; temperatures above 55 °C were not considered because we

• minimal to no side products were observed via MS or NMR, thus validating the use of starting material for quantification. From this data, a few generalized conclusions can be drawn. Overall, the substrates with higher conversions were 14 and 16, which is in line with our hypothesis that having an electron

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

• determined by 1H NMR spectroscopy (Scheme 15). More recently, in 2016, still in Söderberg’s group, the synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, and indolo[2,3-b]indoles via reductive cyclization Pd-catalyzed was developed [36]. The reaction was possible

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

• 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

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• data for the new compounds. Acknowledgements We acknowledge the Ph.D. student Otto Daolio Köster for the fruitful discussions and assistance with the experimental work, and Mr. Anderson S. Pedrosa for technical assistance with NMR analysis. Funding We thank the financial support of the São Paulo

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

• equiv of NaH in DCM under conditions similar to our previous reports on the deoxygenative trifluoromethylthiolation of carboxylic acids [31]. 19F NMR analysis of the crude reaction mixture after 2 h at rt revealed no conversion towards the desired acyl fluoride product 2a, however, 30% of thioester 3a

• was formed (internal standard: PhCF3, Table 1, entry 1). Pleasingly, changing the base to K2CO3 led to the formation of 2a in 7% 19F NMR yield (Table 1, entry 2), while the selectivity of the reaction could be switched significantly upon employing organic amine bases (Table 1, entries 3 and 4). Using

• 2.0 equiv of diisopropylethylamine (DIPEA), 2a could be obtained in quantitative 19F NMR yield although a reduction to 1.5 equiv led to a significant drop in efficiency, delivering the acyl fluoride in only 30% 19F NMR yield together with 45% of thioester 3a (Table 1, entries 4 and 5). At this stage

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• and 13C NMR, and HRMS analysis. In addition, single crystals of compound 6d and 8c were obtained for X-ray analysis to confirm the structures (Figure 2). Conclusion In conclusion, we have developed a one-pot synthesis with two or three steps for making tetrazolo-pyrazino[2,1-a]isoquinolin-6(5H)-ones

• by NMR. General procedure for the Heck reaction; synthesis of product 6a A mixture of Ugi-azide adduct 5a (1 mmol), Pd(OAc)2 (0.1 mmol), PPh3 (0.2 mmol), K2CO3 (2 mmol) or NaOAc (2 mmol) in MeCN (3 mL) was stirred at 105 °C for 3 h under nitrogen atmosphere. After aqueous work-up, the crude product

• , and copies of NMR spectra. Supporting Information File 31: Crystallographic information file for compound 6d. Supporting Information File 32: Crystallographic information file for compound 8c. Acknowledgements We acknowledge Shaodong Jiang’s early work on this project.

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

• gives first insights into the optical properties. It was observed that the photophysical properties could be partially modulated by the chosen substituents. Experimental General information Nuclear magnetic resonance spectra (1H/13C/19F NMR) were recorded on a Bruker AVANCE 300 III, 250II, or 500. The

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

• oxazolidinone-substituted ynamide also proved to undergo iodo(III)azolation in a regio- and stereoselective fashion to give the product 4ai in a moderate yield. Note that terminal alkynes such as phenylacetylene also took part in the reaction, albeit in a much-diminished yield (7% by 1H NMR; data not shown

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

• to cyclopentane skeleton, as well as its stereochemistry, was originally elucidated as 1' as shown in Figure 1, on the basis of detailed analysis of 1D and 2D NMR spectroscopy. Spiroviolene was also found to be produced by several bacterial strains harboring SvS homologs [6][7], as well as putative

• detailed analysis of the NMR spectra, we have found that besides the normal hydroboration/oxidation product 1α-hydroxyspiroviolane (9), 9α- (10) and 9β-hydroxyspiroviolane (11) resulting from a formal boration at the homoallylic C9 position were also produced. The stereochemistry of the newly generated

• : 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

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• reaction was performed in the presence of 10 mol % Cu(OTf)2 and 1.0 equivalent of K2CO3 in DCE at a temperature of 80 °C. To our delight, the reaction afforded 3,4-benzocoumarin 3aa in a 27% yield (Table 1, entry 1). The structure of 3aa was confirmed through NMR spectroscopy and mass spectra analysis

• isolated as stable solids, whose structures were fully characterized by NMR spectroscopy. As shown in Table 3, we utilized 2-naphthol and 1-naphthol as template substrates to react with various unsymmetrical 2-ester-substituted diaryliodonium salts. Remarkably, iodonium salts 2 proved to be versatile in

• and characterization data of all products, copies of 1H, 13C, 19F NMR spectra of all compounds. Acknowledgements The authors thank the Research Center of Analysis and Test of the East China University of Science and Technology for the help on the characterization and Professor Zhen-Jiang Xu from SIOC

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

• , with the exo-hemiacetals favoured due to steric interactions between the substituents and alcohol, while the attempted preparation of 12b led only to complex mixtures (Scheme 2). The products of the reactions were characterised by 1D and 2D NMR, and X-ray crystallography of members from each class was

