Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• conclusion is consistent with our previous bioinformatic prediction that suggested the presence of genes necessary for the supply of hydroxymalonyl-ACP adjacent to the PKS gene cluster of the butyrolactol biosynthesis. The results obtained in this study provide useful information for further biosynthetic

Self-optimisation and model-based design of experiments for developing a C–H activation flow process

• Alexander Echtermeyer,
• Yehia Amar,
• Jacek Zakrzewski and
• Alexei Lapkin

Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18

• a weak influence of k1,ref and Ea,1 on the model output, i.e., this cannot be estimated with precision. However, this was not necessary, as the parameters do not change the model prediction. Therefore, also the very large 95% confidence interval can be explained. For all other parameters, the

• experiments were conducted, four for each of the two parameter types (shown in Supporting Information File 1). Despite the remaining uncertainty in some of the parameters, indicated by the large 95% confidence intervals, the quality of model prediction was considered to be good-enough for the purpose of in

• convergence, since it is exploring the reaction space to develop a better statistical model. The physical experiments performed thereafter confirmed prediction of the successfully attained target values. Hence, only the successful predicted experimental conditions Xopt were tested in real experiments, which

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• prediction of the gel forming ability of a given molecule is still a formidable challenge, if not altogether impossible [7][8]. Often, the discovery of new gelators relies on an empirical approach wherein structural components capable of forming non-covalent interactions are incorporated into different

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

• -isoxazolidin isoindolinone scaffold in the receptor/ligand complex was difficult because of the open and lipophilic nature of the p53 binding site on MDM2. Therefore, prediction of the possible binding mode was based on two energy types, i.e., the lowest binding energy of the largest cluster and the

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

• methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. Keywords: ADME; computer-aided drug design; docking; free energy; high-throughput screening; LBDD; lead optimization

• structure prediction tools that are routinely used in structure-based drug discovery, widely used docking algorithms, scoring functions, virtual high-throughput screening, lead optimization and methods of assessment of ADME properties of drugs. Review Structure-based drug discovery (SBDD) If the three

• where the target structure is not possible to be determined by experimental methods, computational methods become useful. Determining structures from sequences using computational methods is a powerful tool that can bridge the sequence–structure gap. Importance of protein structure prediction methods

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• verify the prediction is therefore gratifying and demonstrates that the method is indeed a useful tool in discovering new ways to assemble known rings. Following from the preceding discussion about synthesizing odd-membered rings, the Glorius, Shen, and Stonehouse examples involve redox chemistries in

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• -diphenyl-2-picrylhydrazyl radical (DPPH) the spontaneous radical formation could also be observed by the naked eye. Furthermore, the copolymerization parameters of MLA with styrene and MMA were obtained and the Q and e values calculated. The latter allows the prediction of the copolymerization process with

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• in a cis-AT PKS is well-precedented [45][46][47]. The bioinformatic prediction of the configuration at each of the seven asymmetric centres was also in accord with the configuration of authentic ebelactone confirmed by total synthesis [48] (Scheme 1). The essentially complete congruence between

• prediction and the known ebelactone structure means, unless the clone sequenced here under the reference number ATCC 31860 is different from that previously analysed under this same ATCC number [37], that the previous proposal of iteration may have been based on mis-assembly of the DNA sequence due to the

• optional mono- or dimethylation of azalomycin at the guanidino group, and the attachment of a malonyl sidechain at either C-23 or C-25 (Figure 1). No methyltransferase or discrete malonyltransferase is encoded within the respective BGCs. Comparison of the bioinformatic prediction for either marginolactone

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• -lactams 63 (Scheme 16) [95], which is in accordance with the general prediction. The exclusive regioselectivity of this reaction is due to steric effects. Similar conclusions result from the reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66, giving proximal isomer 67 (Scheme 17) [85

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

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• , contain several methyl groups, and possibly one or more olefinic double bonds, an alcohol or ether function. Their much higher structural complexity compared to, e.g., FAMEs and monoterpenes renders a prediction of the fragmentation behaviour of unknown compounds in mass spectrometry and consequently the

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• dimer in the crystal lattice, which is stabilized by two hydrogen bonds between the urea oxygen atoms and the tosyl-protected nitrogens. This also unambiguously confirms the absolute configuration of 39 and corroborates our prediction of the asymmetric adduct 31. We then attempted the installation of

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

• stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then

• structure indeed encodes biochemical properties and that MIA descriptors can be useful to anticipating pMAC of prospective congeneric drug-like candidates. MIA-QSAR and 3D-QSAR have already been compared to each other in a variety of studies and the prediction results are similar [10][24][25][26], but the

