Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• Zeng-Wei Lai Rong-Fei Yang Ke-Yin Ye Hongbin Sun Shu-Li You State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China State Key Laboratory of Natural Medicines and Center of Drug Discovery, China

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• Road, Manchester, M13 9PL, UK Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, 37135, Verona, Italy Present address: Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France Present address: Drug Design and Discovery, Aptuit

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• reactions; Passerini reaction; sansalvamide A; Ugi reaction; Introduction Peptoids are an interesting class of non-natural compounds that have recently received much attention due to their wide range of biological activities, which makes them attractive candidates for drug discovery [1][2][3][4][5][6][7

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• . Keywords: asymmetric borylation; GAP chemistry; organophosphorous; N-phosphinylimine; Velcade; Introduction The synthesis of chiral α-aminoboronic acids and their derivatives has attracted much attention in the organic and medicinal chemistry communities because of their importance for drug discovery and

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• [21]. In view of its importance chromone has emerged as a pharmacophore in drug discovery programmes, leading to several drugs in the market (e.g. cromolyn and nedocromil) and thereby continuing to draw the attention of synthetic organic and medicinal chemists [22][23][24]. However, there are

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• Hiroki Moriwaki Daniel Resch Hengguang Li Iwao Ojima Ryosuke Takeda Jose Luis Acena Vadim A. Soloshonok Department of Chemistry, Institute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, United States Hamari Chemicals Ltd. 1-4-29

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• tetracyclic architecture is highly desirable for drug discovery. Traditional copper-catalyzed Ullmann-type C–N coupling has been a powerful method to form the carbon–nitrogen bond [15][16][17][18][19]. However, the utility of the reaction is limited by the necessary high temperatures, the requirement of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• carbopalladation sequence generating both, the B and the C-ring of the system in a single step. Further derivatisation included the cleavage of the silyl ether and two-fold benzylic oxidation to the quinone moiety. We believe that these natural product mimics might be of interest as useful candidates for drug

• discovery research. Several natural occurring anthracycline antibiotics. Total synthesis of daunomycinone 6 according to Hansen. Synthesis of simplified anthracycline derivatives. Retrosynthetic analysis of anthracycline aglycone mimics. Si: any silyl group. Synthetic route for the synthesis of various

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• -mediated conjugate trifluoromethylation of α,β-unsaturated ketones 1 with 3a.a Supporting Information Supporting Information File 548: Experimental section. Acknowledgements This study was financially supported in part by the Platform for Drug Discovery, Informatics, and Structural Life Science from the

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• nanomolar range [108][109]. CDKs are regulatory proteins, which play an important role in the cell cycle and are considered to be a potential target for anticancer treatment. This makes the aristolactams promising lead components for further drug discovery [108]. The similarity of the aromatic moiety of

• Enterococcus (VRE) [159]. Beyond that, the modest cytotoxic activity of 215 and 217 against human cancer cell lines makes them interesting lead components for drug discovery. The IC50 values of 215 for different leukemia cell lines range from 0.11–0.22 µM. For 217, an IC50 value of 0.32 µM against gastric

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• rapid construction, and the evaluation of their antibacterial activity is reported. Keywords: acylation; antibacterial; drug discovery; natural products; tetramate; Introduction The discovery of new antibiotic families with novel modes of action is a promising way to overcome resistant or virulent

• suitable for an evaluation for topical use [31][32]. Significantly, these results suggest that a drug discovery approach based upon deconstruction–reconstruction inspired by suitable natural products with demonstrable biological activity provides a route for the rapid assembly of compound libraries, which

• inhibitory activity) [7] and unnatural systems, such as 3-carboxamide tetramic acid 1c and 3-carboxamide piperidine-2,4-dione 1d (undecaprenyl pyrophosphate synthase (UPPS) inhibitory activity) [8] exhibit high levels of antibacterial activity (Figure 1). All these systems share a β-dicarbonyl core. A drug

Creating Complexity

• Donald Craig

Beilstein J. Org. Chem. 2013, 9, 1881–1882, doi:10.3762/bjoc.9.220

• synthesis chemists are engaged in the creation of novel polymeric materials with a wide range of applications, the conception and fabrication of new supramolecular architectures, and in the exploration of new regions of chemical space in the contexts of drug discovery and development. As synthesis nears its

