Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• rotate in this form [41], the structure can be termed rigid. Nonetheless, slight variations in the cavity height can be controlled by engineering the twist along the triptycene axis. For instance, comparing crystal structures of cage 2 and its monoacetylated analogue, 2Ac1 (Figure 9B), a decrease of 0.3

• ], which in many cases is the only way to understand pure substituent effects (e.g., on catalysis). To enable the validation of this process, experimentalists must collect data relevant to benchmarking computations: binding constants, kinetic barriers, crystal structures. In turn, this process will be

• permutations of amide conformations. Cages 1–4 have cavity heights rCC that change with carbonyl orientation (“macroflexibility”). Additionally, cavity heights can change within a conformation due to cage axial twisting (“microflexibility”). For cage 1, crystal structures have been measured for the more stable

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• diastereomeric ratios. The relative configurations of the various polycyclic compounds were clearly elucidated by determination of several single crystal structures. Keywords: allylic SN2 reaction; dimerization; isatin; MBH carbonate; 3-methyleneoxindole; Introduction Isatins (indoline-2,3-diones) possessing

• promoter is needed in the reaction, which is assumed to be due to the much higher reactivity of MBH maleimides of isatins compared to the above-mentioned MBH nitriles and formats of isatins. The single crystal structures of the compounds 5a and 5j were successfully determined (Figure 1 and Figure 2). From

• triene derivatives can be prepared under relative mild reaction conditions with good steric selectivity. The single crystal structures of compounds 7a and 8a were successfully determined by X-ray diffraction method (Figure 4 and Figure 5). From the crystal structures, it can be found that the compound 7a

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• present in the crystal structures. The results showed that C2-1 is more stable than Cs-1 by 3.85 kcal/mol at the B3LYP/6-311G(d,p) level of DFT. Additionally, C2-1 has a smaller gap (3.57 eV) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) compared

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• derivative were also recently prepared by a mechanochemical Scholl reaction [23][24][25]. Furthermore, the anion of TBF is stable enough to be easily handled and the crystal structures of a number of common ammonium salts of TBF anion, grown from water, have been reported [26]. Neutral highly acidic

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• examples are azide-porphyrin derivatives reported by Flanagan et al. [43]. Here, five crystal structures were obtained of meso-para-phenyl arm-extended porphyrins (26, 27, 28, 29, 33) and two crystal structures for meso-meta-phenyl derivatives 36 and 37. In addition, single crystal structures of 11 and 46

• were determined. All structures were investigated using the NSD method [8][9], which allows a quantification and visualization of distortion modes. It can be observed from the crystal structures that the porphyrins’ rings all exhibit the typical saddle-shaped conformation. Interestingly, substitution

• synthesis and a lower yield over two steps, this synthetic approach is disadvantageous. X-ray crystal structures were reported for almost half of these compounds. Crystal packing arrangements revealed this new library of arm-extended porphyrins as interesting candidates for the formation of supramolecular

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• , and dispersion forces (Edisp) of −12.5, −29.5, and −34.2 kcal/mol, respectively (Figure 6a–c and Figures S26–28 in Supporting Information File 1). Other sets of the ion pairs in the crystal structures showed smaller interaction energies. For example, the pair of 2+ and BF4− located at the side of TATA

• NMR spectra of new ion pairs, details for crystal structures, and theoretical calculations. Acknowledgements Theoretical calculations were partially performed at the Research Center for Computational Science, Okazaki, Japan (Projects: 22-IMS-C077, 23-IMS-C069, and 24-IMS-C067). The synchrotron

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• , chlorinated species 1h and 1i, and carboxylic acid-containing 1s, developed high quality crystals from standing solutions in dimethyl sulfoxide for 1h and 1i, and methanol for 1s. Their molecular crystal structures were determined and are shown in Figure 1b displaying the classic cone conformation for both

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• for the crystal structures can be found in Supporting Information File 1. As tosyl and benzoate groups are essential for the crystallinity of multivicinal organofluorines they influence the solid-state conformations [31][36][37][38]. Thus, information drawn from the crystallographic data of compound

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• halide abstraction is the crucial step towards the formation of a catalytically active gold species [18][19]. Furthermore, iodonium species 1BArF–4BArF have been shown to be halide abstracting agents in the Ritter-type solvolysis of α-methylbenzyl bromide and via the crystal structures of 1Cl, 2Cl, and

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• corresponding thiones. The yield of reaction products ranges from 42 to 80%. The crystal structures of catechols with 3-nitropyridine or 1,3,4-oxadiazole-2(3H)-thione moieties were established by single-crystal X-ray analysis. The possibility of forming intra- and intermolecular hydrogen bonds has been

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• formula of 9, the diaza-analog of compound 8-Hex that was reported previously [2]. a) Synthesis of the 1,2,3,4-naphthalene and -anthracene diimides. Conditions: i) CsF/Pd2(dba)3/MeCN; ii) NaOH/H2O/THF, then HCl; iii) R-NH2/AcOH. b) X-ray crystal structures of 7-Ph and 8-Ph. Summary and comparison of

• information file for compound 8-Ph. Acknowledgements We thank Victor G. Young, Jr. of the University of Minnesota X-Ray Crystallographic Laboratory for acquiring X-ray diffraction data and solving crystal structures. Funding The Bruker-AXS D8 Venture diffractometer was purchased through a grant from NSF/MRI

