Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• -protein receptors consisting of seven intermembrane domains [28]. The quaternary structure including the membrane set up the active site. Approximately 370 different G-type proteins are known, that are linked with the odour perception. Because molecules can bind to an array of olfactory receptors

• generating a complex odour impression, an exact determination which proteins are linked to which smells or molecules is a very ambitious task. Hence, studies towards understanding interactions led to a Nobel Award in 2002 [29][30][31]. Even today correct modelling and protein crystallisation are immense

Probing of local polarity in poly(methyl methacrylate) with the charge transfer transition in Nile red

• Aydan Yadigarli,
• Qimeng Song,
• Sergey I. Druzhinin and
• Holger Schönherr

Beilstein J. Org. Chem. 2019, 15, 2552–2562, doi:10.3762/bjoc.15.248

• fluorescence was used to detect a lipid droplet in monkey aortic smooth muscle cells [16], for visualizing different proteins, such as lactoglobulin, casein and albumin [17]. In fluorescence lifetime imaging microscopy τf as a viable contrast parameter was employed to image lipid droplets in living HeLa cells

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• superfamily of membrane proteins that regulate many physiological processes [12]. Despite the high relevance of GPCRs both functionally and as a drug target [12], the first synthetic GPCR photochromic small-molecule ligands appeared only five years ago [13][14][15]. Since then, photopharmacology has been

• or proteins) can be also targeted by allosteric photochromic ligands. In an initial communication [7], we recently reported a photochromic ligand class that is based on azologization of a biaryl ligand class [24] and that activates the chemokine CXCR3 receptor (CXCR3), a GPCR endogenously activated

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• ‐time photomodulation of sirtuins in vitro. Keywords: azo compounds; epigenetics; photoswitch; sirtuins; stilbenes; Introduction Sirtuins are protein deacylases that cleave off not only acetyl, but also other acyl groups from the ε-amino group of lysines in histones and many other substrate proteins

• , 692; HRESIMS: calcd for [C12H9N4OF + H]+ 224.0760, found 224.0753; comp. purity (220 nm): 100%; anal. calcd for C12H9N4OF: N, 22.94; C, 59.02; H, 3.71; found: N, 22.95; C, 59.46; H, 3.92. Cloning, expression and purification of recombinant proteins: Expression and purification of Sirt1133-747, Sirt256

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• and is a major threat to yield improvement and food security in Central Asia [13]. Recent genome sequencing of 35 Australian strains of B. sorokiniana identified a known proteinaceous necrotrophic effector, ToxA, which confers host-specific virulence proteins and is proposed to be acquired through

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• amines [7][8][9]. Recently the group of Crowley showed that CSAs also co-crystalize with proteins modulating surface interactions mainly through interactions with surface-exposed lysines and arginines [10][11][12][13][14]. RSAs, in analogy to CSAs contain hydrophobic cavities and sulfonic acid groups

• protein crystallizations. Due to the interest in interactions with proteins we have selected basic amino acids as chiral bidentate amines to interact with RSAs. We have also studied interactions of RSAs with chiral tetradentate ligands (tetraaminocavitands) in order to evaluate the influence of a chelate

• , especially for those proteins that have surface exposed basic amino acids [25]. The 1:1 complexes of RSA 1 with tetradentate aminocavitand (R or S)-2 are also effectively formed in polar solvents. The complexes have capsular shape that is retained in methanol as manifested by DOSY coefficients and chirality

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• aromatic amines with SO2F2 or the fluorosulfurylimidazolium salt have been achieved for assembly of N-sulfonyl fluorides [1][30], which have served as important active precursors for the development of noncovalent inhibitors (Scheme 1, (1)) [1][30][31]. Amides are the key connections in proteins, amides

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• chemistry. The occurrence of an amide and/or ester bond is widely realized in organic molecules, proteins, natural products, pharmaceuticals, polymers and agrochemicals [1][2][3][4][5]. The conventional synthesis of amides involves the reaction of carboxylic acids or their derivatives such as acyl halides

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• organoammonium ions [10], and biomolecules [11][12][13][14][15][16][17]. Furthermore, modified Lissoclinum cyclopeptides were used for the construction of novel tubular and cage structures [18][19], as prototypes for mimicking multiple loops of proteins [20] and for homochiral supramolecular polymerization [21

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• non-fluorescent in aqueous solution, but become highly fluorescent in non-polar solvents or when they are bound to proteins and membranes [42][43]. This enhancement is commonly understood in terms of the relocation of the guest into the more hydrophobic environment. The decreased rate constant of

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• molecules [27], including some amino acids [28] and proteins [29]. They are also biocompatible: compared to other types of macrocyclic molecules such as cyclodextrins and cucurbiturils (which are also water soluble), p-sulfonatocalix[n]arenes do not exhibit any toxicity, which makes them applicable in

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• ]pyridine-4-carboxamides being SMYD2 inhibitors (an oncogenic methyltransferase that represses the functional activity of the tumor suppressor proteins p53 and RB); the similar structures can be obtained using the methodology of sequential Doebner- and Ugi-type MCRs. In the present work we combined several

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• proteins from the 93 Streptomyces species described above were collected. After removing sequences shorter than 50 amino acids, a total of 171,033 sequences were used to construct orthologous gene families using OrthoFinder – v 2.2.6 [53] applying the default setting (BLASTp e-value cut-off = 1e−5; MCL

