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

• phosphodiesters by 105–107 by electrophilic activation of ester and nucleophilic activation of water or peroxide at the metal ion [101][102]. The takeaway message is that polarization is most effective when it is bifunctional. In enzymes, there is never just a nucleophile – there is always a metal, “oxyanion hole

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• , presumably due to entropic penalties. Three of four computed resonance forms were all found to be of approximately equal energy. Only the E-enolate form 6 (-N1H-E) was slightly higher in energy by 0.06 kcal/mol likely due to electrostatic destabilization of the oxyanion with N2, however, this difference is

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

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• '-carboxylates 83 in 5–10% yield as byproducts. The major products 84 were generated via Michael addition and the nucleophilic addition–elimination of the carbanion of the generated enolate moiety, while the oxyanion of the enolate moiety attacked the phosphorus to form the byproducts 83 (Scheme 18) [40][41

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• rationalized by the greater steric repulsion in the conformer of the respective oxyanion leading to the anti diastereomer compared to that from which the major, syn diastereomer is formed (Scheme 5). Notably, a compound analogous to 5a was synthesized with thiophenol in 78% yield. However, it turned out to be

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• berberrubine and berberine derivatives were synthesized by the Cu2+-catalyzed Chan–Evans–Lam coupling of berberrubine with arylboronic acids and subsequent 9-O-methylation. The reaction is likely introduced by the Cu2+-induced demethylation of berberrubine and subsequent arylation of the resulting 10-oxyanion

• the Cu2+-catalyzed coupling reaction with the boronic acid (Scheme 2). The regioselectivity of the latter reaction step is most likely determined by a stronger nucleophilicity of the oxyanion in the 10-position of 6 that is caused by the particular electron distribution in the intermediate 6

• , specifically because of the decreased electron density at the 9-oxyanion by linear conjugation with the quaternary nitrogen atom [39]. Nevertheless, the reactivity of intermediate 6 is still relatively low, as indicated by the low yields of the Cu2+-catalyzed coupling reaction, thus resembling the parent

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• '-tetramethylquercetin (4, conformation 4A). Conformation 4A has a structure in which the phenyl group is rotated due to the OMe group at the 3 position (the biaryl dihedral angle is +28.2°), and upon ionization of the OH at 5 position to the oxyanion, the planarity was not significantly restored. This may increase the

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• , which binds to the acetyl group of ACh, consists of Phe295 and Phe297 residues [21]. The oxyanion hole that interacts with the ACh carbonyl oxygen consists of Gly121, Gly122, and Ala204 [22][23]. In addition to the active site another binding site, known as PAS, is located around the entrance of the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• acyloxyphosphonium ion. This in turn reacts with the anomeric oxyanion to furnish the anomerically modified sugar with retention of configuration via anomeric O-alkylation. This mechanistic proposal is in agreement with observations by Lubineau et al., who could correlate the acidity of the employed nucleophile with

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• of these oxygens take place after the bond fission. The hydroxide-ion-catalyzed cleavage that dominates at pH >7.5, proceeds by pre-equilibrium deprotonation of the 2´-OH and subsequent attack of the 2´-oxyanion on the phosphorus atom of a monoanionic phosphodiester linkage, giving a dianionic

• recent DFT calculations have led to the conclusion that replacement of the p-nitrophenoxide leaving group with a less electronegative nucleoside oxyanion converts the mechanism more associative, which results in more marked acceleration compared to the background reaction [27]. Dinucleoside phosphates

• , one order of magnitude faster than the cleavage of the zwitterion. This observation has led to the conclusion that the monoanion reacts through a minor tautomer having the 2´-OH deprotonated and the amino group protonated. The protonated amino group may facilitate the attack of the 2´-oxyanion by H

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• , the strongly red-shifted broad absorption and emission bands correspond to the conjugate base 2cB. The red-shifted absorption of 2cB is the result of the formation of the strongly electron-donating oxyanion functionality that leads to a pronounced donor–acceptor interplay with the quinolizinium core

