Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• in natural products and pharmacologically active compounds, thus economic and efficient methods to construct heterocycles are always highly desirable [1][2][3][4][5][6]. Benzothiophenes are important heterocycles that are one of the key motifs of anti-inflammatory, anti-estrogenic and anti-HIV drugs

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• amines. Moreover, this class of compounds is itself attracting significant attention from chemists and biochemists due to their bioactivity as herbicides, and anticancer, anti-inflammatory, analgesic or anticonvulsant agents [26][27][28][29][30][31]. Especially interesting is apremilast (brand name

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• , Australia 10.3762/bjoc.13.133 Abstract Background: Croton oil is the only commercial source of the diterpenoid phorbol (1a), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory

• crystallization step. A solution for these issues is provided, suggesting that the poor-reproducibility of croton oil-based anti-inflammatory assays are the result of poor quality and/or inconsistent composition of croton oil. Keywords: croton oil; diterpenoids; natural products; phorbol; transesterification

• this chemotype. Croton oil is used as a reference for in vivo anti-inflammatory assays, like the mouse-ear erythema assay, and it is tempting to suggest that the notoriously poor-reproducibility of the data from this assay [23] might be related also to differences in the composition of croton oil

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• hits for distinct biological targets [12][13][14][15][16][17][18][19][20], particularly antidiabetic 7 [20], anticancer 8 [18], anti-inflammatory 9 [16], and antibacterial 10 [19] (Figure 1). The described compounds 4–6 were prepared from o-phenylenediamine. Compounds 7–10 may be prepared from

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• , Alej Svobody 76, 323 00 Pilsen, Czech Republic 10.3762/bjoc.13.128 Abstract Like thapsigargin, which is undergoing clinical trials, trilobolide is a natural product with promising anticancer and anti-inflammatory properties. Similar to thapsigargin, it has limited aqueous solubility that strongly

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• , anti-inflammatory [28][43], antiviral [39][44], antidiabetic [45] effects and cancer cell growth-inhibitory features should be mentioned [29][46][47][48]. Ugi-4CR has been applied in the synthesis of natural products, as bicyclomycin, furanomycin, penicillin etc. [53]. The high combinatorial potential

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• the Mediterranean region, known in folk medicine to possess anti-inflammatory [30], antipyretic, and gastric antiulcerous effects [31][32]. Due to lack of competing flowers in Autumn, the plant attracts many pollinating insects including bees, wasps and some butterflies to feed on, an indication that

• young shoots exhibited strong fungitoxic effects [41]. Costic acid isolated from cypress pine (Callitris glaucophylla, Thompson et Johnson) exhibited termite-repellent activity [37]. In a study of its anti-inflammatory effects on the HaCaT keratinocyte cell line, costic acid significantly inhibited TNF

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• ], agrochemicals [5], dyes [6], fluorescent materials [7][8] and ligands of complexing agents [9][10][11]. Multiaryl-substituted pyrazoles are of special interest, with some drug molecules such as the nonsteroidal anti-inflammatory agent Lonazolac [12] or the well-known COX-2 inhibitor Celecoxib [13] as prominent

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• , such as analgesic [9], anti-inflammatory [10], antimicrobial [11], antidiabetic [12], and anticancer [13] to name a few. Some representatives of 1,2,4-oxadiazole-based drugs are shown in Figure 1. Libexin and oxolamine are used as antitussive (cough) agents [14], butalamine is a coronary vasodilator

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• ), artemisinin [2] (antimalarial agent) and α-pinene [3] (antibiotic, anti-inflammatory). Apart from bioactive compounds with applications as drugs/pharmaceuticals [4] or in the nutrition or agricultural sector, isoprenoids of minor structural complexity are used as bulk chemicals or fuel additives [5][6]. To

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• (Figure 1) [6]. Furthermore, the isoquinoline motif represents a privileged medicinal skeleton widely found in a number of natural alkaloids and pharmaceutically active compounds [7]. Some of them exhibit diversified biological properties, including anti-inflammatory [8], antibacterial [9], antiviral [10

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• ]. The thiophene is a core system of a large number of bioactive molecules such as antineoplastic agents [49], non-steroidal anti-inflammatory drugs [50] or compounds with antibacterial activities against several Gram-positive strains [51]. Thus, 3,5-disubstituted isoxazole derivatives were obtained by

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• derivatives) are also important structural motifs that are widely found in biologically active natural or synthetic products [44][45][46][47][48][49][50]. Compounds containing these rings have widespread biological applications as anticancer [51][52][53], anti-HIV [54][55], anti-inflammatory [56

