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

• relaxed substrate specificity for all maturases in the aer BGC: All hybrid precursors were extensively modified with dehydrations, C-methylation, N-methylations, and epimerisations comparable to the AerA precursor [112][113]. PbtM1 from the thiopeptide GE2270 BGC is another example of a side chain amide-N

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• partition coefficient logarithm (log P), H-bond acceptor/donor count (HAcc/HDon), fraction of sp3-hybrid carbon atoms (F(sp3)), and rotatable bond count (RotB) are shown in Figure 5. It is apparent that the GBB chemical space contains many drug-like (69,043,101 molecules, 25%) and “beyond-Ro5” compounds (75

• count; F(sp3) – fraction of sp3-hybrid carbon atoms; RotB – rotatable bond count); compounds complying with specific Lipinski/Veber rules (MW ≤ 500, log P ≤ 5, HDon ≤ 5, HAcc ≤ 10, RotB ≤ 10 [38][41]) as well as compounds with F(sp3) > 0.5 are highlighted in blue, the rest of the compounds are shown in

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• yields (up to 97%) and high enantioselectivities (up to 98.5% ee) under mild reaction conditions. In addition, this protocol was further expanded to synthesize highly enantioenriched hybrid molecules bearing biologically relevant heterocycles. Keywords: α,β-unsaturated ketones; iminium catalysis

• (Scheme 2) were obtained in good to excellent yields (71–97%) and enantioselectivities (83.5–98% ee). Molecules containing two or more biologically relevant heterocycle motifs are receiving attention in drug discovery research [31][32][33]. The enantioselective synthesis of such hybrid molecules is

• such compounds might be endowed with potent biological activities. Under the disclosed optimized reaction conditions, the reaction between pyrazolin-5-one (2a) and indole-derived α,β-unsaturated ketone 1m was performed. The resulting hybrid molecule 3ma was isolated in 96% yield and 90% ee (Scheme 3

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• -deficient alkynes [59][60][61][62][63]. The in situ generated cyclic intermediate C has a resonance hybrid C’. Then, the further nucleophilic addition of the electron-rich enamino unit to 5-(alkylimino)cyclopenta-1,3-diene intermediate C gave intermediate D. At last, the coupling of the iminium cation with

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• experiments in solution, a one-pot cleavage from the resin combined with the CuAAC reaction to the triazole–pyrazole hybrid was conducted exemplarily and gave the target product 21gd in 30% yield. The solid-phase reaction route allows for roughly equally high overall yields compared to the solution synthesis

• ORTEP diagrams of triazole products 21sd and 21vg with the thermal ellipsoids shown at 50% probability. NaAsc = sodium ascorbate. One-pot synthesis of triazole–pyrazole hybrid 21gd. aOne-pot setup yielded 21gd with unknown impurities; bwith an additional evaporation step after the triazene cleavage, a

• quantitative yield of the target product 21gd was achieved. Solid-phase synthesis of azidopyrazole 19g and triazole–pyrazole hybrid 21gd by immobilization of aminopyrazole 14b on benzylamine-substituted Merrifield resin 22, NH-functionalization and cleavage. Reaction conditions: a) BF3∙Et2O, isoamyl nitrite

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• [PhImC4H9]+, the unsubstituted 4,5-dimethyl-1-phenyl cation of TAAIL 37 and the cations of TAAILs 40 (4-CH3) and 49 (4-CF3). The structures of the cations were optimized with Gaussian 16 [56], using the hybrid functional Becke3LYP [57][58][59][60] with the split valence triple-ζ basis set 6-311++G(d,p) [61

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• differences between t-Bu-FIDO and t-Bu-FIDS, the density functional theory (DFT) method was employed using the B3LYP hybrid functional. The 6-31G* basis set was used for the geometry optimization and frequency calculation. The thiocarbonyl group in FIDS was found to have an out of plane bending vibration