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• collected polyketide products were manually checked by literature searches. Absolute configurations determined entirely by chemical methods, such as crystal structures, NMR, chemical degradation and derivatization, were considered reliable. Alternatively, relative configurations determined by NMR methods

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• 3a and 3b resembled those of the hydrocarbon congeners, forming one-dimensional columns of stacked macrocycles (Figure 3b). The electronic effects of the nitrogen dopants in 3a were examined with X-ray charge density analyses [10][16]. For the crystal structures shown in Figure 3, we used a standard

• dopants. Photophysical properties of 3a and 3b. (a) UV–vis spectrum of 3a in CHCl3. (b) UV–vis spectrum of 3b in CHCl3. For reference, the spectra of [6]CMP and [8]CMP from the literature are also shown in gray [15]. Crystal structures of 3a and 3b. (a) Molecular structures. Biaryl dihedral angles (ω) are

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• -independent AlpJ-family oxygenases. Supporting Information Supporting Information File 44: Sequence comparison results and phylogenetic tree of AlpJ-family enzymes and anthrone oxygenases, crystal structures of AlpJ and ActVA-Orf6, SDS-PAGE of purified proteins, HPLC traces of prosthetic group identification

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• ) Å, which fall within the range of the corresponding values reported for the crystal structures of methano-derivatives of C60 [5][21][22][23][24][25][26][27][28][29][30][31][32][33]. It is noteworthy that these C–C bond lengths are longer than those of the reported siliranes [34][35][36][37][38][39

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• correlates with the trend reported for CDA inhibitors [47][51]. We also demonstrated that IIc- and IId-containing DNAs also inhibit full-length wild-type A3G with similar efficiency to that for the single catalytically active CTD [57][58]. Recently, analysis of crystal structures revealed that both dZ (IIc

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• -oriented heterocyclic systems. Some examples of biologically active isoxazolo[4,5-b]pyridines with antibacterial [8], anticancer [12] and cytotoxic [10][13] acitivities. Biologically active analogs of compounds 13. X-ray crystal structures of compounds 12c (top left; the second crystallographically unique

(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

• proposed as ortho-benzene isosteres (Figure 14) [48]. Comparison of selected exit vector parameters obtained from reported crystal structures [48][49] indicates high geometric agreement between the stellane and benzene cores. Substituent distance d, scaffold carbon distance r, and the substituent scaffold

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

• the X-ray crystal structures for 11a and 11b allowing for the unambiguous assignment of configuration. The chlorinated product 14 contaminating 11b exhibited a 1H NMR spectrum similar to the starting material 10b, except that the resonance for the H4 methine was shifted from δ 3.60 in 10b to δ 3.90

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

• conformational change after cyclization would afford the chair-chair conformation of 7 [19]. Supporting Information Supporting Information File 46: Experimental details, analytical data, tables of primer sequences, constructed plasmids, and A. oryzae transformants and figures showing the X-ray crystal

• structures, the biosynthetic pathway, and NMR data and spectra. Acknowledgements We thank Prof. Katsuya Gomi (Tohoku University), Prof. Katsuhiko Kitamoto (University of Tokyo), and Prof. Jun-ichi Maruyama (University of Tokyo) for providing the expression vectors and fungal strain. We are grateful to Dr

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• , dipyridoacenaphthene chloride dihydrate, its 2:1 complex with 4,6-dichlororesorcinol, and neutral dipyridoacenaphthene as a self-associate were obtained and structurally characterized for the first time. The dominant feature of all crystal structures is the intramolecular NHN hydrogen bonding in combination with π

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• in these cases (Supporting Information File 1, Figures S54 and S74). Crystal structures The solid-state structures of 2a and 2f were determined by single-crystal X-ray diffraction. The crystals were grown from concentrated solutions in toluene. A representation of the molecular structure of 2a is

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• compound 6e belonged to the P21/c space group. A comparison of the C1–S1 and C1–S2 distances recorded in the four crystal structures under scrutiny and those determined previously for 1,3-dimesitylimidazolium-2-dithiocarboxylate (IMes·CS2) and its more saturated analogue SIMes·CS2 showed that the negative

• trends observed on 13C NMR and IR spectroscopies for δ CS2 and ν̃ CS2 and support the hypothesis that the perpendicular arrangement between the CS2− and CCN+ units is retained in solution. Likewise, all the exocyclic C–C and C–N bond lengths in the crystal structures under examination were typical of

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

• similar to the one of the initial pose despite the fact that much a smaller part of the GAG is located at the first binding site. Hence a comparison of the binding position of the ligand with both crystal structures (3C9E and 4N8W) were carried out to reveal which binding site is preferred upon the

• reassociation of the ligand (Figure 6). It can be seen that the binding of the ligand to the protein at the end of the sliding in represents a combination of both the binding positions from the crystal structures and the RMSatd score obtained for the two different crystal structures are 4.1 Å and 8.3 Å for 3C9E

• sliding in process was done for the other complexes with their corresponding crystal structures and the one obtained after docking. The ligands’ RMSatd values (Tables S1 and S2 in Supporting Information File 1) show that in the majority of the complexes the final structure is more similar to the crystal