Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• , αVβ6, and α5β1. These data indicate that in this case the cyclo[DKP-isoDGR]-α-amanitin conjugates are possibly internalized by a process mediated by integrins different from αVβ3 (e.g., αVβ5). Keywords: antitumor agents; cancer; drug delivery; integrins; peptidomimetics; Introduction α-Amanitin is a

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• ]. Utilizing these reagents, we have successfully synthesized a wide variety of bioactive organofluorine compounds [24][25][26][27][28][29][30] including fluorinated thalidomide (antitumor) [24], fluorinated donepezil (cholinesterase inhibitor) [25], and fluorinated camptothecin (anticancer) [26]. During our

• both concentrations, i.e., 1 μM and 5 μM (Figure 2), 3m has a lower IC50 value of 0.68 μM than that of 3k (2.45 μM), as evaluated by the MTT assay. The best potency and IC50 value (0.49 μM) was obtained for SF5 type 3p, which is quite impressive when compared to the well-known antitumor drug cytosine

• suggested that antitumor drug candidates could be designed by further structural modification of these compounds 3. Moreover, with 3p exhibiting the greatest potency against U937 cells with comparably lower toxicity against AGLCL cells, further biological studies using 3p including in vivo evaluation should

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• ], antitumor [1], antiasthmatic [12], and antiviral including anti-HIV [13][14]. Comprehensive synthetic studies of coumarins and their derivatives have been carried out [15][16]. Typically, coumarins are prepared by the acid-catalyzed condensation of 2-alkynoic acids and phenols or the condensation of β

• , it is known that 4-arylcoumarins have antitumor activity [42]. Therefore, the one-pot preparation of 4-arylcoumarins from 3-aryl-2-alkynoic acids via aryl esters and cyclization is attractive and important. Here, as part of our ongoing investigation of the synthetic use of diaryliodonium salts for

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• % de), the utility of this procedure was demonstrated by converting the minor (S,S)-diastereomer 6 into the orthogonally protected γ-hydroxylysine derivative 7 which is found in the potent antitumor agent glidobactin A [19]. Another chiral electrophile, such as aldehyde 8 prepared in five steps from

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• antibiotics [41]. Our aim in the present study was to synthesize functionalized pyrimidinone systems through rDA reactions. Many of these products are of high importance in drug design due to their diverse biological properties including antimicrobial, antiviral, antioxidant and antitumor activities. In

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazole (R = H, 16) was condensed with 38. It was attributed to cyclocondensation between 1-NH (5-aminopyrazole) and the carbonyl carbon of the enaminone. The compounds were found to have cytotoxicity against the normal fibroblast (BHK) cell line and antitumor activity against the colon cancer cell line

• effects is associated with pyrazolo[3,4-d]pyrimidines. They are known to exhibit antiviral [111][112], pesticidal [113], anti-inflammatory [114], antimicrobial [115][116][117], antileukemic [118], antitumor [114][119][120], pan-RAF inhibiting [121], tyrosine kinase RET inhibiting [122], CNS [123

• antitumor activities against various human cancer cell lines. The compound 198 with a pyrrolidine moiety was identified as most potent and promising member as it showed superior antitumor activities over other derivatives. Bakavoli et al. [115] reported the synthesis of pyrazolo[3,4-d]pyrimidine derivatives

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• groups decreased the yield of the reaction. A series of 2-alkylsubstituted benzothiophenes were prepared and the method was applied for the synthesis of antitumor agents. In the same year, the group of Singh published two similar, but metal-free procedures. In the first report a new photocatalyzed

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• the synthesis of 2’,3’-methano carbocyclic nucleosides via compound 24 (Scheme 5) [17]. Carbocyclic nucleosides are important synthetic targets because of their use as antiviral and antitumor agents [17]. Replacing the oxygen unit in the parent furanose ring with a methylene unit helps to stabilize

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• antimicrobial [35][36], antitumor [37][38][39], antibacterial [40], and anti-allergic agents [41]. In addition, compounds with this backbone are employed as kinase inhibitors and receptors [42][43][44] and as a tracer for PET imaging of β-amyloid plaques [45][46]. The conventional approach for the construction

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• -Aminobutyric acid is a major neurotransmitter used to treat epilepsy [52]. Analogs of this acid displaying antitumor activity, such as hapalosin, dolastatins, and caliculins were found in natural marine products [53][54][55]. Palacios et al. also described the Wittig reactions of 2-aminovinylphosphonium salts

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• ], antitumor agents [9], and are stimulators of guanylate cyclase [10], whereas imidazo[1,5-c]pyrimidines demonstrate anti-infectious effects in the treatment of brucellosis [11], etc. However, the chemistry, medicinal chemistry and pharmacology of imidazo[1,5-b]pyridazines, with the imidazole ring connected

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• the pharmaceutical field due to their significant potential to exhibit antitumor, antimicrobial, and antioxidant activities [1][2]. In addition to acting as a stimulant of the central nervous system [3], this class of substances plays an important role in drugs that are used to treat obesity, diabetes