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• into the scaffold. Benzyl azide (6), obtained using a previously reported procedure [27], was used in the CuAAC reaction. The α-acetamide carboxamide 1,2,3-triazole oxindole hybrid 7 was easily obtained in 61% yield using Cu(OAc)2 as catalyst, ascorbic acid, DMF as solvent, and microwave reaction

• , 72, 74 and 84% yield, respectively. An exception was noticed for N-heterocycle units (pyridine and 1H-pyrrole) substituted in the same position, since compounds 8g, 8l and 8i were obtained in 56, 51 and 36% yield, respectively. The 1,2,3-triazole hybrid isatin compound 8n was obtained in 56% yield

• obtained using an Ugi four-component reaction (Ugi4CR). (B) The synthetic strategy reported in this work. Library of α-acetamide carboxamide oxindole hybrids 5 accessed via the Ugi4CR. Microwave-assisted CuAAC reaction to access α-acetamide carboxamide 1,2,3-triazole oxindole hybrid 7. Library of α

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• and hedycaryol were prepared from their corresponding SMILES string using the RDKit library [30]. Electronic structure calculations on these carbocations were performed using the hybrid DFT functional M06-2X [31] and with the range-separated hybrid meta-GGA functional ωB97M-V [32] with the 6-31+G(d,p

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

• compound is made through a trans-AT polyketide synthase–non-ribosomal peptide synthase (PKS-NRPS) hybrid [9][10]. Instead of using the classical domain organisation KS-AT-ACP with AT domains integrated into the PKS, trans-AT PKSs utilize discrete ATs that are not an integral part of the PKS, but rather

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

• and multifunctional enzymatic assembly, nonribosomal peptide synthases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS systems, which are organized into sets of functional domains known as modules and function through a similar mechanism [9][10][11][12]. Each NRPS module is composed of three

• domains along with their associated peptidyl carrier proteins (PCPs): daptomycin and A54145 PCP-TE [55]. A series of thiophenol-activated precursors were tolerated by these enzymes to produce daptomycin derivatives, A54145 as well as hybrid molecules of the two compounds, which pushed forward the better

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

• a result, a total of 0.4 Gbp reads were obtained. The reads were subjected to hybrid de novo assembly using SPAdes (v0.4.8) [23]. The assemblies were subjected to BGC prediction using antiSMASH (6.0.1) [24]. Generation of ΔvarG mutant The 1 kb upstream and downstream regions flanking varG were

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

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• process (Scheme 1c). In this process, the hybrid α-ester alkylpalladium radical species from diazo ester adds to the double bond of 1,3-dienes or allenes, followed by the allylpalladium radical-polar crossover path. As with the classical Tsuji–Trost reaction, a subsequent nucleophilic attack of an amine

• of the hybrid α-ester alkylpalladium radical generated from the diazo ester (Table 1, entry 10) [53]. Replacing Xantphos with rac-BINAP or DPEphos gave very low product formation, indicating that the type of ligand was crucial for this transformation (Table 1, entries 11 and 12). Changing the

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

• pathway; their non-terpenoid portions can be polyketides, indole, or shikimate-derived compounds [1][2][3]. Their hybrid nature significantly contributes to their structural diversity and wide range of biological activities. Although meroterpenoids are found ubiquitously in nature, as both primary and

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• different sequences of sulfated antennae. To facilitate deciphering of these terms, the abbreviations are also given with colors for the 6-arm, 3-arm, and the first extension term (Figure 9). High-mannose and hybrid-type N-glycans The above defined rules can also be applied to high-mannose, aka

• . Proglycan annotation of oligomannosidic and some hybrid-type N-glycans. Plant and insect N‐glycans. Since the xylose strongly indicates plant N‐glycans, a simplified annotation, possible with the macro‐term “La” for the Lewis A determinant, may be used (grey font). Provisional outline of how O-glycans with