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , have been performed. This review also covers the most important studies on the biological activity of 1-indanones and their derivatives which are potent antiviral, anti-inflammatory, analgesic, antimalarial, antibacterial and anticancer compounds. Moreover, they can be used in the treatment of

• allowed the synthesis of 60 in yields ranged from 31 to 56%. 1-Indanones exhibit a broad spectrum of biological activity including anti-inflammatory [41], analgesic [42], antimicrobial [43], antiviral [5], anticancer [44] and antimalarial [45] activity. A combination of two or more biologically active

• moieties may increase or decrease the biological activity. A series of isoxazole fused 1-indanones 64 with increased anti-inflammatory and antimicrobial activity has been synthesized by Giles et al. [46]. In this synthesis, diethyl phthalate (61) was reacted with ethyl acetate to obtain indane-1,3-dione

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• . Ibuprofen is the API of many nonsteroidal anti-inflammatory formulations widely used in the treatment of fever, rheumatoid arthritis and other inflammatory diseases [10]. From the chemical viewpoint, ibuprofen is the (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid. Its sodium salt is water-soluble and

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• are a class of natural compounds which are found ubiquitously in the plant kingdom. They are reported to possess a wide range of biological properties like anti-oxidant, antimicrobial, anti-inflammatory, anticarcinogenic and antiviral activities [1]. The phenolic acids are also reported to show in

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• [7][8][9][10]. Indole and indazolyl subunits are central to numerous alkaloids and are constituents of many classes of compounds that display a wide range of bioactivities such as antimycobacterial, anti-inflammatory, antihypertensive, anticancer, antidepressant, antidiabetic, antimalarial

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive

• platform is a three-step synthesis of the popular nonsteroidal anti-inflammatory drug ibuprofen ((R,S)-2-(4-(2-methylpropyl)phenyl)propanoic acid) starting from isobutylbenzene and propanoic acid (see Scheme 1). These starting materials undergo a Friedel–Crafts acylation using trifluoromethanesulfonic

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• triglyceride serum levels, this CD reduces cholesterol accumulation in atherosclerotic plaques by the modification of HDL-cholesterol levels. It is noteworthy that HDL and apolipoprotein A-I (ApoA-I) cause a dose-dependent reduction in the activation of CD11b (i.e., anti-inflammatory effect on monocytes

• , the researchers suspect that the CD boosts the activity of macrophages, enabling them to attack excess cholesterol without causing inflammation. Indeed, CD increases liver X receptor (LXR) involved in the antiatherosclerotic and anti-inflammatory effects as well as in the RCT improvement. Moreover, α

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• chemistry over the years [1]. Isoxazoles have been found in natural products [1], and they exhibit anticancer [2], antiviral [1], anti-inflammatory [3], antidiabetic [4], anti-Alzheimer [5] and many other types of biological activity [6]. Isoxazolines and isoxazoles have been applied as chemosensors, liquid

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• activities, including antibacterial, antiviral, antifungal, anti-allergic, anti-oxidant, and anti-inflammatory [348][349]. The treatment of endoperoxide 238 with Et3N gave 1,4-diketone 240 in quantitative yield instead of expected hydroxy ketone 239 (Scheme 73) [350][351][352]. The endoperoxide 238 is

• rearrangement is one of the steps in the synthesis of the natural compound angelone from Nauclea, a plant species widely acclaimed for its anti-inflammatory and antibacterial utilities in traditional Chinese herbal medical formulations [370]. A Kornblum–DeLaMare enantiomeric resolution was also used to obtain

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• broad range of biological activities such as antibacterial [11][12][13], antiviral [14][15], anti-inflammatory [16][17], antitumor [18][19][20], and anti-HIV [21]. It is found as the core structure in several drugs such as Zolpidem, Alpidem and Zolimidine (approved for treatments of insomnia, anxiety

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• , carbamate 138, hexahydrobenzothiophene 140 and benzothiophene 142 were converted to the corresponding bisphosphonates 139, 141 and 143, respectively (Scheme 30). The synthesized heterocyclic bisphosphonates showed anti-inflammatory properties. 3 Knoevenagel-induced domino reactions An efficient method into

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• :36.5 to 67.5:32.5 er). To demonstrate the utility of the transformation, the sulfur–carbon bond of 26a was reduced using Raney nickel to access (S)-naproxen (27), an anti-inflammatory drug (Scheme 6b). Inspired by the work of Pracejus, Tan and colleagues applied their C2-symmetric guanidine catalyst 30