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

• . Tetrazole drugs, current assembly strategies, and novel building block strategy. Synthesis of tetrazole building blocks. Isolated yields. Substrate scope of Passerini products 3. Isolated yields. Substrate scope of Ugi products 4 and 5. Isolated yields. Synthesis of tetrazole building block 6. Isolated

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

• introduced during the elongation steps of modules 13–15, and not after complete assembly of the PKS backbone [19]. A phylogenetic analysis of KS domains from trans-AT PKSs revealed that these domains group together, if the structures of their processed substrates are similar, allowing for a prediction of the

• significant importance. Many KSs within trans-AT PKSs function as gatekeepers, facilitating the transfer of intermediates along the assembly line without participating in chain elongation. For instance, the final KS of the bacillaene PKS lacks condensation capability, but may serve to ensure proper double

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

• of monomers in the final product intimately correlates with the order of modules in the assembly line (Scheme 1a). Beyond several additional domains, including ketoreductase (KR), dehydratase (DH), enoyl reductase (ER), and methyltransferase (MT) domains and epimerase (E) domains, which are

• tylactone hexaketides, such as NAC thioester and thiophenol ester 49, which serves as the precursor for downstream enzymatic assembly. Thiophenol ester 49 was accepted by the two terminal of tylosin PKS modules (TylGIV and TylGV) in vitro, which are responsible for the last four carbon atoms assembly and

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

• Information File 1). The four fragments were combined by Gibson Assembly Reaction (New England Biolabs) to generate a disruption cassette: upstream-cmR-downstream. After the transformation of E. coli DH5α with the cassette-pRED, a HindIII site was inserted on the end of the cassette sequence to yield the

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

• -aminoimidazo[5,1-b]oxazol-6-ium motif, followed by salt metathesis using KPF6 leading to the clean hexafluorophosphate salt 9a in 67% yield after recrystallisation [4]. This two-step assembly of the 3-aminoimidazo[5,1-b]oxazol-6-ium motif was also applied to ynamide 1b affording the PMP-substituted salt 9b in

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

• , and molecular machines. In particular, the advent of artificial molecular machines [13][14], consisting of an assembly of molecular components that perform mechanical-like motions in response to specific stimuli, has inspired the development of stimuli-responsive molecular tweezers, which have

• by the addition of zinc(II) which opens the tweezers, releasing the guest and leading to the disappearance of the photosensitizing properties of the system. In an extension of this work, discrete tetranuclear Pt complexes with Pt–Pt interaction were obtained by self-assembly between 21 and

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

• of chemoselectivity can benefit from the multitude of mechanisms for their activation. Particularly, the use of RAEs in natural product total synthesis enables the assembly of strategic C–C bonds through radical coupling reactions that can draw from a wide range of reaction conditions (Scheme 37

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• conditions, including improvements in reaction time and yields. This approach enables the systematic assembly of lipid II and analogues that contain shorter polyprenyl chains, specifically farnesyl (C15), geranylgeranyl (C20), and solanesyl (C45). Such short chain analogues are valuable in several

• applications due to their improved solubility in aqueous systems. Assembly is achieved by integrating distinct carbohydrate, peptide, and polyprenyl phosphate building blocks. This modular synthetic method allows for the strategic substitution of constituent building blocks at different synthetic stages and

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• similar to AA [12][13], indicating self-assembly via the hydrophobic effect and π-stacking interactions (Figure 3a,b). The self-assembly in water was further supported by UV–visible analysis, displaying slight red-shifts of the anthracene absorption bands relative to the spectrum in methanol (Δλmax = +3

• the self-assembly of in average six PA-CH3 amphiphiles into a small aromatic micelle (Figure 3g). In a similar way, the generation of micelles (PA-OCH3)n, (PA-OH)n, and (PA-Im)n was confirmed via NMR, UV–visible, and DLS analyses upon dissolution of the corresponding amphiphiles in water (Figure 3c,d

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• 401 nt ODNs were synthesized and purified with CBP. The two were joined together using Gibson assembly to give the 800 nt green fluorescent protein (GFP) gene construct. The sequence of the construct was verified via Sanger sequencing. To demonstrate the potential use of the long ODN synthesis method

• . Keywords: automated synthesis; catching-by-polymerization; gene assembly; long oligonucleotide; synthetic biology; Introduction Long oligodeoxynucleotides (ODNs) are segments of DNAs extending beyond one hundred nucleotides (nt). Emerging research areas such as synthetic biology [1][2], protein

• the PCR assembly step. Because of this, misalignments may occur, and errors may be introduced. (2) PCR assembly of multiple short ODNs in one pot requires similar melting points of the multiple overlapping regions of the short ODNs. Therefore, the sequences of the short ODNs must be carefully chosen

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• . Additionally, the similar reaction with α-halogenated N-tosylhydrazones also afforded N-tosyl-substituted spiro[indoline-3,5'-[1,2]diazepine] in satisfactory yields. This protocol provides a convenient approach for the assembly of diverse highly functionalized spiro[indoline-3,5'-[1,2]diazepines] and also

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• . Our results proved that the CuAAC reaction catalyzed by copper(I) N-heterocyclic carbenes can be successfully used in the synthesis of [2]rotaxanes. This, combined with the fast and simple assembly of [CuCl(SIMes)] [45][46] could lead to the development of a Cu(I) NHC click chemistry in the field of

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• -pyrazolo[3,4-d]pyrimidin-5-amine followed by dimerization to give the final macrocycle. A convenient synthesis of the latter starting from 4-imino-2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine was developed. A plausible pathway for the macrocycle self-assembly is discussed. Some features of the