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

• fungal-RiPP-like/T1PKS, 1 betalactone, 1 PKS type I/NRPS/indole hybrid, 1 fungal-RiPP-like/T1PKS hybrid, 1 NRP-metallophore/NRPS hybrid, NRPS-like/terpene/phosphonate hybrids, 3 terpenes, and 1 indole-related cluster (Table 5). BGC 7.3, identified as an indole-type gene cluster, includes genes for

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• Zhiyang Quan Takayoshi Awakawa RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan 10.3762/bjoc.20.50 Abstract Meroterpenoids are hybrid compounds that are partially derived from terpenoids. This group of natural products displays large structural diversity, and many

• enzyme that oxidizes C-5, thereby reacting with the electron between C-1 and C-2 [38]. In the future, such mutagenesis strategies will be applied to a wider range of oxidases to alter their reactivities and create an expanded range of products. Construction of artificial fungi–plant hybrid biosynthetic

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• of Fe3O4 nanoparticles (Scheme 15) [101][102]. This organic–inorganic hybrid material was synthesized by the immobilization of the dodecatungstovanadophosphoric acid (HPA) on TPI-Fe3O4 with N-[3-(triethoxysilyl)propyl]isonicotinamide (TPI), acting as the linker for the heterogeneous catalyst, while

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• [80] (Scheme 22A). The study showed that a photoexcited Pd0 species formed upon blue-light irradiation of Pd(Ph3)4, was able to promote the activation of NHPI esters via SET (Scheme 22B). The photoinduced electron transfer process between the Pd-photocatalyst and RAE 58 was proposed to form a hybrid

• alkyl PdI-radical species 115 which could then react with 1,4-butadiene (116) to form hybrid allyl PdI complex 117. Subsequently, it was suggested that the species 117 would lead to the formation of a π-allylpalladium intermediate 118 through radical recombination. Ultimately, nucleophilic attack by the

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole–DBDAP hybrid. Keywords: Buchwald–Hartwig

• than the one-pot method. The most important of which was the chloro-containing DBDAP 4e that can be used to synthesize the antipsychotic drug clozapine (see above), a triazole-hybrid with anticancer properties, and can easily be used as the key part in the synthesis of other drugs like dibenzepine and

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• have been published that record the dynamic behavior of a wide range of molecules and chemical reactions. One such process was the dimerization of C60 fullerene in a carbon nanotube peapod, i.e., hybrid structures consisting of fullerene molecules encapsulated in single-walled carbon nanotubes (SWCNT

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• simulations were set up. First, hybrid GAGs (Figure 1) were prepared and docked using RS-REMD to find the pose in the binding site with the lowest interaction energy. Then, the GAG was pulled away from the binding site until it was shifted 40 Å from the starting position. Afterwards, the GAG was pulled in

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• ability of electrons to transmit through the four-membered rings [32]. Phenylene-containing oligoacenes (POAs) The localization of π-electrons and the consequent decrease in band gaps observed in the [N]phenylene series have sparked interest in exploring acene–biphenylene hybrid structures. If this trend

• = 0.07), and compound 64 displayed almost no fluorescence emission (λmax,em = 497 nm, Φem = NA). Naphthazarin–biphenylene hybrid structures Taking the advantage of naphthazarin's bifunctional Diels–Alder reactivity, Swager and his team succeeded in the synthesis of POA-type structures incorporating

• selectively synthesize compound 87 through a hybrid approach involving the integration of both solution and surface chemistry techniques [53]. The key compound 96 to be used in the synthesis of POA 87 was synthesized in two steps. In the first step, 94 was obtained using a double Sonogashira cross-coupling

Thienothiophene-based organic light-emitting diode: synthesis, photophysical properties and application

• Recep Isci and
• Turan Ozturk

Beilstein J. Org. Chem. 2023, 19, 1849–1857, doi:10.3762/bjoc.19.137

• (OFETs) [26][27][28], capacitors [29][30], hybrid films [31], and photosensitizers [32][33][34]. Another important π-conjugated unit is triphenylamine (TPA), having an ionization potential of 6.80 eV, which is lower compared to many other organic cores, thus providing a strong electron-donating ability