Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• . According to the mechanism, the heterocyclic ring closes by the attack of the bulky radical -CO-HN• over the α steroidal side to circumvent the 1,3-diaxial interaction with the methyl group at C-10. Spiro-1,3,4-oxadiazoline steroid Shamsuzzaman et al. achieved the synthesis of 5’-acetamido-3’-acetyl-(3R

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• ]. A crystal structure was additionally obtained for tetrazine 1c. Bond lengths and angles were similar to those of known five-membered NHIs [25], including a strong intramolecular interaction between the nitrogen of the tetrazine and the hypervalent iodine atom (I1–N1: 2.44(4) Å; the sum of VdW radii

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

• biocatalytic applications. The co-crystallisation of LahSB with bound SAH provides important details about the structure–function relationship, the substrate–enzyme interaction, and the cofactor binding site (Figure 5). This structural information, including the residues involved in binding, is essential for

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• systems [5]. This conformational preference is attributed to an electrostatic gauche effect, where an attractive NH2+∙∙∙Fδ− interaction reinforces the well-known hyperconjugative gauche effect. Additionally, NH∙∙∙F hydrogen bonding has been proposed to play a role in stabilizing conformers of certain 3

• Figure 5 and Table 2. This disparity in stability was largely attributed to the relative orientation of the nitrogen electron lone pair and the adjacent C–F bond, facilitating an anomeric interaction characterized by nN→σ*CF electron delocalization. Isomer 2 also demonstrated such an orientation, but the

• , less stabilizing σCC→σ*CF interactions were anticipated. Moreover, besides the anomeric interaction, the pseudoaxially oriented C–F bonds in 17 and 19 facilitated efficient electron donation from vicinal antiperiplanar C–H bonds through σCH→σ*CF interactions (Figure 6). The methylene group separating

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• bacterial infections occur by adhesion to host tissues through receptor–ligand interaction between bacterial carbohydrate-binding proteins (lectins) and oligosaccharides at the host cell surface. Pseudomonas aeruginosa (PA), a Gram-negative, opportunistic and ubiquitous environmental bacterium, is known as

• reversible light modulation of their activity since each isomer shows distinct structural and electronic properties [13]. Photoisomerization-induced conformational and polarity changes may allow to increase or decrease the interaction with the target protein or receptors, then modulate the drug potency on

• different sizes and substituents are tolerated on the aryl aglycon, we decided to replace the aryl aglycon by photoswitchable azobenzene in both O- and S-galactosides (Figure 1B) to investigate their binding affinity and the influence of the photoisomerization on the lectin interaction. The ammonium group

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

• the sequence of both KR subdomains [13]. This suggests a strong domain–domain interaction between KR and DH, as observed in the structure of KR-DH-ER tridomain (Figure 2c) [24], and indicates that KRs in β-modules and γ/δ-modules may not be generally interchangeable for domain swapping. However, the

• KRC, the N-terminal helix αB and the lid region αFG located at the C-terminal of KRC (Figure 2d). Indeed, this lid region exhibits a direct interaction with the DH and DH-KR linker (Figure 2c). However, such interaction was not observed between the N-terminal helix αB and DH in the crystal structure

• of DH-ER-KR tridomain (Figure 2c). This finding suggests that the helix αB may have an allosteric interaction with DH or potential large conformational changes between DH and KR during catalysis. Sequence logo analysis of KRC from β-modules Based on the clear stereoselectivity-dependent clades

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor. Keywords: aryl halide; diarylhalonium; halogen; halogen bond; non-covalent interaction; Introduction Halogen bonding has emerged as an important attractive

• interaction in a wide range of applications that include crystal engineering, drug discovery and light-emitting materials [1][2][3][4]. Although, halogen bonding was first “observed” over 200 years ago [5][6] and the structural characteristics were elucidated in the latter half of the nineteenth century [7

• halogen-bond interaction of diarylhalonium salts with pyridine decreased with increasing s-character used by the central halogen atom in the bond opposite the halogen bond; this is effectively the s-character in the σ*-orbital [21]. Conceptually, halogen-bond donors are commonly described by the

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• conventional metal hydrides, such as tin or silicon hydrides. The reaction mechanism is interesting since first, a Lewis acid–base adduct is generated by interaction of Et3N with a boron atom of bis(catecholato)diboron (B2cat2, 19). As a result, one of the catecholate ligands experiences an increase in

