Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• by acid catalysis from renewable resources, such as sugars, lignocellulosic biomass and waste materials [18]. It can be used as a bifunctional precursor for the synthesis of pharmaceuticals, plasticizers, and different additives [19]. Furthermore, it is recognized as an excellent starting material

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• are also important precursors in the synthesis of various biologically active molecules and pharmaceuticals such as antidepressants, antiviral and antibacterial drugs [4]. Cyclopropanols and their derivatives are considered to be carbocyclic homologues of enols presenting similar chemical properties

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China 10.3762/bjoc.15.64 Abstract A detailed chemical investigation of the South China Sea soft corals Clavularia viridis and Lemnalia flava yielded four

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• flow [2][3][4]. One use of such multiple step reactions is, for instance, the on-demand production of pharmaceuticals using compact, reconfigurable continuous flow systems [5]. The combination of flow chemistry with 3D-printed reactors is also a growing terrain in the last years [6][7][8][9][10][11][12

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• the nature and reactivity of the chemical bond enabled chemists to use their knowledge to create new molecules and materials [3][4]. This development provided humankind with new chemical compounds, such as color dyes, pharmaceuticals, as well as polymers and plastics. Given its transforming nature, it

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• cycloaddition protocol. Keywords: [3 + 2]; alkyne; cycloaddition; cyclopropanes; dirhodium catalysis; N-arylaminocyclopropanes; Introduction N-Arylaminocyclopropanes 1 are important structural motifs for pharmaceuticals and are found especially in marketed fluoroquinolone antibiotics [1], such as

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• can be executed under simple reaction conditions with commercially available and inexpensive materials/reagents. In this regard biocatalytic reactions offer green and sustainable alternative routes to develop asymmetric syntheses of pharmaceuticals with varied stereochemical features [30][31][32][33

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• -dependent enzymes generally catalyze the breakdown and formation of C–C bonds adjacent to a carbonyl group [1][2]. The resultant 2-hydroxyketones are often chiral, so these enzymes are being increasingly studied for their use as biocatalysts in the preparation of pharmaceuticals and agrochemicals [3]. ThDP

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• Pharmaceuticals GmbH, Leberstr. 20, A-1110 Vienna, Austria 10.3762/bjoc.15.11 Abstract Tubugi-1 is a small cytotoxic peptide with picomolar cytotoxicity. To improve its cancer cell targeting, it was conjugated using a universal, modular disulfide derivative. This allowed conjugation to a neuropeptide-Y (NPY

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• pharmaceuticals, fragrances and agricultural products [1]. It is therefore important to develop methods for their preparation which can be suitable for a large scale production. In this context there is an increasing interest in reactions including ω-transaminases (TAs) which have been identified as a greener and

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• importance in bioactive compounds, pharmaceuticals, and as chemical intermediates for organic and inorganic synthesis [1][2]. As a consequence, the development of efficient and practical methods for C–Se bond formation is still a promising field of research in organic chemistry. Despite the several number of

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• units in bioactive natural products and pharmaceuticals. Some of these propellanes exhibit intresting properties like antibiotic, antifungal, anticancer, platelet-activating factor antagonistic and antibacterial activities. The propellane skeleton is present in many alkaloids such as aknadinine (1

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• ], quinolines are only present in approximately 2% of FDA approved prescription pharmaceuticals [2]. Recently, 2,3,4-trisubstituted arylquinolines such as BI 224436 1 [3][4] and 2 [5][6] have been shown to exhibit inhibitory activity against HIV-1 integrase that is essential for viral replication through

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• prefunctionalized arenes. Selected examples of sulfenylated heterocycles used in pharmaceuticals and material chemistry. Crystal structures of compounds 3a, 3d, 3e and 3i. (a) Changes in the fluorescence spectra (in this case intensity, λEx = 455 nm) of [Ir(dF(CF3)ppy)2(dtbpy)]PF6 upon the addition of 1,2,4

