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

• complement the growing glycan content of the PDB. Keywords: carbohydrates; database; N-glycans; N-glycosylation; polysaccharides; validation; website; Introduction Carbohydrate modelling is an important but often cumbersome stage in the macromolecular X-ray structure solution workflow. The accurate

• entry in the PDB [24] or in PDB-REDO [21]. For each structure in the PDB, the carbohydrate-containing chains are first identified before being validated using the suite of validation tools available within Privateer. Using the Python bindings available within the latest versions of Privateer, a

• late Willy von der Lieth, pioneers of carbohydrate structure validation, whose research informed some of the methods showcased in the Privateer database. Funding Jordan Dialpuri is funded by the Biotechnology and Biological Sciences Research Council (BBSRC; grant No. BB/T0072221). Haroldas Bagdonas is

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

• intermediate. A second effect appears to play a more important role and could be related to the structure of the starting material. The 6-position is part of an enamine and an α,β-unsaturated carbonyl structure, as depicted in Scheme 3. According to the mesomeric structure of the enamine, the 6-position could

• ring instead of a benzene moiety. This was demonstrated by the introduction of thiophene (5r) and furan (5t) to the uracil structure. The molecules 5n and 5o could not be obtained, due to decomposition during the reaction. The structure of 5a was confirmed by X-ray crystallographic analysis. Crystals

• were obtained by slow evaporation of the solvent from a mixture of the compound in dichloromethane and heptane at room temperature (Figure 3). Crystal structure analysis revealed that 5a crystallizes in a base-centered monoclinic system with the P21/c space group. The structure is mostly planar, except

(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

• well as the impact they have on the physiochemical and biological properties of pharmaceuticals and agrochemicals. Keywords: bioisosteres; drug discovery; meta-benzene; ortho-benzene; Introduction The logical and iterative modification of the structure of a drug candidate is a critical part of the

• ]propellane (129). Gassman reported the initial synthesis of [3.1.1]propellane (129) in 1980 [61], and this was recently optimised by Uchiyama (Scheme 13A) [47]. Cyclisation to the bridged structure 126 was achieved by enolate formation and intramolecular nucleophilic substitution of iodide diester 125. A

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

• 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

• IM-7. A key 1,3-hydride shift of IM-7 from the β-face, followed by deprotonation of the formed C2-cation IM-8, would deliver the originally proposed structure 1' [6]. However, no related natural products that would be derived from the intermediates of this pathway have been found so far. A third

• suitable for X-ray diffraction [35]. The crystal structure of 13 clearly showed that the 19- and 20-methyl groups are cis-oriented in the D-ring which is consistent with that of spirograterpene A. This structural data reaffirms the revised structure of spiroviolene, and further support the unified

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

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• NNG to glyoxylate, NH4+, and NO2−. NnlA homologs do not degrade 2-NAE Given the similarities in structure between NNG and 2-NAE, we sought to test if NnlA could also degrade 2-NAE. To test if NnlA could degrade 2-NAE, E. coli transformed with Vs, Mr, Pd, Pj, Ps, or Ms NnlA were incubated overnight at

• structure of oligomeric proteins [31]. The highest ranked model is shown in Figure 5. AlphaFold predicted a canonical α/β fold with high confidence, between residues Arg16 and Gly146 (Figure 5A). Structural clustering using Foldseek Cluster identified substantial similarities to other PAS domain proteins

• assignment of NnlA as a heme-binding PAS domain protein. As previously reported for a structural homology model of Vs NnlA, the heme position was estimated by overlaying the AlphaFold model with the structure of Pseudomonas aeruginosa Aer2 (Figure 5B). By this method, the His73 is located near the heme

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

• chlorosulfite 25 or the alkoxytriphenylphosphonium chloride 26, respectively. With heating, SO2 or triphenylphosphine oxide is extruded with a concerted migration of the neighbouring O8 leading to an oxocarbenium ion 27, which is then trapped with chloride giving the observed products. The crystal structure for

• levoglucosenone, cyrene and their derivatives, generating a unique set of bicyclic building blocks. Previous work on migration reactions in 6,8-dioxabicyclooctan-4-ols [18]. Mechanism for the rearrangement of 10, and Newman projection and the X-ray structure of 10d projected along the C4–C5 axis. Structures for

• 10a–c, preparation of 10d–f, and X-ray structure of 10e. Rearrangement reactions for 10a–f promoted by SOCl2. Reactions of allylic alcohols 15 and 18 with SOCl2. Appel reactions of dioxabicyclo[3.2.1]octan-4-ols 10a,e,f and 15. Some transformations for the skeletal rearrangement products 11a and 12a

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

• 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

• that the only difference between compounds 3 and 2 is the position of the hydroxy group [28]. Analyses of the NMR data of compound 4 concluded that it is an analogue of 2. In comparison with 2, compound 4 has a ketone carbonyl signal at δC 219.1 and we finally confirmed its structure by comparing it