• ]. Notably, the chromophore of the oxyanion-substituted quinolizinium derivative 2cB resembles the well-established solvatochromic pyridinium-N-phenolate betaine dyes that are employed as polarity probes [53]. Correspondingly, the derivative 2cB shows a similar positive solvatochromism, i.e., a blue shift of

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• enzymes CorB and MxnB. The two cavities, each harboring one chain are depicted in green and blue, respectively. The phosphopantetheine arm of the ACP reaches into the T-shaped catalytic cavity through a third hydrophobic channel. The oxyanion hole is highlighted by a pink circle. In that way the two

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• to its greater affinity for β-CD compared to α- or γ-CDs. According to the study, soman forms an (1:1) inclusion complex with β-CD at pH 7.40. After its complexation into the cavity, soman reacts with a nucleophilic oxyanion formed from a secondary hydroxy group of the CD torus. As a result of this

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• expected, both the chemical yield and enantioselectivity were improved, and the adduct 5 was obtained in 92% yield with 80% ee. In our preliminary DFT calculation, the HB-donor moiety would recognize an oxyanion generated from phenolic OH of substrates with tertiary amine moiety of the catalyst. It was

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• an excess amount of Grignard reagent, the carbonyl groups are attacked simultaneously by the Grignard reagent and resulted in the formation of diol 11. When an excess amount of substrate containing carbonyl group was reacted with a limited amount of Grignard reagent, the oxyanion formed by the

Alkoxide-induced ring opening of bicyclic 2-vinylcyclobutanones: A convenient synthesis of 2-vinyl-substituted 3-cycloalkene-1-carboxylic acid esters

• Xiufang Ji,
• Zhiming Li,
• Quanrui Wang and
• Andreas Goeke

Beilstein J. Org. Chem. 2012, 8, 650–657, doi:10.3762/bjoc.8.72

• [1,2]- and [1,3]-acyl migration of 2-vinylcyclobutanones, leading to cyclopentenones or cyclohexenones, respectively [15]. Danheiser and co-workers reported an oxyanion-accelerated [1,3]-rearrangement of in situ reduced 2-vinylcyclobutanones, by applying mixtures of LiBu3BH-MeLi and HMPT to give

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• analyze the key principles of oxyanion reactivities. In this work, extended studies on base-promoted glycosylation are presented by using benzyl protective groups in view of preparative applications. Emphases are placed on the influence of the acceptor anomeric configuration and donor reactivities

• . Keywords: glycosylation; oxyanion; reactivity; regioselectivity; Introduction For the assembly of oligosaccharides the complex and challenging control of regio- and stereochemistry has to be solved. Various contributions have facilitated enormously the access to complex oligosaccharide structures so far

• glycosylations were elaborated on partially methylated glucopyranosides as model systems. This systematic approach allowed determination of the preferred positions for glycosylation and the establishment of an oxyanion reactivity scale. In addition to studies with different base promoters and donors, the first

Anion–π interactions influence pK_a values

• Christopher J. Cadman and
• Anna K. Croft

Beilstein J. Org. Chem. 2011, 7, 320–328, doi:10.3762/bjoc.7.42

• with the anion, as indicated by the distribution of the HOMO, which is confined to the naphthol portion of each molecule, and is in fact principally located on the phenolic ring (illustrated for 8 in Figure 6). This may, however, bring the oxyanion closer to the more positively charged periphery of the

Structural studies on encapsulation of tetrahedral and octahedral anions by a protonated octaaminocryptand cage

• I. Ravikumar,
• P. S. Lakshminarayanan,
• E. Suresh and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2009, 5, No. 41, doi:10.3762/bjoc.5.41

• −, HSO4−, H2PO4−), and octahedral (SiF62−, PF6−) anions etc. have not been reported with this system, although planar (NO3−) encapsulation and binding of H2PO4− by [H6L1]6+ have been observed [14][15]. By contrast, L2, as host has been extensively used for oxyanion binding [16][17][18][19][20][21][22]. In

• encapsulated [H8L1]8+ moiety. The bridgehead nitrogen atoms distance in complex 2 is 2.092 Å smaller than that in complex 1 although in both cases recognition of oxyanion is monotopic in nature. This difference in complexes 1 and 2 could be due to the different degree of protonation. In fact our recent study