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• related to hinckdentine A received increasing attention as a source of new and useful pharmaceuticals. One well-established approach is based on the elaboration of a preformed indole ring, for example through cyclocondensation of 2-(o-aminophenyl)indoles with 2-cyanobenzothiazoles [14], aldehydes [9] and

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• methodologies have been developed to build new C–X (X = carbon or heteroatom) bonds [7][8][9][10] and they offer efficient routes to the synthesis of natural products, materials, agrochemicals, polymers, and pharmaceuticals [11][12][13][14][15]. Specifically, the first-row transition metal catalysts, which are

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• structural units present in many natural products, functional materials, and pharmaceuticals [1]. Consequently, a variety of strategies have emerged to access them, including Pd-catalyzed and Cu-catalyzed coupling reactions (Buchwald–Harting couplings and Ullmann reactions) [2][3][4]. However, these classic

• –C or C–heteroatom bonds has attracted more attention [8][9][10][11][12][13]. In particular, the formation of C–O bonds is widely used in the syntheses of pharmaceuticals and functional materials [14][15][16][17]. The direct hydroxylation [18][19] and acetoxylation [20][21][22] have been developed

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• the desired biologic effect in living organisms, while the other enantiomer could be inactive, cause whole other biological responses or might even have the opposite effect. Hence, for the total synthesis of natural products or pharmaceuticals it is crucial to generate chirality with high

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• pyridines, cf. 7e, is also very encouraging, as these find widespread use in pharmaceuticals as benzene isosteres, which are more polar and metabolically stable, but lack the – often problematic – basicity of regular pyridines. Compounds such as 7c are not commonly encountered, but definitely have the

• the modified substituted imidazo[1,2-a]pyridines contains scaffolds commonly found in pharmaceuticals, such as sulfones 9a and trifluoromethyl groups 9b. Hence, this publication provides an easy route to access scaffolds with diverse aromatic systems, allowing for the construction of interesting

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• coupling reaction is a powerful method for the synthesis of ubiquitous biaryls and has been extensively employed in the synthesis of natural products, pharmaceuticals, agrochemicals, and polymers. The reaction usually involves a palladium-catalysed coupling of aryl boronates with aryl halides in organic

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• , have been developed for detecting BPs in pharmaceuticals and biological materials [7][8]. Due to BPs′ high polarity, they are difficult to separate on reversed-phase columns. To make them more amenable to analysis, ion-pairing or complex-forming reagents were used to decrease the ionic character of the

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• intermediates in the synthesis of pharmaceuticals and various chemical entities such as allylic alcohols, benzoxathiepines, benzotiazepines, α-thioketones, α-substituted α,β-unsaturated enones, and β-hydroxysulfoxides [15]. Accordingly, a number of methodologies have been reported for their synthesis

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• (by electron-rich groups). This is leading to formyl-protected diarylmethanes with potential application in the synthesis of new pharmaceuticals and optoelectronic materials. This synthetic approach gives an access to a wide variety of functionalized ortho-1,3-dithianylaryl(aryl)methanes in 26–95

• protocol. Structures of biologically active diarylmethanes and commercially available pharmaceuticals based on the diarylmethyl moiety. Various synthetic approaches to diarylmethanols (literature review and this work). A general strategy for the synthesis of ortho-1,3-dithianylaryl(aryl)methanols 5 and 6

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• , and it plays a crucial role in the elaboration and composition of biological systems. Amide bonds are widely present not only in peptides and proteins but also in pharmaceuticals and many natural products. Among the methods for amide bond formation, the direct condensation of carboxylic acids and

• FPID/(4-MeOC6H4)3P will be described in the following part. Moreover, angiotensin I converting enzyme (ACE) inhibitory peptides, widely exist in plants and animals, can serve as potential antihypertensive pharmaceuticals [40][41][42]. The synthesis of two ACE inhibitory peptides proceeded smoothly in

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• -deficient and sterically encumbered aryl groups. Keywords: arylation; C–N coupling; diaryliodonium; hypercoordinate iodine; metal-free; Introduction Imides are important structural units in a range of approved pharmaceuticals and agrochemicals (Scheme 1a) [1]. Despite the general prevalence of imides, N