Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• the molecular scaffolds of natural products [5]. During the past two decades, large amounts of genome information from thousands of organisms have become available. This allows scientists today to gain direct access to the encoded catalysts through expression in easy-to-handle heterologous hosts, such

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• reaction, among pericyclic reactions, is a very important synthetic approach to obtain several molecular scaffolds, including naturally occurring molecules, drugs, polymers, and heterocycles with promising biological activity. Especially, Diels–Alder reactions involving quinones and dienes as starting

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• (NPs) and therefore automatically increases the dispersibility of the catalyst throughout the medium, resulting in a higher catalytic activity [23]. 1,4-DHPs are considered one of the most useful molecular scaffolds in medicinal chemistry. The scaffold is the main constituent of several crucial drugs

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• uncovered, too. The oxidation of (rac)-31 under basic conditions delivered the conjugated diene (rac)-34, possibly through a deselenation/E1cB elimination sequence similar to the one shown in Scheme 22. Conclusion In conclusion, novel fluorine-containing, functionalized small-molecular scaffolds have been

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics

• ; chemoinformatics; Cu-catalysis; cycloadditions; molecular scaffolds; multicomponent reactions; Introduction The screening of small molecule libraries is a well-established approach in early-stage drug discovery to identify hit candidates for the development of drug leads. The application of unconventional

• molecular scaffolds to develop chemical libraries can increase the chance of finding compounds able to address the so-called “undruggable” targets, such as protein–protein interactions [1]. In this context, molecules containing one or more rings are of primary interest, as they will suffer a reduced

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• conditions through covalent approaches. By using common synthetic methodologies chemists are able to proficiently synthesize a variety of both natural and unnatural molecular scaffolds [4][5][6]. The era of supramolecular chemistry began with the introduction of coordination theory by Alfred Werner in 1893

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• powerful and widely applied methodology for the synthesis of such derivatives, including alkenylated molecular scaffolds with multiple stereogenic centers [14][15][16] and references cited therein. Diversity-oriented synthesis (DOS), with the aim of the preparation of structurally diverse elements of small

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• conditions. Recently, light-driven reactions of 2-methylbenzophenone (2-MBP) were reported to proceed smoothly under a MFP setup, furnishing highly diversified molecular scaffolds with enhanced yields and selectivities [6]. The chemistry is based on the ability of 2-MBP derivatives A of generating, upon

• Michael addition pathway (see Figure 1b) [6]. Prompted by the interest of developing novel light-driven microfluidic methods for the construction of biologically relevant molecular scaffolds, we investigated the reaction between MBP 1 and 3-unsubstituted coumarin (2a) and chromone (3a, Figure 1c). It was

• setup for higher scale production of 4a (top) and different molecular scaffolds 6a–9a accessible after simple manipulation (Ar = o-OH-C6H4). Light-driven reaction between 2-methylbenzophenone (1a) and coumarin (2a); selected optimization results. Supporting Information Supporting Information File 446

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• dearomatized products to generate chiral complex molecular scaffolds in a short and efficient way is one of the attractive strategies used in chiral hypervalent iodine chemistry. Kita et al. for the first time developed a new chiral I(III) catalyst 7 having a rigid spirocyclic backbone. They applied it for the

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• of molecular scaffolds, from the mono-chlorinated linear chain of fallachromenoic acid [2], to the pentahalogenated halomon skeleton [3] and encompassing many intricate polycyclic and macrocyclic structures with complex vicinal oxygen/halogen patterns, such as bromophycolide B [4] and dichotellide B

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule’s polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• incorporating different diversity elements. These different building blocks were then combined together in the couple phase to give the substrates for the next phase. Finally, in the pair phase various functional-group-compatible reactions were used to generate distinct molecular scaffolds. The build-couple

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• molecular scaffolds and tested for their gelation abilities. In another approach, modifications are made to known gelator scaffolds in the search for new gelators. These approaches have been used widely with a fair degree of success giving rise to gelator molecules with diverse molecular structures [9][10

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• nitrogen-containing heterocyclic systems [11][12][13]. Multicomponent coupling reactions (MCRs) have been combined with IMDA approaches to efficiently increase molecular complexity [14] and prepare complex molecular scaffolds for the synthesis of natural products [15][16]. While the Ugi–Smiles condensation

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. Keywords: cyclohexane carbonylation; fluorine containing building blocks: organofluorine chemistry; Introduction Selectively fluorinated building blocks

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• , a myriad of transformations involving MBH adducts have been reported, leading to a wide variety of molecular scaffolds of high diversity and complexity [10][11][12]. A number of reports have dealt with the conversion of the hydroxy group of MBH adducts into useful functionalities, such as halides

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• unsaturated building blocks. The approach involved the iterative attachment of a propagating and a terminating building block to a fluorous-tagged initiating building block. Metathesis cascade chemistry was used to “reprogram” the molecular scaffolds. Remarkably, in one case, a cyclopropanation reaction

• half of all known organic compounds are based on only 0.25% of the known molecular scaffolds [9]! This uneven coverage of chemical space is also typical of small-molecule screening collections [7][10]. Consequently, the biological relevance of most known scaffolds has been poorly explored. The field of

• of metathesis substrates by iterative attachment of simple unsaturated building blocks to a fluorous-tagged linker 1 (e.g., → 2 or 3). Subsequently, metathesis cascade reactions were used to “reprogram” the molecular scaffolds, concomitantly releasing the products from the linker (e.g., → 4 or 5) [14

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• assembly of complex molecular scaffolds. The emphasis is placed on the use of nitrogen-centred radicals, on the degenerate addition–transfer of xanthates, especially on its potential for intermolecular carbon–carbon bond formation, and on the generation and capture of radicals through electron transfer

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• of molecular frameworks between compounds [4][5]. Therefore, one of the key challenges in DOS is the development of strategies that allow the efficient generation of a range of complex molecular scaffolds. A large number of approaches towards this goal have been reported, with some of the most

• illustrate the potential power of two-directional synthesis in DOS. The use of two-directional synthesis allowed us to access a range of bicyclic and tricyclic molecular scaffolds, rapidly and efficiently, by following a common reaction scheme. The nature of the two-directional synthesis lends itself to the

• the future to be able to apply a two-directional synthesis approach to the DOS of a wide range of molecular scaffolds and structural classes. Overview of the DOS strategy. Synthesis of linear cyclisation precursors 1–4. AlCl3 catalysed tandem Boc-removal/bicyclisation processes; the yields quoted

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• centres (α or β), the presence of additional substituents such as sulfate or acyl groups and the overall degree of branching. The molecular diversity of oligosaccharide offers a valuable tool for drug discovery in the areas of biologically important oligosaccharides, glycoconjugates and molecular

• scaffolds by investigating their structural and functional impact. Currently, oligosaccharides are known to have functions in a broad variety of cell–cell interactions related to invading bacteria, viruses and cancer cells [1][2][3][4] and to play central roles in post-translational modifications of

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• heteroaromatic systems and, in this context, we have used a range of perfluorinated heteroaromatic molecules as synthetically versatile building blocks for the creation of new molecular scaffolds for drug discovery [14][15][16][17]. In this paper, we describe the reactivity of 5-chloro-2,4,6-trifluoropyrimidine