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

• is the inversion of the configuration at C-13, which is accompanied by drastic conformational change for the overall molecule resulting from the cis junction of rings C and D [2]. The influence of inversion of the configuration at C-13 in 3,17-estradiols on their in vivo and in vitro estrogenic

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• features in a conceptual landscape are also employed. Sparse feature detection in vivo Detection of important features in the environment is critical for the long-term sustainability of life. For example, the roughly 100 million photoreceptors in a human retina cannot not directly transmit a picture to the

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• Stephan Scheeff Dirk Menche Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany 10.3762/bjoc.13.108 Abstract V-ATPase has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with

• to date with activities in the low nanomolar range [24][25], by binding to the functional transmembrane subunit c [26][27], and display highly potent growth-inhibitory activities against a range of cancer cell lines, both in vitro and in vivo [23][28][29][30][31][32][33][34]. In detail, archazolid

• inhibition of V-ATPase abrogates tumor metastasis via repression of endocytic activation [28], leads to impaired cathepsin B activation in vivo [30], modulates anoikis resistance and metastasis of cancer cells [31], overcomes trastuzumab resistance of breast cancers [32], blocks iron metabolism and thereby

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• performing system. Gold core: optical properties AuNPs, widely employed for biomedical applications, are characterized by inert nature, resisting to air oxidation and corrosion [30]. This chemical non-reactivity and inertness make AuNPs an outstanding candidate for the development of in vitro and in vivo

• devices [31][32]. Furthermore, in vitro and in vivo short term reduced toxicity of AuNPs has been widely documented [10][33][34][35][36][37][38]. AuNPs own a number of peculiar optical properties, strongly dependent on the size and the morphology of the metallic core. When AuNP dimension is comparable to

• of the drug from degradation or inactivation in vivo, the opportunity to control the drug release and reduce the systemic toxicity and the exciting chance to selectively target the damaged tissue. Despite the most common carriers are based on nano- and microparticles (i.e., albumin, poly(lactic-co

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

• . Costic acid exhibited potent in vivo acaricidal activity against the parasite. Initial experiments showed that the compound is not toxic for human umbilical vein endothelial cells (HUVEC) at concentrations of up to 230 micromolar (μM), indicating that costic acid could be used as a safe, low-cost and

• ]. However, there are no preceding data on the action of costic acid against varroa. In this publication we report the isolation and structure identification of costic acid as a component of D. viscosa, as well as in vivo and field studies providing strong evidence of the acaricidal action of the acid

• of the column with methanol to remove the polar components. Three fractions were obtained with the following TLC (silica gel 60, F254S) Rf-values: 0.90–0.80 (group A), 0.80–0.60 (group B) and 0.10–0.01 (group C). Each was tested in the in vivo assay. Biological activity was detected in the Rf 0.80

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

• performed in vivo substrate promiscuity tests following a combinatorial approach [41][66]. The resulting products entailed pimarane- and abietane-type diterpenes as well as the trans-clerodane type diterpene kolavenol, a putative intermediate in the salvinorin A biosynthesis. Other bifunctional diterpene

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• their in vivo applications are restricted [12]. Therefore, the development of fluorescent nanoparticles that are able to replicate QD fluorescence properties without exhibiting long term toxicity profiles, has become very relevant. The term carbon dots (CDs) has been coined to describe a new class of

• wide range of in vivo applications, which has been the topic of several recent reviews [13][14][15]. Following the serendipitous discovery by Xu et al. during the separation and purification of single-walled carbon nanotubes (SWCNTs) [16], the development of synthetic methodologies to access these

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

• useless in vivo. However, considering the enormous potential of abicoviromycin, syntheses of its additional analogs are reasonable. 1.3 From alkyl chlorides Radiolabeled tracers can supply precious information about structures of biocatalytic reaction networks. The [14C]1-indanone 175 has been used in the

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• type behavior, and still others having no effect on the stereochemical outcome. Most importantly, introducing the same Caffrey motifs mutations into DEBS KRs 1 and 2 housed within DEBS 1-TE produced no discernable stereochemical switch in vivo [78]. These results clearly show that within the context of

• is most often valine, but also alanine or phenyalanine. The role of these residues in stereocontrol was evaluated in vivo by site-directed mutagenesis of a derivative of DEBS 1-TE in which the KR domain of module 2 was replaced with the ‘reductive loops’ (DH-KR-ER tridomains) sourced from the DEBS

• hydrophobic interactions with the Tyr while being sterically accommodated by the relatively small Ser (Figure 7b). Finally, stereospecificity for the (2S)-isomer appears to lie in steric clashes that would occur between a (2R)-methyl group and both the Ser and His of the YASH motif. Nonetheless, efforts in

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• hit, the synthetic protocol must then be quickly expanded to tens of grams for early in vivo toxicity studies and hundreds of grams for further toxicology studies and clinical trials [1]. These swiftly changing requirements appear throughout the clinical development of active pharmaceutical

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• to the initiation of two human clinical trials, a phase I/IIa trial in 2013 and a phase IIb/III trial in 2015, by the National Institutes of Health (NIH), USA. However, the administration of high doses of HP-β-CD is inevitable to obtain the effects in vivo because HP-β-CD cannot enter the cells owing

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• ) contrast agents and positron emission tomography (PET) probes for in vivo studies. Conclusion In this study, we described a novel preparation method for end-reactive PRXs using 3 as an axle polymer for the PRXs. The terminal 2-amino-3-phenylpropyl groups of 3 prevent the dethreading of α-CDs after end

• click reactions, including ligand molecules for active targeting, radioactive molecules for in vivo imaging, hydrophobic polymers for the surface immobilization of PRXs, and hydrophilic polymers for acquiring water solubility. Accordingly, the azide group-terminated end-reactive 4a and 4b are expected