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• , particularly antifungal [3][4][5][6] and antitumor [7][8][9]. The aglycone part of a saponin is termed sapogenin. Diosgenin, yamogenin, tigogenin, smilagenin and sarsapogenin are the most abundant sapogenins in nature [10]. They are linked via a glycosidic bond to a sugar unit, mainly D-glucose. Diosgenyl

• ]. Modifications of the amino group in this synthetic saponin led to analogs with promising antitumor, antifungal and antibacterial activities [24][25][26][27][28][29][30][31]. In this paper, for the first time, syntheses of diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside, its hydrochloride as well as N-acyl, 2

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• curcuma longa, and its analogues, the curcuminoids, have attracted much attention regarding their biological activities [1]. These include antioxidant [2] and radical scavenging [3], antitumor [4] and anti-inflammatory [5] activities, as well as HIV inhibition [6]. Despite showing activity against several

• ongoing research to increase the selectivity of antitumor active metal complexes [17][18][19][20][21][22], our focus was on the synthesis of curcuminoids that could serve as building blocks to attach sugars like D-fructose or D-glucose [23]. Due to the easy accessibility to azido sugars [24][25] we

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• [2][3], anti-atherosclerotic [4][5], antidiabetic [6] and antitumor activities [7], are presently receiving much attention. Studies focus not only on the elucidation of their biomolecular targets but also on their applications as medicinal supplements [8] and in food fortification [9]. Examples

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• compounds are frequently found in bioactive naturally occurring compounds, as well as in the synthetic pharmacopeia. Imidazo[1,2-a]pyridine is an important heterocyclic system present in many molecules featuring diverse biological activities, such as antiviral, antimicrobial, antitumor, anti-inflammatory

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• ; nucleoside; protecting groups; uridine; Introduction Nucleoside and nucleotide derivatives or analogues are biologically active compounds of major interest [1][2]. Their widespread applications span from therapeutic agents, such as antibacterial [3][4][5], antiviral [6] or antitumor [7][8] drugs, to

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• application of such medicaments are antitumor remedies and non-invasive diagnostic imaging agents for PET, SPECT and MRI methods [5]. The combination of porphyrin and heterocyclic moieties in one molecule is perspective for the design of new compounds with potential powerful pharmaceutical properties. Up to

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• [3][4][5], exhibit a broad spectrum of pharmacological activity, such as antibacterial, anti-HIV, antifungal, antibiotic, antitumor and immunosuppressive effects [6][7][8][9][10]. In addition, the one-pot cascade transformation has proven to be the key step in organic syntheses because of its broad

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• activities, for example with antitumor effect [1]. One of the main requirements of estrone anticancer derivatives is the lack of their hormonal activity. Several core-modified estrones have recently been produced and diversified in order to get selectively acting compounds [2][3][4]. One opportunity for that

• provokes an antitumor effect in hormone dependent cancers, hence 17β-HSD1 inhibitors could have good prospects as anti-estrogen therapeutics [17][18]. The recently synthesized halogenated 13α-estrones, in addition to their pharmacological importance, may serve as appropriate starting compounds for Pd

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• number of antiviral and antitumor drugs [3][4]. On the other hand, naturally occurring nucleosides, especially marine nucleosides, have also played an indispensable role in drug discovery, which make great contribution in the commercialization of cytosine arabinoside (Ara-C), adenine arabinoside (Ara-A

• , antiparasitic and antitumor properties. Kipukasins A–G were firstly isolated from solid-substrate fermentation cultures of Hawaiian Aspergillus Versicolor in 2007 (Figure 1) [11]. Later on, kipukasins H, I [12] and J [13] were also isolated from the fungus Aspergillus flavus, which was collected at the South

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

• ], and antitumor activities [11]. For example, the natural alkaloids berberine (IV) and narciclasine (V) possess antiplasmodial and antiviral activity, respectively [12][13]. Indotecan (VI) and its analog idimitecan (VII) were identified as topoisomerase I inhibitors, and were promoted into phase I

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• treating asthma and post-stroke patients [16]. 1,2,4-Triazolo[1,5-a]pyridines show antifungal [17], antitumor [18], and cytotoxic [19] activities. Both types of heterocyclic cores are readily available from N-aminopyridium salts and related pyridinium-N-imines via 1,3-cycloaddition reaction [20] or

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• biological activities have been reported for some of the other types of mesoionic heterocycles. For example, antitumor [27][28][29], antileishmanial [30] and trypanocidal [31] activities, as well as reduction of the phosphorylation efficiency of rat liver mitochondria [32], have been described for 1,3,4

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• ability, chromophoric properties, and antitumor activity as well [40]. We compared several CuI-based catalytic systems in the arylation of amine 3b with 4-iodotoluene as a model substrate. We found out that the CuI/L-proline combination with K2CO3 led to the target aniline 4 in excellent yield (Scheme 3