Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• . However, what Hammett pointed out [79] several years ago is still relevant today. The section of the “Solvolysis Revisited” review [31] dealing with kinetic solvent isotope effects (pages 168–169) illustrates the extreme complexity of this topic and the uncertainty as to the extents to which the ksie

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• , a mixture of products is formed, among which 22 and 23 are the majority. It is important to note that the complexity of the reaction of β-NQS with primary aliphatic amines has already been reported in the literature. Fieser and Fieser [71] studied the reduction potentials of various naphthoquinones

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• preparation of highly valuable diarylmethyl sulfones are relatively scarce [24]. In addition, the important link between structural diversity and complexity with bioactivity represented by sulfones has led to the goal of developing strategies to as many these pivotal scaffolds as possible. Isocyanide is an

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• consisting of a mixture of mono- and bis-arylated products, accompanied by a range of unwanted side products. The complexity of the mixture resulted in the isolation of compound 3a in a rather poor yield of 15% (Table 1, entry 1). Furthermore, this initial experiment elucidated that four equivalents (two per

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• outcomes, illustrating the complexity in understanding and designing efficient drug-delivery systems in biological environments. It needs to be considered that TPP, despite its positive charge, still carries large phenyl groups that render the surface hydrophobic. While this can affect protein adsorption

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• targeting of the small receptor molecule and, thus, reducing the need for complexity compared to enzymes or co-factors. Conversely, a multitude of geometries may need to be considered for anions with linear, coplanar, trigonal or tetrahedral topologies (Figure 1b) [5][10]. However, following the advances in

• halide anions can also engage as the nucleophile, which has been exploited in ring opening and related reactions (Figure 3b). In general, the idea of enantioselective ring opening produces two fixed stereocenters during one synthetic operation, increasing the complexity of the product significantly. This

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• organizational interactions. This complexity makes the detailed prediction of the transition state organization for the current process very challenging. However, we propose that the general structure 19 shown in Figure 3 is a reasonable representation of one of the likely pathways (the major ambiguities being

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. Nevertheless, the complexity and diversity of polysaccharides makes synthetic processes extremely laborious and time consuming. Several aspects are crucial to plan a successful polysaccharide synthesis. Properly designed starting materials and/or catalysts are required to ensure regio- and stereocontrol during

• suggested that XGs are not essential for the creation of the cellulose network [96]. The complexity and diversity of XGs hinder isolation from natural sources and complicates their description. A significant effort was put towards the development of enzymes for selective introduction of the side chains [97

• introduce the fucose residues [110]. Even though the complexity of plant polysaccharides hinders their synthesis, these compounds are highly desirable to dissect the different interactions taking place in the plant cell-wall. Recognition of the branched oligomers by glycosynthases proved to be limited and

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• -catalyzed cross-coupling reactions of coumarin derivatives [24]. Coumarins are a promising scaffold for design and development of bioactive agents, however it possesses a flat system [25]. One of the attractive benefits of introducing chirality in a drug candidate is that it leads to increased complexity to

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• environmental niches remained elusive and has been limited by their biological complexity. It was thus surprising to find that the environmentally abundant, fungivorous amoeba P. aurantium does not only graze on yeast but can specifically target filamentous fungi such as A. fumigatus. The mechanism of action

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• barrier crossing of PNAs by intravenous administration of PNA conjugated to OX26 murine monoclonal antibody to the rat transferrin receptor [165]. The limitation of this strategy was complexity of the construct and lack of clear evidence for the cellular uptake. The first report of using the PNA–peptide

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• reactions an ideal platform for the synthesis of molecules with increased molecular complexity. Keywords: hydroalkylation; hydrogen atom transfer; quaternary carbon center; radical addition; unactivated olefins; Introduction Natural product structures remain some of the main sources of inspiration for the

• synthesis of new bioactive compounds [1][2]. A careful view of the carbon backbone of these natural molecules reveals their high molecular complexity [3][4][5], which can be described by the presence of multiple stereogenic centers in the same molecule, a substantial fraction of sp3 hybridized carbons (Fsp3

• molecular complexity of drugs in drug discovery programs, aiming at molecules with better selectivity for biological targets [6][15][16]. One ideal way to achieve more complex molecular architectures is by hydroalkylation of olefins, a reaction that forms new C(sp3)–C(sp3) and C(sp3)–H bonds at the expense

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• separable regioisomers and their structures were confirmed by HMBC, as previously demonstrated. Removal of the need to orthogonally protect C4 expectedly reduced the complexity of the synthetic route and nine steps for the synthesis of donors of type 11/12 was reduced to five steps for 18/19. Moreover, the

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• steps. As before, (S)-malic acid (3) was chosen as the starting material because its inherent chirality reduced the complexity of the synthetic process. Given the fact that the target molecule has C2 symmetry, it was prudent that a synthetic route starting from a common C5 subunit be chosen, with

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• simplicity and complexity represented by the different scent molecules is impressive (Figure 4). The advantages of a flow approach Flow chemistry as a branch of organic synthesis has been reviewed extensively through several informative and educational articles [14][15][16][17][18][19][20][21] and books [22

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -radical cascade reactions could efficiently construct various carbocycles and heterocycles with multifarious structures and complexity [59][60][61]. Centered on this context, we give a clear overview on a variety of novel cyclization reactions initiated by EDA complexes from the recent years. In 2016

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• , sialylation, galactosylation, and GlcNAc-ylation events among the different knockouts, and with that of the full network in Figure 4, reveals that the most pronounced effects on ganglioside complexity occur with enzyme activities 1, 3, and 7, which result in fewer than 10 reactions each. That any structures

• have not been considered here, from a de novo standpoint, owing to the combinatorial complexity that would arise from equal participation of the donors CMP-Neu5Ac, CMP-Neu5Gc, and CMP-KDN. Chemical structure of ganglioside GM1a (a β-ᴅ-galactosyl-(1→3)-N-acetyl-β-ᴅ-galactosaminyl-(1→4)-[α-N

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• ][16][17]. The vicinal difunctionalization of olefins to introduce two functional groups across a double bond has appeared as a powerful transformation to rapidly increase molecular complexity in synthetic chemistry with improved efficiency [18][19][20][21][22]. Various transition-metal-mediated

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• their biological properties, bioavailability, and ADME [7][8]. While tremendous methodologies have been developed for the synthesis of organofluorine compounds [9][10], many of the laboratory methods are not always suitable for industrial production in terms of their synthetic complexity, handling, and

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• of an in-depth understanding of their function and mode of action. Owing to the large size of biomacromolecules, the high complexity of the processes in which they participate and the natural environment in which they occur, an integrated analytical approach is often required to succeed in revealing

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• pH 7.0, the free enthalpy is somewhat more negative for pH 7.0 due to the additional strong entropic effect in the whole scenario. This is different to the previously detected ΔG-encoded particle size in the electrostatic self-assembly [37], and demonstrates the higher complexity of the system under

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• , we have performed a number of different functionalizations of such cyclic systems with various complexity, and with a particular focus on the modification of sugar-derived lactams. As summarized in Scheme 1, this includes simple nucleophile addition to in situ-generated imines [23], the consecutive