• analysis (Figure 4b). In these experiments, CavA was found to hydroxylate drim-8-ene-11-ol (6) at the C-3 and C-7 positions to produce 8 and 9, respectively, while albicanol (5) was modified only at the C-3 position. Compound 7 is a known natural product, and its chemical structure was determined by

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• forms a dissociated hydrogen chloride aggregate in the form of complexes 103 or 105. An X-ray structure of complex 105 was reported and the reaction 104 → 105 is described in the report by Snyder, though not stoichiometric balanced. These complexes seem to play a pivotal role in the hydrochlorination

• and 3 in Table 7). The reaction with only oxidized ligand (dppeO2) also works indicating that structure 103 could also be the active hydrochlorination complex (compare entries 4 and 5 in Table 7). The applicability of the reaction is confined to highly reactive 1,1-disubstituted or trisubstituted

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

• unique structure of fullerenes, characterized by a fully conjugated closed-cage structure, containing a mixture of hexagonal and pentagonal rings, have been recognized for the unique electronic [2][3][4], optical [5][6], and mechanical properties [7][8]. Despite the notable achievements in fullerene

• photodynamic therapy photosensitizers (PDT PSs) [41] and magnetic resonance imaging contrast agents (MRI CAs) [42], which are the most relevant topics in fullerene biological studies. Aggregated fullerenes in the micelle structure may cause self-quenching of the excited state of PS fullerenes or may inhibit

• , and HMBC spectra (Figures S3–S9, Supporting Information File 1), all peaks corresponding to the pyrrolidine part, linker part, and oligo-Lys part were assigned as shown in the chemical structure. In the sp2 region of 5a (Figure 6a, top), 17 signals (1C × 3 + 2C × 13) were observed similarly to the

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

• compounds allowing for the preparation of porphyrins with different reactive groups such as hydroxy and amino derivatives capable for further functionalization and conjugation of these porphyrins to other substrates. In addition, conjugates containing maleimide or biotin entities in the structure of

• 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

• and the data are given in Table 1. The 11B NMR signals of compounds 5–7, 11, 12, 14, 18–20, 23, 24, and 26 are in the range from δ = −0.9 to −17.0 ppm confirming the closo-structure of the carborane polyhedra. Conclusion In this article a synthesis of A3B-type carboranylporphyrins as potential

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

• 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

• , achieving 52.5% higher production than controls without pH shock [67]. Conversely, the present authors were able to increase the production of antarlides, which have a 22-membered ring macrocyclic structure, by adding disodium hydrogen phosphate to the culture medium of Streptomyces sp. BB47 to prevent the

• . At a concentration of 182 μM, murecholamide exhibits biological activity in inhibiting the migration of HT29 cancer cells. The second HSM is noaoxazole (39), which was discovered in Streptomyces sp. HR41 [79]. This substance has a chemical structure with a methylated oxazole ring at the end of a

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

• uridylyltransferase (GalU) converts glucose-1-phosphate into UDP-glucose. Pu et al. introduced GjUGT74F8 from G. jasminoides into an E. coli strain overexpressing PGM and GalU and achieved the production of crocins [105]. Conclusion Crocins possess the characteristic polyene core structure of carotenoids and exhibit

• natural products, and their biosynthetic pathways have been extensively studied. The construction of efficient hosts for the heterologous production of crocins will be a practical solution for the industrial production of these important chemicals. Principal structure of crocin and crocetin derivatives

• (CCD), aldehyde dehydrogenase (ALDH), uridine diphosphate glucosyltransferase (UGT). Structure of crocin and crocetin derivatives. A, SG, G, GB, and GT represent the common substituents of the crocin skeleton shown in Figure 1. Heterologous production of crocetin (1) and crocins. Acknowledgments We

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

• structure of this intermediate as N-((S)-α-hydroxyisocaproyl)-γ-aminobutanoyl-S-ACP and also demonstrate that BaeJ-KS2 is not sensitive towards an inversion of the configuration in the α-hydroxyisocaproate moiety. This finding is in agreement with the phylogenetic analysis of KS domains from trans-AT PKSs

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

• method to produce analog libraries is critical for structure–activity relationship studies to enhance its specificity. Since the first total synthesis by Ohno and Izumiya in 1966 [31], tyrocidine A and its analogs have been synthesized by several groups employing viable strategies over the past half

• vancomycin-resistant S. aureus (VRSA). However, the recent discovery of daptomycin-resistant Enterococcus and S. aureus provided the impetus to develop novel derivatives that enable more comprehensive structure–activity relationship (SAR) and resistance mechanism studies. Multiple approaches have been

• understanding of the acidic lipopeptide structure–activity relationship (Scheme 4b). Surugamide B The cyclic octapeptides surugamides were isolated from several Streptomyces sp. and shown to be cathepsin B inhibitors [56][57][58]. According to a biosynthetic viewpoint, the corresponding modules consist of four