• available in the Dragon software. Thus, a major goal in QSAR is to determine and interpret the chemical motifs/properties responsible for the observed biological effects. We have checked that even the simple log P model yields good prediction ability upon selection of test set compounds using the Kennard

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• stable (10–16 kcal/mol) than the primary products, and once formed, they will probably not tautomerize back to 7 and 8. Interestingly, the primary products are of quite similar stability (16.4 to 18.2 kcal/mol, respectively), which does not allow a prediction of which path may dominate the

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• competition gives the computationalists a unique opportunity to try and hone their skills, which in return provides feedback to those interested in the a priori prediction of the thermodynamics of binding. For example, being able to predict ahead of time which ligands binds best to a protein binding-site has

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

• . Similarly, H-13 unveiled the same interactions with H-1 and H-9 while H-14 correlated with H-8 (Figure 4). In order to determine the absolute configuration of the compounds 1–3, ECD spectra prediction was used [36][37]. The absolute configuration of 1 was assigned as 2R, 6S, 7R, 10R, and 11S by ECD analysis

Correction: Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 608–610, doi:10.3762/bjoc.12.59

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• mainly in the s-trans conformation, that factor is crucial since complete prediction of the stereochemical outcome of the reaction is possible. Generally, the enamines formed can interact with the substrates in two ways, via electronic or steric interactions (Scheme 2). The electronic interaction

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• experimentally known MIC values of eight linezolid analogues were used in order to crosscheck the robustness of our model. In a final step, this benchmarking led to the prediction of several new and promising lead compounds. Synthesis and biological evaluation of the new compounds are on the way. Keywords

• ) virtual screenings [28][29][30] of large molecular databases to B) sophisticated simulations of the state equations [31][32]. Nevertheless, both strategies have their own advantages and disadvantages when it comes to the reliable prediction of new drug candidates. While fast virtual screening methods

• calculated relative binding energy of −15.6 kJ/mol seems to be lower bound for the prediction of an effective binder. The experimental ineffectiveness of compound 3 (MIC value >50 mg/L) is mirrored by our computed decrease of the enthalpic contribution by more than 12 kJ/mol. Two earlier in silico approaches

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• to bring together world leading researchers and junior scientists on an equal footing and to provide an environment where research ideas can be openly discussed in order to establish new collaborations and develop new ideas. The future “Prediction is very difficult, especially if it's about the

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• rearranged product. In addition, the dynamics calculations indicated that the 1,2-methyl (C17) shift that forms the abietadiene precursor should occur specifically to one face of the carbocation carbon (C15), a prediction that could be tested through substrate labeling. If only trajectories that lead to the

• than others. Of particular note was the prediction that the TSS for conversion of the cedryl cation to the prezizyl cation (Figure 11, step 9) and for the conversion of the prezizyl cation to the zizyl cation (Figure 11, step 10) are bound more strongly than the carbocations that immediately precede

My maize and blue brick road to physical organic chemistry in materials

• Anne J. McNeil

Beilstein J. Org. Chem. 2016, 12, 229–238, doi:10.3762/bjoc.12.24

• gelators. To test this hypothesis, we used crystal morphology prediction tools to identify needle-shaped crystals in the CSD. Graduate student Kelsey (King) Carter and undergraduate student Sarah Cox predicted the morphologies of 186 Pb(II)-containing crystals. Focusing on the top 5% and selecting stable

• additional compounds were synthesized, all of which were gelators, with some exhibiting lower cgcs than the known gelators (Scheme 1b). Given the mixed results of this approach, we believe that our CSD-morpholgy prediction method represents a better strategy for identifying new gelators for specific

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• experimental PXRD trace of the product with that of an isostructural inclusion complex, namely the β-CD complex of 4-tert-butylbenzyl alcohol (CSD refcode KOFJEU [16]), and finding a reasonable match [20]. This procedure also enabled correct prediction of the space group (C2221) of the complex and the

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• The gas phase energy, ΔEMM, is a summation of bonded and non-bonded (electrostatic and van der Waals (vdW)) energies obtained from molecular mechanics calculation. The ΔGsolv is solvation free energy. In general, there are several methods for ΔGsolv prediction. Some methods calculate the ΔGsolv using

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• synthesis of fused bicyclic hydantoins. 1H NMR spectroscopy monitoring, as well as 1H NMR chemical shifts prediction [29][30][31][32][33][34] is used as a useful tool in the search of the most probable intermediates in the reaction. The theoretical results are discussed and compared with our experimental