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• ]. They have been used to synthesise many nitrogen-containing functional groups including α-amino carbonyls [2][3], peptidomimetics [4], natural products [5][6][7][8][9][10] and many heterocyclic small molecules [11][12][13][14][15][16][17][18][19][20][21][22][23][24] of importance to drug discovery

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• , it also inhibited the NA of four H1N1 swine influenza viruses with IC50 values between 0.59 and 1.64 μM. Therefore, katsumadain A represents an attractive lead structure for the anti-flu drug discovery [6]. We recently reported the biomimetic total synthesis of katsumadain C [7], a natural product

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• recent years, triazole-containing compounds have become potential targets for drug discovery [1][2]. A large number of 1,2,3-triazoles exhibit various biological effects [3], e.g., antiviral (1), antibacterial (2), antifungal (3) and anticancer (4) activities [4][5][6][7] (Figure 1). The 1,2,3-triazole

• in Figure 1) [8][9]. The 1,2,3-triazole moiety is a constituent part of many modified nucleosides or carbanucleosides with antiviral, anti-HIV or cytostatic activities [10][11][12]. However, the scope of triazole chemistry is not confined to drug discovery. There are an increasing number of

• cases; Table 1, entries 3 and 4). 1,4,5-Trisubstituted 1,2,3-triazoles are of notable importance in drug discovery. For example, several 1,2,3-triazole-4,5-dicarboxylates display significant antituberculotic activity in vitro [69]. Thus, a nonterminal alkyne, diethyl acetylenedicarboxylate, was

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• acid derivative; radical alkylation; Introduction γ-Lactams exist in many natural products and biologically active compounds and are one of the most important classes of compounds for drug discovery [1][2][3]. Substituted γ-lactams, in particular, have potential application in drug synthesis, but the

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• (GPCRs) were identified more than 30 years ago and have since grown to become the largest class of membrane-bound receptors and the single most common target type in drug discovery and therapy [1][2]. Excluding olfactory receptors there are 390 genes encoding GPCRs in the human genome, divided into three

• ][7][8]. The CaSR is involved in several calcium-regulation-related diseases including various types of hypo- and hyperparathyroidism, and its pronounced regulation of parathyroid hormone secretion makes it an interesting target for drug discovery [9]. Several potent CaSR modulators have been reported

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• a nitrogen atmosphere. Supporting Information Supporting Information File 46: Analytical data and copies of 1H and 13C NMR of 3a, 3c, 3h and 8d. Acknowledgements The authors thank the Open Source Drug Discovery (OSDD) program of CSIR, New Delhi for funding as well as the Department of

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• considerable impact in drug discovery. There is currently extensive research activity in synthetic chemistry for the preparation of various biologically active fluorinated products [1][2][3][4][5][6][7][8][9][10]. Of special interest among such materials are the fluorinated amino acids, which in most cases

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• pathways for NF-κB activation converge on the IκB kinases (IKKs), and more than nine signaling routes have been identified [6]. While IKKs therefore represent attractive targets for drug discovery programs, the selectivity envisioned for an acceptable therapeutic index has remained elusive as inhibitors of

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• redox states were operative. Keywords: agelastatin; aminohalogenation; iron(II); free radical; natural product synthesis; Introduction Marine organisms often produce bioactive substances that potentially serve as attractive resources for drug discovery. (−)-Agelastatin A (AA, 1), a cytotoxic alkaloid

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• pocket [6]. This distinctive shape has enabled for the design of highly selective ATP-competitive inhibitors of Hsp90. Through the efforts of multiple drug-discovery groups, many classes of inhibitors have been identified [3][5][7][8]. While much is known about the general types of structures that

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• increasing attention in drug discovery processes [17][18]. The ease of reaction in the intermolecular format has been successfully demonstrated by using both organic/inorganic azides as well as alkynes/diynes [19][20][21]. In contrast to its employment in an intermolecular format, intramolecular azide–alkyne

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• of pharmacophore-based combinatorial libraries [26] and identification of new peptidomimetic scaffolds of potential interest in drug discovery [27][28][29][30], we evaluated the THBC-DKP-based scaffold as a potential suitable motif for the creation of unusual reverse-turn nucleators. Reverse turns