• used to confirm assignments. In the 1H NMR spectra of the chlorides 11a–f, a downfield shift for the anomeric methine was observed to δ ≈6 ppm from δ ≈5.4 ppm in the starting materials 10a–f. There was also a characteristic change in the appearance of the oxymethylene bridge spin system, with the

• products exhibiting much larger differences in the chemical shifts for the geminal protons relative to those observed in the starting material. For example, in the 1H NMR spectrum of 11e, the H4/H4′ resonances have a difference of 0.94 ppm, while in 10e, the progenitor H7/H7′ methylene resonances are

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

• mainly elucidated through comparative 1H and 13C NMR spectra and by comparing analytical data with existing literature reports [28][29] (see Supporting Information File 1, Figures S1–S7). The 1H NMR spectrum of compound 2 exhibited characteristic signals for one olefinic proton at δH (5.48) and four

• methyl groups at δH (0.83, 0.87, 0.98 and 1.77). Its 13C and DEPT NMR spectra showed 15 carbon resonances, including four methyl groups, four methylenes, four methines, and three quaternary carbon atoms. This information suggests that it may be a drimenol congener and the structure was further supported

• by comparison of analytical data with a literature report [29]. The 1H NMR spectrum of compound 3 is similar to that of 2, showing four methyl groups and one olefinic methyl singlet, indicating structural resemblances with minor variations. It was ultimately determined through literature comparison

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• ) is limited to reactive alkenes but provides very high yields (yields marked with an asterisk are NMR yields). The addition of DCl was also demonstrated by the use of D2SO4 instead of H2SO4. Not surprisingly, as already discussed in section "Reactions with HCl gas", higher pressures of HCl gas gave

• the reactivity of the corresponding alkene towards hydrochlorination. Normal temperature dependence for the hydrochlorination of (Z)-but-2-ene. Pentane slows down the hydrochlorination of 11. Ex situ-generated HCl gas and in situ application for the hydrochlorination of activated alkenes (* = NMR

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

• most other solvents. C60–oligo-Lys and C60–oligo-Glu were characterized by 1H and 13C NMR. Photoinduced 1O2 generation was observed in the most soluble C60–oligo-Lys conjugate under visible light irradiation (527 nm) to show the potential of this highly water-soluble molecule in biological systems, for

• . Additionally, 5a exhibited broad absorption in the visible region with relatively low intensity as well as a distinctive sharp peak at around 430 nm [48]. However, those features were not observed in the spectrum of C60–oligo-Glu (5b), presumably due to the aggregation [32]. The 1H NMR spectrum of C60–oligo

• part (α, β, γ, δ, and ε). The observed splitting of the protons a and b was presumably due to a diastereotopic effect of the methine proton c, similar to the spectrum of the monoadduct. Figure 6a shows the 13C NMR spectra of 5a in D2O and of the monoadduct in CDCl3. Together with the 1H NMR, COSY, HSQC

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

• carborane A3B-porphyrin were also synthesized based on the amino-substituted A3B-porphyrin. The structures of the prepared carboranylporphyrins were determined by UV–vis, IR, 1H, 19F, 11B NMR spectroscopic data and MALDI mass spectrometry. Keywords: bioconjugation; carboranes; fluorine; porphyrin; SNAr

• azide substituent in porphyrin 2 with SnCl2·2H2O in MeOH resulted in the formation of porphyrin amino-derivative 3 in 82% yield (Scheme 1). The molecular structures of compounds 2 and 3 were confirmed by a combination of NMR spectroscopy and mass spectrometry. Having synthesized porphyrins 2 and 3 we

• easily converted into hydrophilic charged entities by the protonation of the unsubstituted amino functionalities in their structure providing improved bioconjugation. Spectroscopic data All porphyrin conjugates were structurally characterized by IR, UV–vis, NMR spectroscopy, and mass spectrometry. The IR

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

• glutamate decarboxylase, and incubated with BaeJ-KS2. Substrate binding was demonstrated through 13C NMR analysis of the products against the background of various control experiments. Keywords: bacillaene; biosynthesis; enzyme mechanisms; isotopes; trans-AT polyketide synthases; Introduction Polyketides

• 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

• by the preceding modules (highlighted in purple) [14][16]. Furthermore, the structures of 1 and 2 show a shifted triene portion that is not in conjugation with the carboxylic acid function. NMR studies of off-loaded intermediates with the TE deletion mutant revealed that these double bond shifts are

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• HREIMS spectrum. The 1H and 13C NMR spectra of 1 were identical to those of sandaracopimaradiene [30][31]. As the specific rotation of compound 1 was in good agreement with the reported data ([α]D24 −14.3 (c 0.97, CHCl3) in this study; [α]D25 −10.29 (c 0.65, CHCl3) in the literature [31]), compound 1 was

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

• under blue light irradiation afforded 4a in 17% NMR yield (Table 2, entry 1). The major byproduct formed during the transformation was identified as diazide 6. When a copper photocatalyst is involved, a lot of diazidation can be observed. We assumed it could be caused by the reaction of Ts-ABZ (3) with

