Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• cytotoxic effects but showed no activity. A number of natural products seem to be produced by reaction of altenuene diastereomers (or of related compounds) with C3 building blocks, i.e., with lactic acid, pyruvic acid, or with acetone (Figure 17). Alternatain D (65) was isolated from Alternaria alternata

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• original Biginelli reaction shown in Scheme 1A was significantly extended by variation of the 1,3-dicarbonyl-containing building blocks. Many groups have elegantly demonstrated the synthetic versatility of numerous enolizable carbonyl components, including β-keto esters, cyclic/acyclic β-diketones, β-keto

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• has organic building blocks, both condensation [98] and post-synthetic modification [99] methods can be used to immobilise organocatalysts. Asymmetric organocatalysis is commonly achieved by pyrrolidone ligands, with great results in a variety of reactions, such as Michael [100] and aldol [101

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• determinants that govern specific molecular interactions. Keywords: computational tools; glycan–protein interactions; MD; molecular recognition; Review Introduction Carbohydrates also referred to as saccharides, sugars, or glycans, constitute one of the main building blocks of biomolecules, alongside lipids

• using the doglycans.py tool. (https://bitbucket.org/biophys-uh/doglycans/). 2. Glycam-Web carbohydrate builder [50]: Free online web-service that gives the possibility to model the 3D structures of molecules and complexes containing carbohydrates starting from monosaccharide building blocks, being also

• different monosaccharide building blocks is dictated by the values of different glycosidic torsion angles. MM calculations: Investigating the energetically favourable conformations of carbohydrate disaccharide units composing the molecule of interest represents a pivotal step for generating reliable 3D

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• . Titration of CMC with hydrochloric acid, followed by treatment with a mixture of hexamethylene diisocyanide and formalin led to the formation of compact particles with an average diameter of 40–80 nm (Figure 3A). These particles were the main building blocks for the construction of cage-like structures

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• pyrazoles. The review will primarily focus on two major categories: two-carbon and three-carbon building blocks as key intermediates, while other special cases will be summarized separately. Review (3 + 2)-Cyclocondensation – C3-building blocks as key intermediates The majority of the numerous pyrazole

• syntheses known in the literature are based on the condensation of 1,3-dielectrophiles and their synthesis equivalents as C3-building blocks, along with hydrazines as N2-building blocks [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Conceptually, the en route generation of these C3-building

• compounds 38 are also interesting building blocks in pyrazole synthesis. Through the reaction of 1,5-diaryl-1,3,5-pentanetriones 38 with hydrazines, Knorr synthesis of pyrazoles and Fischer indole synthesis can be combined in a pseudo-three-component fashion to give 5-(indol-3-yl)pyrazoles 39 (Scheme 11

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• : Allostreptomyces; β-alkylpyrrole; conformer; cytotoxic; DFT; 4-formylpyrrole-2-carboxylic acid; Introduction β-Alkylpyrroles are key structural motifs in biomolecules and functional organic materials [1]. For instance, β-alkylpyrroles are the main building blocks for the life-essential tetrapyrrole pigments

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• , the interest in CF3CH=CHCF3 (HFO-1336mzz) [6][7][8][9][10][11][12], CF3CH=CHCl (HCFO-1233zd) [13][14][15][16][17][18], CF3CH=CHF (HFO-1234ze) [12][19][20][21][22][23], and CF3CF=CH2 (HFO-1234yf) [12][20][21][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] as fluorinated building

• blocks has significantly increased in the last years. Recently, the E-isomer of 1,2-difluoroethylene ((E)-HFO-1132) has attracted attention as a new refrigerant due to the low boiling point, moderate flammability, and low toxicity [40][41][42]. Also, in patent literature 1,2-difluoroethylene has been

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• bifunctional building blocks (BBs) can quickly increase the diversity of these molecular libraries [6]. Hence, DEL practitioners constantly seek access to novel building blocks [7]. Amino acids (AAs) are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins

• , while also holding a crucial function in many biological processes [8]. Non-canonical amino acids (NCAs) are widely used in medicinal chemistry [9]. Not surprisingly, they also find broad use as bifunctional building blocks (BBs) for DELs. In an early example, an 800-million-members DEL utilized Fmoc

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• importance in medicinal chemistry, as it can be employed as a rational to expand bioactive chemical space to tackle lead optimization issues like lack of potency, efficacy, and selectivity or pharmacokinetic/dynamic issues. One of the most important building blocks (in the sense of participating in a vast

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

• achieved during the last five years, and classifies them into five categories: synthetic methods, building blocks, scaffolds, biological activities and physical properties. Keywords: Groebke–Blackburn–Bienaymé reaction; multicomponent reactions; heterocycles; imidazo[1,2-a]pyridines; isocyanides