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

• GC–MS conditions. Based on these results, we proposed that AsCPS synthesizes CPP and that AsPS subsequently converted it to compound 1. Notably, Ar. sacchari MPU169 is known as a producer of myrocins (Figure 1A), which are known to exhibit antiangiogenic activity [33]. Based on the chemical structure

• peaks were not related to diterpenoids and were likely derived from the host strain. B) Chemical structure of (−)-sandaracopimaradiene (1)). GC–MS analysis of the enzymatic reactions. A) Extracted ion chromatograms (EICs) at m/z 272 of the extracts from the reaction mixture of AsPS and AsCPS; AsPS and

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

• can be found in bioactive molecules and have been tested in structure–activity relationship studies (Scheme 1A) [8][9][10]. Moreover, transformations have been developed to exploit the two functional groups simultaneously, for example through their intramolecular cyclization to form pyrroles in the

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

• structure – a linear hexapeptide with β-hydroxyaspartate and hydroxamate functional groups, serving in iron-binding coordination. Three new variochelins C–E (3–5) were characterized by varied fatty acyl groups at their N-termini; notably, 4 and 5 represent the first variochelins with N-terminal unsaturated

• , including soil-isolated plant pathogens. Results and Discussion Isolation and structure elucidation In this study, we explored the secondary metabolite potential of the soil-isolated Variovorax sp. H002, domesticated from the Medicinal Plant Garden of the Faculty of Pharmaceutical Sciences, Hokkaido

• 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

• to synthesise ligands featuring two chiral imidazolidin-4-one units linked to the pyridine ring at the 2- and 6- positions (Figure 1 – ligands I and II). These newly designed ligands represent tridentate entities. Such structure modification provides the ligands structurally conformable to well-known

• donor ability to pyridine. This change reduces the ring size within the ligand structure, potentially increasing the space available for coordinating reacting species, thereby possibly enhancing catalytic activity and enantioselectivity. We also aimed to assess the impact of alkyl groups at the 5

• -position of the imidazolidine ring on the enantioselectivity of the reaction. Hence, we developed a ligand incorporating an unsubstituted pyrrolidine ring instead of the imidazolidine unit (Figure 1 – ligand IV). This structure characterises a 'proline-type' derivative, enabling its use not only in a

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

• : aromatic nucleophilic substitution; azide–tetrazole equilibrium; 4-azido-2-sulfonylquinazolines; quinazolines; sulfonyl group dance; Introduction The quinazoline core is a privileged structure with a wide range of applications. Quinazoline derivatives exhibit a broad spectrum of biological activities

• out also with quinazoline derivatives 1b and 1c (Scheme 2), the structure features of which may slow-down the fast SNAr processes due to the substituents’ character. The desired products 4b and 4c were obtained in MeOH and isolated in 44 and 40% yields, respectively. Methanol is known to decrease

• hours without compromising selectivity. Although tetrabutylammonium azide (TBAA) is better soluble in DMSO than NaN3, practical challenges associated with its use led to the preference for NaN3. Confirmation of regioselectivity for the sulfonyl group dance products The regioselectivity and the structure

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• react with acceptors to produce reducing radical species, capable of reducing organic electron transport materials with a low electron affinity [4][5]. It is not only in modifying the molecular structure to improve the electron accepting ability that there is innovation in new organic electron transport

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

• member of the emerging ion-endohedral fullerene family, have attracted significant attention owing to the distinctive ionic properties originating from the ion pair structure consisting of a cationic endohedral fullerene core and an external counter anion. Despite being a relatively recent addition, Li

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

• 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

• HMBC δH 1.62 (H-23)/δC 84.6 (C-25), δH 2.18 (H-24)/δC 84.6 (C-25), and δH 2.18 (H-24)/δC 68.6 (C-26) revealed a terminal alkyne structure. Additionally, COSY correlations shown in Figure 2 revealed the side chain structure of 1 containing a terminal alkyne and a conjugated trans triene (C-15 to C-26

• ). We then focused on the macrolide structure of 1. Six HMBC, δH 0.94 (H-30)/δC 82.0 (C-3), δH 0.94 (H-30)/δC 38.3 (C-4), δH 0.94 (H-30)/δC 85.3 (C-5), δH 0.90 (H-31)/δC 82.0 (C-3), δH 0.90 (H-31)/δC 38.3 (C-4), and δH 0.90 (H-31)/δC 85.3 (C-5), along with COSY correlations shown in Figure 2, revealed a

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

• the complete structural determination of 3. To overcome this challenge in structural determination, we obtained a single crystal of 3 and performed X-ray diffraction analysis, which unambiguously established the structure of 3 as 5′-desmethylpreterretonin A (Figure 2C and Figure S1 in Supporting

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• existing ones. Keywords: GBB-3CR; imidazo[1,2-a]pyridine; microwave; phosphotungstic acid; Introduction Imidazo[1,2-a]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological