Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• LPS isolates from wild-type or laboratory-adapted Gram-negative bacteria, the clinical and cellular studies as well as structure–activity relationship investigations using native LPS are complicated and difficult to evaluate. The lipid A content of LPS generally comprises a complex mixture of

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

• structure and fascinating biology, mycolactones have inspired various total synthesis endeavors and structure–activity relationship studies. Although this review intends to cover all synthesis efforts in the field, special emphasis is given to the comparison of conceptually different approaches and to the

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

• Adam and Eve that automate drug development via cycles of quantitative structure–activity relationship (QSAR) learning and biological testing (Figure 3) [16][17][18]. Eve’s selection of compounds was more cost efficient than standard drug screening, and the robotic scientist has identified several new

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• iodosobenzoate group and the methylated oligosaccharide; (4) in case of soman, the degradation is enhanced by a cooperative effect observed between the imidazole and 2-iodosobenzoate when the latter is in close proximity to the macrocycle. A more extended structure–activity relationship study is envisaged to

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• -terminal cysteine (Figure 1B) [9][10]. Each pheromone causes the opposite type of cell to induce the reciprocal conjugation of the heterothallic cells, through the formation of a conjugation tube for mating. A structure–activity relationship study on tremerogen A-10 demonstrated that both the amino acid

• responses in B. subtilis and related bacilli [3]. Structure–activity relationship studies on the ComXRO-E-2 pheromone derived from Bacillus strain RO-E-2, which is a hexapeptide with a geranyl-modified tryptophan residue, revealed that the exact chemical structure of the geranyl group and the absolute

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

• allow for facile access to glorin derivatives required for structure–activity relationship studies. Eventually, these studies can lead to the construction of various chemical probes to identify the unknown glorin receptor. Syntheses of glorin and glorinamide (Scheme 1) started from commercially

• derivatizations. Glorin, as well as the hydrolytically more stable derivative glorinamide, were shown to display comparable glorin-induced gene expression in Polysphondylium pallidum. In future this synthesis will facilitate the construction of a library of glorin derivatives for a detailed structure–activity

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• biomimetic scheme in order to devise an efficient route to these natural products for structure–activity relationship studies. First the N-acylaminocarbinol reagent was prepared in the form of racemic 5-ethoxypyrrolidine-2-one ((±)-9) by the partial reduction of succinimide (8) with sodium borohydride at 0

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• level is required. For this reason, many research efforts were directed toward the investigation of the structure–activity relationship (SAR) between inositol phosphates and biomacromolecules. These studies require various regio- and stereoisomers of inositol phosphates [6][7] and have prompted 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

• activity against resistant strains of bacteria and favourable pharmacokinetics. Structure–activity relationship studies of teixobactin suggest that the rare non-proteinogenic amino acid enduracididine, is a key residue for potent antibacterial activity. This observation has driven the need for new

• inspired lead structure. Efficient access to enduracididine will enable ongoing structure–activity relationship studies of teixobactin and other lead compounds, for the development of much needed antibiotic drug candidates. Structures of the enduracididine family of amino acids (1–6). Enduracidin A (7) and

• B (8). Minosaminomycin (9) and related antibiotic kasugamycin (10). Enduracididine-containing compound 11 identified in a cytotoxic extract of Leptoclinides dubius [32]. Mannopeptimycins α–ε (12–16). Regions of the mannopeptimycin structure investigated in structure–activity relationship

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• and its analogues for structure–activity relationship (SAR) studies. Conclusion In summary, we have utilized the skeleton of D-glucose-derived homoallyl alcohol 3 as a chiral podium for efficient synthesis of the 8’R-glycosyl amino acid core of amipurimycin. With this protocol, we have synthesized the

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

• unusual 2,3-pyrrolidinedione system and developed a synthetic strategy towards new lead compounds with antimicrobial activity. Efforts to synthesize analogues to build a structure–activity relationship (SAR) profile and optimize the activity are underway. Structure of leopolic acid A. Synthesis of

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• containing oligosaccharides of different lengths and frame shifts [19]. Synthetic oligosaccharide antigens enable structure–activity relationship (SAR) studies of bacterial antigens [20] to better understand antibody binding and help to improve existing vaccine formulations. Two synthetic routes to prepare

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• mode of action of 4 and structure–activity relationship studies are ongoing and results will be reported in due course. BHL and OdDHL are two natural AHL-based signaling molecules used by P. aeruginosain quorum sensing. PQS is a natural quinolone signaling molecule also used by P. aeruginosa in quorum

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• also established that dithiocarbamic flavanones of type 4 display no such activity. Therefore, only flavonoids 5a–m were tested against Staphylococus aureus (Gram positive) and Escherichia coli (Gram negative) in an attempt to establish an antimicrobial structure–activity relationship. Minimum