• -mediated deoxygenative trifluoromethylation technique worked with both benzylic and unactivated thiocarbonates. The proposed mechanism starts with the homolysis of (bpy)Cu(III)(CF3)3 by blue-light irradiation, which produces CF3 radicals and (bpy)Cu(II)(CF3)2. Subsequently, the interaction between the CF3

• subsequently undergoes addition to B2cat2 (19) to produce the boryl radical 41. Here, the choice of solvent is also important. The interaction between DMF and the boryl radical 41 assists B–B bond scission to furnish the target borylated products and an intermediate 43, which is oxidized by [Ir(IV

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• Constantine V. Milyutin Andrey N. Komogortsev Boris V. Lichitsky N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Pr., 47, Moscow, 119991, Russian Federation 10.3762/bjoc.20.117 Abstract For the first time, the interaction of aroyl containing pyrano[2,3-d

• can be used as starting materials in the studied condensation. We tested this hypothesis using the interaction of ketone 1b and phenylhydrazine hydrochloride (2a). It was shown that reflux of the starting compounds in ethanol for 1 h leads to the target hydrazone 3b in 64% yield (Scheme 3). It should

• , t-BuNHNH2). Unfortunately, in this case interaction of ketones 1 with aforementioned hydrazines led only to a complex mixture of unidentified products. At the same time the use of benzhydrazide or semicarbazide in the similar condensation resulted in recovery of starting compounds 1. Further, in

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• 1b and SWNTs in these samples. The difference in the intensity and Raman shift of the signals in the radial breathing mode (RBM) region would be another evidence for the strong intermolecular interaction between Cu-nanobrackets 1b and SWNTs. The interlocking of the SWNTs may restrict its radial

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• -substrate interaction. Phenotellurazine-catalyzed cross-dehydrogenative couplings. Screening of new Te(II)-catalyst candidates. ODCB: ortho-dichlorobenzene. Phenotellurazine-catalyzed cross-dehydrogenative indole dimerization. Supporting Information Supporting Information File 84: Experimental section and

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• for long chained 2-fluoro-1,3-bis(silyloxy)-1,3-butadienes. In conclusion, the interaction of activated carbonyl compounds with chromones offer a great variety of different reaction pathways leading to various types of products with potential applications in materials science and medicinal chemistry

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• electronic push–pull interaction of the thiophene and the quinoline moieties via the alkyne. Finally, we focussed on the synthesis of tris-alkynylated quinolines starting from 3,4,8-tribromo-2-(trifluoromethyl)quinoline (11). Starting material 11 was synthesized in very good yield from quinolone 3 by

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• structure, it self-organized through π–π interaction between the oxamide motif and the aryl π-framework. Further, the CH…O=C interaction facilitated the formation of ladder-like packing in the solid state (Figure S36, Supporting Information File 1). The molecular structure of oxamide 13 is shown in Figure 3

• methyl anthranilate structure from the ideal Lewis structure. The lone pair electron of nitrogen was donated to the non-Lewis orbital (i.e., LP*) of the adjacent carbon C(4) (see Figure 8), with a high interaction energy of 93.62 kcal⋅mol−1. Such an interaction was not found for aniline and o-anisidine

• . Instead, for o-anisidine and aniline, the lone pair electrons were delocalized into the antibonding NBO (i.e., BD*) with a smaller interaction energy of ≈26 kcal⋅mol−1. In other words, as shown in Scheme 8, the lone electron pair present at the nitrogen atom was delocalized into the π-conjugated system

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

• interaction is even more distinct when inspecting the electronic energies (Figure S1, Supporting Information File 1), where we observe a significant stabilizing effect of the hydroxyl–cation interaction for F-OH and H-OH. This is clearly discernible from the C+···OH distances (Figure 4, Table 1) and visible

• from the NCI plots. In general, stabilization of some 5-7 bicyclic carbocations (e.g., F-OH and H-OH) are via C+···OH interactions, which are facilitated by the carbocation and hydroxyl functionality being located in the relatively flexible 7-membered ring. This type of interaction is absent in case of

• . Additionally, we carried out NBO analysis for other hedycaryol cations, and due to large bond distances between C+···OH, no such charge transfer is observed, i.e., E(2) = 0. In these cases, the interaction is likely of a classical electrostatic nature. Next, to better understand the influence of carbocation