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• of polar functional groups and non-polar surfaces which is reminiscent of the amphiphilic binding pockets within many proteins. In water, the aromatic surfaces in the tetralactam cavity drive high affinity due the hydrophobic effect and the NH groups provide secondary interactions that induce binding

• between the equatorial sugar hydroxy groups and the receptor NH residues and also in the CH···π interactions with the hydrophobic anthrylene sidewalls. This combination of noncovalent interactions closely mimics the sugar-binding behavior exhibited by lectin proteins. The Davis group has explored more

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• /bjoc.15.102 Abstract Galectins are carbohydrate recognition proteins that bind carbohydrates containing galactose and are involved in cell signaling and cellular interactions, involving them in several diseases. We present the synthesis of (aryltriazolyl)methyl galactopyranoside galectin inhibitors

• -linked glycans on the cell surface. Surface proteins such as integrins [6][7], vascular endothelial growth factor receptor [8], and lysosome-associated membrane proteins [9] are known to be crosslinked by galectins, giving galectins a modulating role in cell adhesion, blood vessel growth and cellular

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• carboxylic acids, allowing direct coupling of haptens to the carrier protein. Hapten conjugation reaction with carrier proteins BSA and KLH Test reactions on submilligram scale (0.1 mg hapten:0.1 mg BSA, 1 mg/mL protein) were performed with activated HF-1 and BSA, resulting in a moderate number of haptens

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• which lead to high requirements for the selectivity of reactions and often to tedious purification procedures, but encountering a pure compound in nature is quite rare. This does not result in reduced requirements for enzyme selectivity. The very opposite is mostly true, because proteins working in a

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• example for an application in biochemistry, Figure 1 shows a compound with cyclooctyne and maleimide as functional units. It was used as a "turn-on" fluorescence probe for cross-linking proteins [13]. The highly reactive cyclooctyne residue undergoes 1,3-dipolar cycloadditions with organoazides (copper

• . Bifunctional DAT as a cross-linker for proteins. The compound is a turn-on-probe, i.e., the fluorescence quantum yield Φ = 2% increased upon reaction with the target to Φ = 41%. High-resolution XPS of SAM 3. High-resolution XPS of SAM 7. Preparation of DAT–ALA conjugate 3 with fluorinated benzyl residue

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• peptides to endure mechanical stress in nature has allured scientists to evaluate the mechanical stability of proteins by using single-molecule nanomechanical techniques (e.g., magnetic and optical tweezers or atomic force microscopy) [3][4]. Additionally, the resilience of the peptide bond to mechanical

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• , diazocines are stable over several thousand switching cycles under air [19][24][26][27]. Notwithstanding their excellent properties, to date only 3,3’- and 4,4’- functionalized diazocine 2 and 3 have been implemented in polymers [19] and proteins [28]. Unfortunately, similar to azobenzenes, aminosubstitution

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• of Ac4GlcNCyoc (Figure 6B,C). MGE with glucosamine and galactosamine derivatives is of interest to investigate O-GlcNAcylation of intracellular glycoproteins [32][33][34][35]. To include intracellular proteins in our analysis, we performed Western blot analysis of cell lysates. HEK 293T cells were

• cultivated with Ac4ManNCp, Ac4GlcNCp, Ac4GalNCp, or Ac4GlcNCyoc for 48 h. Subsequently, cells were harvested, lysed and the lysate was cleared by centrifugation resulting in an enrichment of soluble proteins. After labeling with Tz-Cy3 the proteins were separated by gel electrophoresis and blotted. Equal

• protein loading was verified by Ponceau S staining. As observed earlier [26], Ac4GlcNCyoc resulted in a significant staining of proteins (Figure 7). In contrast, Ac4GlcNCp as well as the mannosamine and galactosamine derivatives showed only weakly labeled protein bands. The observation that Ac4GlcNCyoc

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• cytotoxicity [3]. A photoreactive derivative of the cytotoxic jasplakinolides, geodiamolides [4][5], or seragamides (2–6, seragamides A–E) [6] could also enable the search for additional targets in the cell, including proteins involved in transport or even membrane components. For this purpose, the 2

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• artemisinins action and also indicate that the methyl group at the C-3 position of artemisinin is possibly involved in lipophilic interactions with putative proteins essential for survival of the Plasmodium parasite. Derivative 2 will be used to attach further substituents at position 14 of artemisinin to

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• million proteins were deposited into protein sequence databases, such as UniProtKB [29]. More than 40,000 enzymes were biochemically characterized and the corresponding data is available in specialized enzyme databases, such as BRENDA [30]. This wealth of biological information provides a good starting

• misannotated proteins, which is caused by automatized annotation algorithms that are often based on “simple” sequence similarities [43][44]. In selected enzyme (super)families the annotation error can be as high as 90% [45], which masks or even impedes the identification of novel functions within a given

• enzyme (super)family. An example are reducing enoyl-CoA carboxylases that were for most of the time annotated as ordinary enoyl-CoA reductases, with which they are phylogenetically related [46][47]. Another example are RubisCO-like proteins [48] that are enolases [49], isomerases [50] and

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• have already used azatryptophans to study proteins with intrinsic green and blue fluorescence [27][28]. The azaindole moiety allows a linker-less incorporation of a fluorescent label with minimal disturbance. Therefore, four fluorescent derivatives of nematophin were designed and their synthesis