• A previously reported class of tricyclic flavonoids has been extended with the synthesis of thirteen new derivatives. These compounds were obtained from the corresponding 3-dithiocarbamic flavanones under acidic conditions. A study of their structure–activity relationship was performed with regard

• –activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of

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

• provided insights into the structure–activity relationship of haliangicin were generated in this study [55]. The huge potential to synthesize novel metabolites in the genus Haliangium is further corroborated by a PCR screening-based study for PKS sequences in H. tepidum among other myxobacteria [56]. The

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• access to muraymycins and their analogues, some structure–activity relationship (SAR) studies and first insights into muraymycin biosynthesis. It therefore provides an overview on the current state of research, as well as an outlook on possible future developments in this field. Keywords: antibiotics

• ; natural products; nucleosides; peptides; structure–activity relationship; Introduction The treatment of infectious diseases caused by bacteria is a severe issue. With multiresistant bacterial strains rendering well-established therapeutic procedures ineffective, the exploration of novel antimicrobial

• reflect several effects such as target interaction, cellular uptake and potential resistance mechanisms of the microorganism. MIC values are therefore widely used, also in studies on muraymycin analogues (e.g., [22][76][77][78]) and have been the basis of many structure–activity relationship studies (see

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

• suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. Keywords: conformational analysis; isoflurane; QSAR; theoretical calculations; volatile anesthetics; Introduction Quantitative structure–activity relationship (QSAR) studies try to find a correlation between chemical

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• the presence of K10 montmorillonite clay forms chiral heterocyclic compounds with the hexahydro-2H-chromene scaffold 2 (Scheme 1) [1][2][3][4]. Products of these reactions are of interest as many of them exhibit a significant analgesic activity in vivo [2][3][4]. In terms of structure–activity

• relationship studies of hexahydro-2H-chromenes and similar compounds it is important to replace the hydroxy group at the C(5) position by another functional group. Thus, the approaches for synthesis of thio- [5] and nitrogen [6] containing analogous with reasonable yields (50−80%) by using a third component

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• analogues on the mobilization of Ca2+ ions. To date, such structure-activity relationship has only been poorly investigated [38][39][40][41]. We anticipate here that compounds 3 and 4 induce the same effect on Ca2+ mobilization in NGF-differentiated PC12 cells. In particular, both compounds produced a

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• 4 – density functional theory (DFT) calculations at UB3LYP/6-31+G(d,p) level, applied to explain the structure–activity relationship. Dimers showed 2–2.5-fold higher values of kA than their monomers. Model 2 gives information about the effects of the side chains and revealed much higher antioxidant

• – ORAC, which measures the scavenging activity against peroxyl radicals generated by an azoinitiator; and model 4 – a theoretical method used for predicting the activity of the studied compounds to scavenge free radicals by H-atom abstraction and to explain the structure–activity relationship of the

• results only in aprotic media. Comparative analysis of the results obtained by using different models and structure–activity relationship The initiated oxidation of a model hydrocarbon substrate (model 1) has an advantage that in this system the rate of initiation (RIN) is well controlled (constant value

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• structure–activity relationship study with several isomeric oxadiazoles. The regioisomeric substitution around the 1,2,4-oxadiazoles (F [22][23] vs G [23][24]) plays a role in the inhibition observed with the glucosyl group at the 5-position of the 1,2,4-oxadiazole ring being preferred. Isomeric 1,3,4

• . The structure–activity relationship of 5-aryl-1,2,4-oxadiazoles F and G towards GP inhibition highlighted a set of interactions of the aryl moieties with the enzyme’s β-channel [22][23][24]. The amino acids present in this empty pocket are of mixed character and can accommodate hydrophobic groups such

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• described. Keywords: angiogenesis; natural phenolic compounds; structure–activity relationship; synthesis; Introduction The term angiogenesis is commonly used to describe the biological process of blood vessel growth. Nevertheless, it should be more precisely defined as the formation of new blood vessels

• show in vitro anti-angiogenic activity with respect to Pazopanib in both HUVEC tube formation assay and the rat thoracic aorta ring test. They inhibited protein kinase B/Akt and ABL tyrosine kinase in the micromolar range. The preliminary structure–activity relationship is summarized in Figure 5. The

• , this compound showed only weak activity during the proliferation assay (IC50 = 53.8 ± 0.3 µM) and did not inhibit tube formation. A basic structure–activity relationship of the aliphatic mono- and bicyclic acylphloroglucinol derivatives with short acyl side chains indicates that the in vitro

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• backbone modifications for bioactive oligonucleotide analogues. These considerations have led to our recently reported design of a novel artificial internucleotide linkage named 'NAA-modification' (Figure 1) [38]. Ongoing synthetic and structure-activity relationship (SAR) studies on naturally occurring

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• provided close to 20 hormaomycin analogues that have contributed to an understanding of the biosynthetic pathways, the conformational behavior in solution and the structure–activity relationship. After the initial observation that hormaomycin (1) has a marked influence on the secondary metabolite