Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• =CH]-Gly and Phe-ψ[(E)-CF=CH]-Gly for the peptide transporter PEPT1 was investigated (see Scheme 17) [51]. As the (Z)-monofluoroalkenes had a better bioactivity than the (E), the conclusion was that the transporter preferred the s-trans peptide bond. The Ki values obtained were also compared to the

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• membranes. The conjugation of adamantane with heterocyclic compounds also provides a method to modify the pharmacological profile and frequently leads to a new type of bioactivity. For example, N-adamantyl tetrazoles 1 and 2 (Figure 1A) demonstrate lower toxicity and, simultaneously, more potent activity

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

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• . This moiety is indeed presumed to play an important role in the bioactivity of agar-oligosaccharides [4][5][6]. As AnGal appears polymerized within the agarose backbone, a conceivable way to obtain it as a free monosaccharide would involve the cleavage of the glycosidic linkages of the polysaccharide

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• -oxochatancin (16). Determining the metabolome of P. longicirrum and its bioactivity, makes it evident that this seemingly vulnerable soft bodied animal is well protected from fish by its chemical arsenal. Keywords: chemical defense; chemoecology; natural compounds; Nudibranchia; Phyllodesmium longicirrum

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

• medicine, agriculture and in natural products synthesis [1][2][3]. In addition, structurally related indanes also showed biological activity and have been reviewed by Ahmed in 2016 [4]. Extensive studies on bioactivity of 1-indanone derivatives open up more and more new possibilities of their applications

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• available that allow the detection of several different natural product classes. Besides the traditional chemical screening and bioactivity-guided isolation, the exploitation of the inherent properties of natural products is also feasible. Consequently, simple functional groups of natural products like

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

• biosynthesis of reduced polyketides in bacteria by modular polyketide synthases (PKSs) proceeds with exquisite stereocontrol. As the stereochemistry is intimately linked to the strong bioactivity of these molecules, the origins of stereochemical control are of significant interest in attempts to create

• economic importance of these compounds, there is significant interest in trying to generate new versions of polyketides for evaluation as drug leads. The significant bioactivity of these compounds derives from their complex structures (particularly when compared to the typical products of chemical

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

• known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonyl)benzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• activate glorin-induced genes in the social amoeba Polysphondylium pallidum was evaluated by quantitative reverse transcription PCR, whereby both compounds showed bioactivity comparable to a glorin standard. This synthetic route will be useful in conducting detailed structure–activity relationship studies

• glorinamide 2: a compound with comparable bioactivity, that is hydrolytically – and thus metabolically – more stable than glorin (1) [14]. The molecules were shown to be bioactive, effectively mediating the induction of gene expression during early development, as determined by quantitative reverse

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• compounds having the spiropyrrolidinyloxindole core [14][15][16][17][18]. The 3,3’-spiropyrrolidinyloxindole unit is found in the molecular skeleton of a large family of natural alkaloids with remarkable bioactivity profiles and interesting structural properties [19][20]. Derivatives with the 2,3

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• stereostructure–bioactivity relationship in biologically active compounds [18][19], including selected prostanoids [20][21][22], we decided to synthesize all four rosaprostol stereoisomers 1a–d in enantiomerically pure form (Figure 2). The two rosaprostol stereoisomers 1c and 1d have an absolute configuration at

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

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• ); Introduction Deoxyglycosides are essential moieties of numerous bioactive natural products, and are prevalent subunits in antitumor and antibiotic agents [1][2][3]. Furthermore, 2-deoxy- and 2,6-dideoxyglycosides are crucial components for the pharmacology and bioactivity of many biologically active compounds

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

• was "not very well". Binding of the nanoparticle induced protein denaturation, with loss of bioactivity [42]. We hypothesized that this denaturation arose from interaction of the protein with the hydrophobic elements of the simple ligands we were using. This hypothesis led us to create what we call

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• -pyrrrolidinedione nucleus are indeed very few [4][5][6]. Even though this core can be considered an attractive target, synthetic studies directed to find new biologically active compounds are scarce as well [7][8][9]. The unique structure and bioactivity of leopolic acid prompted us to plan a synthesis which might

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• treatment of osteoporosis and related bone diseases [1][2][3]. In the last decades, at least three generations of dronic acid derivatives appeared [4]. (Aminomethylene)bisphosphonic acid derivatives are analogous species, that also have potential bioactivity in bone diseases, besides they display

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• species represents another partially characterised pathway that features an unusual cyclised RiPP [133]. Mature ComX is a secreted RiPP that functions as a signal in this QS system, and the cyclised residue is crucial for its bioactivity [134]. The precursor peptide ComX is modified by a isoprenyl

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• designed to tackle the sometimes cumbersome task of finding bioactive secondary metabolites of bacterial origin, i.e., mainly bioactivity- or chemistry-guided methods. An additional approach, complementary to the latter, arose in the late 1990s, when the first microbial genomes were sequenced, allowing

• an MIC value of 16 μg mL−1. Further bioactivity assays were impossible to carry out due to the minute amounts in which this metabolite is produced. Consequently, a synthetic approach has been utilized in order to overcome this problem, leading so far to the synthesis of the tricyclic core structure

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice

• useful for understanding the action mechanism of related drugs, as well as to drive the synthesis of new drug like compounds. Since the milestone work by Hansch and Fujita [1], a variety of MD´s have been developed to improve the correlation of chemical structures with bioactivity, ranging from

• ], but these are mostly complementary and are aimed at corroborating and/or rationalizing the results provided by the regression models, since the docking methodology itself provides intermolecular energies and docking scores that correlate with bioactivity. On the other hand, despite not encoding

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• see Table 2 and Table 3. Bioactivity tests Evaluation of antileishmanial activity L. donovani (strain LG13, MHOM/ET/0000/HUSSEN), L. infantum (MHOM/GR/2002/GH12) and L. amazonensis (MPRO/BR/72/M1845) promastigotes and the murine macrophage J774 cell line (American Type Culture Collection, Manassas, VA

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• complement the bioactivity of myxovirescins and, thereby, expand the prey spectrum. Alternatively, it is possible that the killing of M. luteus involves a different predation strategy (e.g., attack with hydrolytic enzymes). In any case, the coordinate production of antibiotics, such as myxovirescin A

• -positive bacteria. Bioactivity-guided fractionation then led to the identification of the gulmirecins as the active principles [87]. Chemically, the gulmirecins form a novel class of antibiotics together with the disciformycins [92], which were discovered in a different P. fallax strain upon a large-scale

• bioactivity data of the disciformycins suggests that the isovalerate motive is important for the antibacterial activity. Due to their potent effects against human pathogenic staphylococci as well as negligible toxicity, gulmirecins A and disciformycin B have become promising candidate compounds for the design

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• involved in inflammation reactions. The authors isolated 23, 24 and 27 from the feces of Trogopterus xanthipes (flying squirrel) by bioactivity-guided fractionation, and determined IC50 values for the pure compounds to be in the low mM range (1.33, 1.07 and 2.33 mM, respectively) [31]. Also estrogenic and

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs. Keywords: binding energy; bioactivity; cyclodextrins; hesperetin; naringenin; Introduction Flavonoids are secondary metabolites