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• generation GPAs in clinical use are all entirely derived from in vivo biosynthesis [1][2]. The biosynthesis of GPAs is based around the initial synthesis of the linear heptapeptide by a type-I non-ribosomal peptide synthetase (NRPS) [5][6] and its subsequent modification by cytochrome P450 monooxygenases [7

• ]. The installation of the crosslinks has received significant attention using both in vitro [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and in vivo [27][28][29][30][31][32] techniques, largely due to the synthetic challenge that these modifications represent. In vivo studies initially

• by OxyE, which acts between OxyB and OxyA in the cyclisation cascade [27]. In vivo experiments also hinted towards the activity of the Oxy enzymes against the substrate peptides whilst they remain bound to the NRPS [29], and in vitro experiments performed with OxyB from the vancomycin biosynthesis

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• example MI-63 and MI-219, [15][16][17][18] have demonstrated cellular activity consistent with inhibition of MDM2-p53 binding and have shown in vivo antitumor activity [15][19] (Figure 1). Isoindolinones, belonging to the alkaloids family, are found in many natural products such as vitedoamine A

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

• their hemolytic activities. Indeed, several in vitro studies reported erythrocyte lysis although the toxicological implication in vivo is negligible. The lysis mechanism is related to their capacity to draw phospholipids and cholesterol out of the biological membrane (see below). Based on this, the

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• B Enduracidin A (7) and B (8) were first isolated from Streptomyces fungicidicus B 5477 from a soil sample collected in Nishinomiya, Japan (Figure 2) [1]. Detailed reports of the isolation procedures, in vivo and in vitro antimicrobial activity, physical properties and structure elucidation have

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• , phenols and amino groups is a classical protection method in multistep syntheses as well as a transient chemical modification to improve the bioavailaibility and bioactivity of hydrophilic drugs and natural polyols [1][2][3][4][5][6][7][8][9]. Several in vitro and in vivo studies on peracetylated

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• preparation of luciferins 3 involves straightforward condensation of CBTs 1 with D-cysteine (2) (Scheme 1). For BLI applications, luciferins are often generated in vivo from CBTs [4][5][6][7], which are easier to modify and handle due to their higher stability, cell permeability, and reactivity than the full

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• (−)-(E)-β-caryophyllene synthase (6) from Saccharothrix espanaensis were identified. The identified main and side products were the same as detected in headspace extracts from E. coli during heterologous expression of the terpene cyclase genes [32][33], confirming that the in vitro and in vivo

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• have been investigated for their potential applications in catalysis, photovoltaic cells and biomedical science [5]. Special attention has been paid to fluorescence responses of metal–terpyridine compounds permitting access to new sensors for bioassays and in vivo imaging purposes [6]. The

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

• of luciferin yields the peroxy compound 1,2-dioxetane. This four-membered peroxide cycle is unstable and spontaneously decays to carbon dioxide and excited ketones, which release excess energy through light emission (bioluminescence) [62][63][64][65]. The in vivo oxidation of cholesterol by singlet

• model of the in vivo oxidation of cholesterol (219) by singlet oxygen produces cholesterol-5α-OOH 220, which is subjected to a Hock reaction to form the aldolization product 221 and keto aldehyde (atheronal A, 222) (Scheme 64) [67]. Keto aldehyde (atheronal A, 222) exhibits proatherogenic activity and

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• (including us) could generate emulsions with diameters small enough (<200 nm) for use as in vivo delivery vehicles [60]. Once again, supramolecular chemistry came to the rescue. Anslyn showed that guanidinium groups bound strongly to carboxylates [61]. This led to the surmise that this interaction could be

• the cells can’t do [93]. We have even been doing some immunology [94], including turning on the innate immune system [95] and figuring out what macrophages like to eat [96]. We have plenty to work on just taking our systems where they need to go, be it in vivo or in the clinic [97][98]. Broader

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• cyclic compound 72 (Scheme 11b) [56]. This result has been confirmed by in vivo experiments of Shen et al. [59]. NonS was annotated as an enoyl-CoA hydratase and shows a high degree of up to complete identity amino acid homology to mostly uncharacterised enzymes in several other clusters of Streptomyces

• confirmed by partial in vivo and in vitro reconstruction of tetronomycin (Tmn, 149), RK-682 (146) and agglomerin A (147) biosynthesis [141][142][143][144]. It is however not clear, in which order the two sub-steps occur. Tetronate processing. Spirotetronates like abyssomycin C (148), quartromycin D1 (151

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• the development of superparamagnetic iron oxide nanoparticles (SPIONPs) because of their biocompatibility which allows there in vivo use both for diagnosis in magnetic resonance imaging and in therapy [1][2]. Most often, it is necessary to modify the surface of SPIONPs to increase the metabolic

• stability. To overcome this main drawback, the NP surface could be derivatized by various functional groups. These ligands have to possess certain chemical and biological properties as the flexibility, the hydrophilicity and an absence of in vivo toxicity. In addition, the nanoparticulate systems so

• coupling reactions with a drug, protein or antibody. The use of PEG polymers with chains of different lengths has also given satisfying results. This modulation would allow improving the nanoparticles stealth in vivo. Further studies in this area and their applications will be reported in due course

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• –imidazole polyamides; sequence specificity: DNA; triplex-forming oligonucleotides; Introduction The recognition and detection of specific sequences in native genomic double-stranded DNA (dsDNA) is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1][2][3

• activation or Mukayama reagents [19][20][21], TFO-MGB conjugates have been synthesized [11][22][23][24]. However, this method is not universal because it requires solubility of all reagents in organic solvents, which is incompatible with in vivo and in situ applications. In addition, according to our