• allow the reaction to take place under the mildest possible conditions. This search goes in parallel with the urge to use increasingly diverse and complex building blocks, up to and including DNA conjugates, which would be degraded under the classical conditions developed by Groebke, Blackburn and

• synthesis (DOS) where a single methodology should generate diverse scaffolds. This comprehensive review focuses on all these aspects, and has been divided into five chapters, describing, respectively: a) efforts to develop new and milder reaction conditions; b) the use of new building blocks; c) the

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• nature on the molecular properties of PASs. Our goal is to delineate specific structure–property relationships that may shed light on these prevalent, yet still mysterious, compounds and serve as design principles for future PASs. Data The molecules in COMPAS-2 contain 11 cyclic building blocks varying

• in size, composition, and aromatic character: benzene, pyridine, pyrazine, borinine, 1,4-diborinine, 1,4-dihydro-1,4-diborinine, borole, pyrrole, furan, thiophene, and cyclobutadiene (Figure 1A). These building blocks encompass 6-, 5-, and 4-membered rings with aromatic and antiaromatic character

• , and contain nitrogen, boron, oxygen, and sulfur atoms. Using these building blocks, we generated a chemical library of cata-condensed hetero-PASs (cc-hPASs) ranging in size from 3- to 10-ring systems, by combining the rings according to the annulation types shown in Figure 1B. The number, type, and

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• -substituted 4-pentenoic acids without additional substituents on the carbon–carbon double bond (Scheme 1c) [26][27]. Chiral α-substituted γ-butyrolactone products as important building blocks for pharmaceutical development were obtained in a highly enantioselective manner in our catalytic system using

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• 1, which contains a chlorine atom in the β-position, with convertible isocyanides 4a–d, para-substituted anilines 2a–e and monochloroacetic acid (3) as the smallest building blocks in a four-component reaction leads to the formation of the Ugi bisamides 5–8 (Table 1). Their structures offer several

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

• 1,2,3,4-naphthalene and -anthracene diimide motifs as productive building blocks in imide-based organic materials. a) Structures of previously reported naphthalene and anthracene diimide isomers. b) The novel 1,2,3,4-naphthalene and -anthracene diimides reported here. Superstructures for a) 7-Ph and b) 8

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

• , albeit less potent than the reference drug. However, many oxazolines showed improved selectivity, with greater separation of antiprogestational and antiglucocorticoid activity (Scheme 19) [38]. 1,2-Aminoalcohols have been extensively utilized as building blocks for synthesizing spiro-1,3-oxazolidin-2

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

• them group transfer reactions [21] and as building blocks [22][23][24]. The synthetic potential of NHIs has been previously studied in model transformations such as thioanisole oxygenation, oxidative lactonization, or diacetoxylation of alkenes [25][26][27][28]. In this work, we want to apply NHIs in a

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• Henning Maag Daniel J. Lemcke Johannes M. Wahl Department Chemie, Johannes Gutenberg-Universität, Duesbergweg 10–14, 55128 Mainz, Germany 10.3762/bjoc.20.148 Abstract α-Aminoacetophenones are identified as promising building blocks for the synthesis of highly substituted dioxolanes. The presented

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

• contrast to ribosomal peptide biosynthesis, many non-proteinogenic amino acids can be incorporated as building blocks. However, RiPP pathways are more flexible and they represent interesting biotechnological production routes. In this review, we will focus on post-translational methylation reactions. A

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• the characterization of a purified agarase belonging to the family GH-86 from Microbulbifer bacteria. Alginate lyases The polysaccharide alginate is produced by various seaweeds and bacteria [44]. Two building blocks, β-ᴅ-mannuronic acid (M) and α-ʟ-guluronic acid (G), are used to assemble alginate in

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• to overcome this [17]. For this reason, the fluorination of benzylic C(sp3)–H bonds has become particularly important in biologically relevant situations. Benzylic C(sp3)–H bonds are also present in a large portion of commercially available building blocks, highlighting the appeal for benzylic C(sp3

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

• ) [3][4]. The building blocks for PKS biosynthesis often include malonyl-CoA or methylmalonyl-CoA, which are loaded onto the ACP by the AT domain. Subsequently, the KS domain catalyzes the decarboxylative Claisen condensation between the ACP-tethered extender unit and the KS-tethered growing chain. The

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• additives in the petrochemical industry [3]. Besides, 2-benzylanilines also serve as valuable building blocks in synthetic chemistry [4]. The classical route to this kind of aniline derivatives usually starts from parent anilines, which undergo Friedel–Crafts reaction with acyl halides followed by carbonyl

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• ] and many more (Figure 1). On the other hand, with unusual geometry and high reactivity norbornadiene and benzonorbornadiene derivative bicyclic compounds attract great attention by researchers with their use as building blocks in different application areas such as polymers, solar energy storage