• structure and reactivity of the obtained macrocycle are outlined. Keywords: amidrazones; hexaazamacrocycles; pyrazolo[3,4-d]pyrimidines; ring contraction; self-assembly; Introduction The chemistry of polyazamacrocycles (PAMs) is currently one of the most rapidly developing areas of heterocyclic chemistry

• obtained instead [40]. Since this type of macrocycle self-assembly seems to be very promising, we decided to reproduce the Dolzhenko’s procedure, then study the macrocyclization in detail, and extend this approach to the synthesis of other polyunsaturated 1,2,4,8,9,11-hexaazamacrocycles. Herein, we report

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• calculate the electrostatic potential over an electronic density map as well. For hdz-NO2, results show the alternated slipped stack motif involves the assembly of portions with opposite electrostatic potentials. Computational calculations were performed in order to confirm some of the structural and

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• synthesising these systems, including cyclisation reactions, self-assembly, and their remarkable reactivity. The potential applications of porphyrin-crown ether hybrids are also highlighted. Moreover, the discussion identifies the challenges associated with synthesising and characterising hybrids, outlining

• the possible future directions. Keywords: crown ethers; porphyrinoids; self-assembly; sensors; supramolecular chemistry; Introduction Many areas of modern supramolecular chemistry, organic, inorganic, materials and coordination chemistry, are based upon macrocyclic compounds of specifically-designed

• ]. The CsF binding led to a supramolecular self-assembly process, inducing a sandwich host–guest complex formation in the solid state (Scheme 2). It was established that fluoride is preferred over any other halide anions. The binding of the ion pairs was observed in highly polar solvent media, but in the

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• procedure: Optimization of the R[4]A and sec-amine geometries was performed with the GFN2-xTB method using the ALPB solvent model with the “veryTight” accuracy using the xTB software package [29]. Complex assembly search (aISS) was performed using the “dock” function with “tight” optimization of the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• ]. Combination of CSA/TBAC formed an efficient activator system for this sulfenylation/intramolecular cyclization. In the same year, Zhao and co-workers reported the thiocarbocyclization of allenes 136 with N-(organothio)succinimides 1 as electrophilic aryl/alkylthio reagents for the assembly of indene-based

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• could act as an electron shuttle (potentially via a π-stacking assembly). The synthetic scope was extended to C(sp2)–P bond formations by trapping with phosphines or phosphites (Figure 12B), and in all these cases DIPEA was used as the electron donor (0.5–5 equiv). Arylphosphonium chlorides 20 that are

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• Universität Berlin, Arnimallee 22, 14195 Berlin, Germany 10.3762/bjoc.19.77 Abstract Automated glycan assembly (AGA) affords collections of well-defined glycans in a short amount of time. We systematically analyzed how parameters connected to the solid support affect the AGA outcome for three different

• purification steps. Keywords: automated glycan assembly; photocleavable linker; polysaccharides; solid-phase synthesis; Introduction Automated glycan assembly (AGA) is a solid-phase method that enables the rapid synthesis of complex oligo- and polysaccharides from protected monosaccharide building blocks

• mostly performed on cross-linked polystyrene resins equipped with photocleavable linkers [3], offering orthogonality to all the synthetic steps of the assembly, while selectively releasing the glycan at the end of the synthesis. In recent years, the implementation of new synthetic strategies [4][5][6][7

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• reactions [16][17][18][19][20][21][22][23][24][25]. Recently, much attention has been devoted to the development of new domino reactions containing reactive Huisgen 1,4-dipoles as key components for the assembly of many biologically important nitrogen-containing six-membered heterocyclic compounds [26][27

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• ] and the photoxenobactins [32]. A unifying theme in the biosynthesis of these natural products is the use of a thiotemplate-based assembly strategy [33]. The molecular building blocks that are needed for the biosynthesis are covalently bound via thioester bonds to multi-domain enzymes. The domains

• intermediate (1’). In massiliachelin biosynthesis this intermediate is further processed and elongated with another cysteine-derived thiazoline, which is eventually reduced [18]. A premature hydrolytic release of 1’ from the assembly line would give 1, which could be further modified to 2–5. Some corresponding

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/data_request/cif. Supramolecular assembly of TMeQ[6] and 1,2-bis(4-pyridyl)ethene (G). (a) UV–vis titration of G (3.0 × 10−5 mol·L−1, pH

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• conditions reported previously, we began our investigation using o-azidobenzaldehyde (1a), 2-oxopropanesulfonamide 2a, triphenylphosphine, and diethylamine as reagents for the quinoline-3-sulfonamide assembly (Table 1). The reaction mixture was stirred in MeCN at 95 °C for 6 h which led to a mediocre yield

• synthesis of 3-sulfonyl-substituted quinolines (sulfonamides and sulfones). The approach is based on a Knoevenagel condensation/aza-Wittig reaction cascade for the quinoline core assembly. Hence, o-azidobenzaldehyde, ketosulfonamide or ketosulfone were utilized as key building blocks. The method devised

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• exposure to alkaline environmental stimuli at pH 10.4, and the assembly and disassembly processes were reversible (Scheme 1). The introduction of the TBTQ-C6 host significantly improved the dispersion of the aggregates formed after the collapse of the spherical nanoparticles under alkaline conditions. In

• TPE labelling degree. Self-assembly behavior of CS-TPE in water. To investigate the self-assembly behavior of CS-TPE in water, the critical aggregation concentrations (CACs) of CS-TPE were determined by measuring their optical transmittance at different concentrations (Figure S2, Supporting

• to observe the morphology of CS-TPE aggregates. At pH 5.3, CS-TPE with Rf = 2, 10 and 20 mol % assembled into homogeneous spherical nanoparticles with average diameters of 131 nm, 166 nm and 236 nm, respectively (Figure 3a–c). This assembly behavior is supposed to be caused by the amphiphilic nature

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44