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

• . The regioselectivity in the addition reaction of 1 with C70 was explained earlier in terms of the interaction between the HOMO of 1 and the LUMO of C70 [16]. The reaction mechanism of ethylene with a silylene substituted with thiolate ligands has been studied using theoretical calculations, in which

• 3 may involve the interaction of 1 with the LUMO of 2a. The HOMO of 2a is observed mainly around the cis-1 and e′′ bonds among the 6,6-bonds, although the cis-1 bond would not be susceptible to the second silylene addition because of its steric hindrance. Alternatively, the interaction of the LUMO

• . Also, the HOMO of 2a is observed around the cis-1 and e′′ bonds, although the cis-1 bond would be sterically protected from the second silylene addition. Alternatively, the interaction of the LUMO of 1 with e′′ bonds of 2 should be considered. Electrochemical measurements (CV and DPV) were taken to

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• indicates that the cation-coordinative interaction with the catalyst plays a significant role. Moreover, the mechanistic investigation suggested that the observed selectivity is due to the more reactive potassium manganate hydride towards the hydrogenation of imines to amines than the sodium manganate

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• economy of the overall process. A pertinent example of this technique is represented by the Wohl–Ziegler halogenation protocol, which is based on the stable and easily handled N-bromosuccinimide (NBS), which is able to slowly deliver molecular bromine through its interaction with bromide ions [17][25

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• their profound implications on device performance [1]. Among these interactions, hydrogen bonding (H-bonding, HB) as a highly directional noncovalent interaction can influence the structural, electronic, and optoelectronic properties of bulk materials [2][3]. Hydrogen bonding plays a crucial role in

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• Fe2p peaks and the increase in shake-up peak intensity of the C1s in the XPS spectrum proved the emergence of charge-transfer host–guest interaction in FeCp2-ACFs-150, supported by the red-shift of the G-band in the Raman spectrum. The six-times enhancement in the spin concentration in FeCp2-ACFs-150

• compared with ACFs indicates the spin magnetism of the non-magnetic guest FeCp2+ molecule induced by a charge-transfer host–guest interaction in the nanographene host. The larger ESR linewidth than that expected from the dipolar interaction estimated by the localized spin concentration suggests the

• exchange interaction between the nanographene and FeCp2 spins. The narrowing of the ESR linewidth of FeCp2-ACFs-55 upon higher excitation microwave power suggests the inhomogeneity of the environment for FeCp2+ molecules in the nanographene host. The observed induction of spin magnetism by the interfacial

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

• the catalyst undergoes reduction, therefore, rather using only CO, a mixture of CO–air (12:48 bar) was used with the aim of oxidizing the Pd(0) species in order to restore the catalyst able to catalyze the process again. The reaction mechanism proceeds with an initial interaction between the Pd(II

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

• result, the overall absorption intensity in the short-wavelength region was drastically reduced. This leads to the assumption that this absorption band is highly influenced by the dimethylamino group on the 5-phenyl group, even though the phenyl ring is twisted out of the plane. Interaction between the

• two π-systems is rather unlikely due to the twisted position of the phenyl ring. It is therefore reasonable to assume that this behavior is more likely to be related to a possible interaction of the dimethylamino group with the rest of the system. However, the combination of two dimethylamino groups

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

• activity even in the presence of millimolar concentrations of 2-NAE (Table S4, Supporting Information File 1). This observation suggests that binding in the substrate pocket is dependent on an electrostatic interaction with the NNG α-carboxylate, most likely from a lysine, arginine, histidine side chain or

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

• properties and to modify the profile of biological activity due to optimum fluorine lipophylic properties, and enhanced interaction with lipid membranes [12][13][14]. Pentafluorophenyl-substituted porphyrin systems are especially useful for the connection of various functionalities capable for coupling with

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

• . xanthus, which enhances the iron-scavenging capacity of M. xanthus and places S. coelicolor A3(2) M145 under iron starvation conditions. This chemical interaction activates the actinorhodin (8) biosynthetic gene cluster in S. coelicolor A3(2) M145. Onaka’s group reported that co-cultivation of

• , a unique case of activation of secondary metabolite biosynthetic genes by co-culture of actinomycetes and animal cells has been reported, which we outline in detail below. If microorganisms and animal cells are used, one might first imagine the interaction between humans and intestinal bacteria

• that substances that affect Wnt signaling can be produced in response to the interaction between animal cells and microorganisms. In addition, dehydropropylpantothenamide (53) was also identified using the same co-culture combination [123]. The second group of compounds identified included uniformides