• transformation before [41][42][44], in our case only 9% of the desired product was obtained (Table 3, entry 2). A large quantity of product resulting from a Ritter-type reaction between acetonitrile and the carbocation intermediate could be observed by NMR [55]. Other highly polar solvents such as DMF and DMSO

• diasteroisomer was determined to be trans. Diyne 4l could be accessed in 44% yield from the exclusive 1,2-functionalization of the corresponding ene-yne. Crude NMR of the reaction did not show the presence of an allene product which could have been formed by a 1,4-functionalization. Enol ether could also be

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• iron cycle within the rhizosphere. This study focused on exploring the natural products of the soil-isolated Variovorax sp. H002, leading to the isolation of variochelins A–E (1–5), a series of lipohexapeptide siderophores. NMR and MS/MS analyses revealed that these siderophores share a common core

• this study, we isolated three new congeners of variochelin-type siderophores, variochelins C–E (3–5), along with two known compounds, variochelins A (1) and B (2), from Variovorax sp. Their structures were elucidated by a combination of NMR, ESIMS/MS, and chemical derivatization. The analysis of the

• showed a molecular weight of m/z 535.7912 for the [M − 2H]2− ion, inferring a chemical formula of C47H83O17N11 (calcd 535.7911 for the double-negative ion). A combination of 1H NMR and COSY analyses revealed a peptidic structure comprising two Nδ-acetyl-Nδ-hydroxyornithine residues, a proline (Pro), a

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• catalysed by copper(II) complex of ligand IV. Asymmetric aldol reactions of various aldehydes with ketones catalysed by compound IV. Supporting Information Supporting Information File 62: General information and experimental data of prepared compounds, copies of 1H and 13C NMR spectra and DFT calculations

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

• azide–tetrazole equilibrium of product 12a was initiated, revealing a singular form present in all solvents. Despite attempts to increase the amount of the azide form with the increase of the temperature in NMR experiments [27], no observable alteration in the tautomeric equilibrium was observed. FTIR

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

• temperature (rt), the desired unsaturated ε-AA derivative 4a was obtained in 75% isolated yield (Table 1, entry 1). Isolation and NMR analysis demonstrated that this model reaction provided amino acid 4a with good E-selectivity and excellent regioselectivity (E/Z = 91:9, 1,4-/1,2-addition >20:1). Control

• Supporting Information File 1. Optimization of conditions and control experiments.a Supporting Information Supporting Information File 54: Full experimental details, analytical data and NMR spetra. Funding Financial support from the National Natural Science Foundation of China

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

• by the higher HOMO level of 3 compared to that of 4. The products were characterized by spectroscopic and spectrometric analyses (Figures S3–S11 in Supporting Information File 1). 1H, and 13C NMR spectra clearly indicated the formation of [2 + 2] monoadducts. 7Li NMR spectra showed a sharp singlet

• , only the E-isomer was observed, as confirmed by 1H-1H 2D-NOESY NMR spectrum (Figure 4). This is not surprising because similar stereoselectivity has been reported in the photoinduced [2 + 2] cycloaddition reaction of empty C60, where the E-isomer is most thermodynamically stable [19][22]. The positive

• Corp., TCI, Sigma-Aldrich) and used as received without further purification. Li+@C60TFSI− was purchased as PF6− salt from Idea International Corp., and then its counter anion was exchanged to TFSI− according to reported procedures [9]. NMR spectra were recorded on a JEOL JNM-ECZ400S (1H: 400 MHz, 7Li

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• from a marine Okeania sp. cyanobacterium. The relative configuration was elucidated primarily by analyzing the two dimensional nuclear magnetism resonance (2D NMR) data. The absolute configuration was clarified by comparing the electronic circular dichroism (ECD) data of 1 with those of known analogs

• characteristic UV absorption around 270 nm. The molecular formula of 1 was determined to be C44H66O15 based on the HRESIMS data. The NMR data for 1 are summarized in Table 1. The 1H NMR spectrum of compound 1 was similar to those of known polycavernosides but matched none of them, suggesting that 1 was a new

• analog of polycavernosides [1][3][4][5]. A detailed analysis of the NMR data revealed the planar structure of 1, as shown in Figure 2. COSY and HMQC spectral analyses revealed several partial structures, indicated by the bold bonds in Figure 2. Four HMBC were observed from singlet methyl signals: δH 0.85

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• ). After large-scale cultivation, 3 was isolated and subjected to nuclear magnetic resonance (NMR) analysis, which suggested that 3 is the C-5′ desmethyl form of preterretonin A [17]. However, several missing signals in the 13C NMR spectrum, likely due to keto–enol tautomerization in the D-ring, hindered

• -5′ desmethyl form of the product from the K187A variant of AdrI, which was created during the in-depth functional analysis of terpene cyclases involved in DMOA-derived meroterpenoid biosynthesis [21], through NMR and single-crystal X-ray crystallographic analyses (Figure 2C and Figure S1 in

• . Finally, the A. oryzae strain expressing insA7 produced two major metabolites 7 and 8. Compound 7 was determined to be the C-5′ desmethyl form of insuetusin A1 [19] using NMR and single-crystal X-ray diffraction analyses (Figure 2C and Figure S1 in Supporting Information File 1; CCDC: 2300695) and was