Applying the Crystalline Sponge Method to Agrochemicals: Obtaining X-ray Structures of the Fungicide Metalaxyl-M and Herbicide -Metolachlor.

The crystalline sponge method is a technique that provides the ability to elucidate the absolute structure of noncrystalline or hard to crystallize compounds through single-crystal X-ray diffraction by removing the need to obtain crystals of the target compound. In this study the crystalline sponges {[(ZnX)(2,4,6-tris(4-pyridyl)-1,3,5-trazine)].(solvent)} (X = I, Br) were used to obtain X-ray structures of the agrochemical active ingredients metalaxyl-M and S-metolachlor.

Investigating discrepancies between experimental solid-state NMR and GIPAW calculation: NC-N C and OH⋯O H chemical shifts in pyridinium fumarates and their cocrystals.

An NMR crystallography analysis is presented for four solid-state structures of pyridine fumarates and their cocrystals, using crystal structures deposited in the Cambridge Crystallographic Data Centre, CCDC. Experimental one-dimensional one-pulse H and C cross-polarisation (CP) magic-angle spinning (MAS) nuclear magnetic resonance (NMR) and two-dimensional N-H heteronuclear multiple-quantum coherence MAS NMR spectra are compared with gauge-including projector augmented wave (GIPAW) calculations of the H and C chemical shifts and the N shifts that additionally depend on the quadrupolar interaction. Considering the high ppm (>10 ​ppm) H resonances, while there is good agreement (within 0.

5-amino-2-methylpyridinium hydrogen fumarate: An XRD and NMR crystallography analysis.

Single-crystal X-ray diffraction structures of the 5-amino-2-methylpyridinium hydrogen fumarate salt have been solved at 150 and 300 K (CCDC 1952142 and 1952143). A base-acid-base-acid ring is formed through pyridinium-carboxylate and amine-carboxylate hydrogen bonds that hold together chains formed from hydrogen-bonded hydrogen fumarate ions. H and C chemical shifts as well as N shifts that additionally depend on the quadrupolar interaction are determined by experimental magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) and gauge-including projector-augmented wave (GIPAW) calculation.

A new approach to the optimisation of non-uniform sampling schedules for use in the rapid acquisition of 2D NMR spectra of small molecules.

Non-uniform sampling allows the routine, rapid acquisition of 2D NMR data. When the number of points in the NUS schedule is low, the quality of the data obtained is very dependent of the schedule used. A simple proceedure for finding optimium schedules has been developed and is demonstrated for the multiplicity edited HSQC experiment.

NMR quantification using an artificial signal.

We have developed QUANTAS (QUANTification by Artificial Signal), which is a software-based protocol for concentration measurement by NMR. QUANTAS is an absolute intensity external standard method for quantification by NMR that compensates for various experimental parameters. It is applicable to all nuclei and modern spectrometers.

Biosynthesis of the putative siderophore erythrochelin requires unprecedented crosstalk between separate nonribosomal peptide gene clusters.

The genome of the erythromycin-producing bacterium Saccharopolyspora erythraea contains many orphan secondary metabolite gene clusters including two (nrps3 and nrps5) predicted to govern biosynthesis of nonribosomal peptide-based siderophores. We report here the production by S. erythraea, even under iron-sufficient conditions, of a 2,5-diketopiperazine siderophore candidate we have named erythrochelin.

Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach.

Many years of work have been invested in the identification of potent and selective COX-2 inhibitors for the treatment of chronic inflammatory pain. One issue faced by workers is the balance between the lipophilicity required for potent enzyme inhibition and the physical properties necessary for drug absorption and distribution in vivo. Frequently approaches to reduce lipophilicity through introduction of polar functionality is hampered by highly challenging chemistry to prepare key molecules.

Fast 1H-13C correlation data for use in automatic structure confirmation of small organic compounds.

A method of speeding up the acquisition of 1H-13C correlation data has been developed. It is applicable in situations where the experiment time is determined by the need to sample the second dimension adequately rather than by signal-to-noise ratio requirements. Two spectra with different, reduced, 13C sweep widths are measured, time being saved by reducing the number of increments in line with the reduction in the sweep width.

Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor.

The calcium-dependent antibiotic (CDA), from Streptomyces coelicolor, is an acidic lipopeptide comprising an N-terminal 2,3-epoxyhexanoyl fatty acid side chain and several nonproteinogenic amino acid residues. S. coelicolor grown on solid media was shown to produce several previously uncharacterized peptides with C-terminal Z-dehydrotryptophan residues.

Three new pyridoacridine type alkaloids from a singaporean ascidian.

Two new pyridoacridine alkaloids, kuanoniamines E and F, and a new ring-opened pyridoacridine alkaloid, subarine, were isolated from a Singaporean ascidian. Also isolated were known pyridoacridine alkaloids ascididemin and kuanoniamines A and D. The structures of the alkaloids were determined by spectroscopic methods.

Engineered urdamycin glycosyltransferases are broadened and altered in substrate specificity.

Combinatorial biosynthesis is a promising technique used to provide modified natural products for drug development. To enzymatically bridge the gap between what is possible in aglycon biosynthesis and sugar derivatization, glycosyltransferases are the tools of choice. To overcome limitations set by their intrinsic specificities, we have genetically engineered the protein regions governing nucleotide sugar and acceptor substrate specificities of two urdamycin deoxysugar glycosyltransferases, UrdGT1b and UrdGT1c.

The production of novel sordarin analogues by biotransformation.

The biotransformation of the fungal protein synthesis inhibitor sordarin is reported. Nine taxonomically diverse organisms supported the isolation and identification of twelve modified products. The structural diversity of the biotransformation products observed and their value in supporting further chemistry is discussed.

A rapid and facile method for the dereplication of purified natural products.

A new approach to the use of commercial databases for the dereplication of purified natural products has been developed. This is based on searching a text file that links each structure with its molecular weight and an exact count of the number of methyl, methylene, and methine groups it contains. Analysis of such a text file, constructed from a database containing more than 126,000 natural product structures, revealed that these data, readily measured using MS and NMR spectroscopy, are highly discriminating.

Engineering a polyketide with a longer chain by insertion of an extra module into the erythromycin-producing polyketide synthase.

Background: Modular polyketide synthases catalyse the biosynthesis of medically useful natural products by stepwise chain assembly, with each module of enzyme activities catalysing a separate cycle of polyketide chain extension. Domain swapping between polyketide synthases leads to hybrid multienzymes that yield novel polyketides in a more or less predictable way. No experiments have so far been reported which attempt to enlarge a polyketide synthase by interpolating additional modules.

Circumdatin G, a new alkaloid from the fungus Aspergillus ochraceus.

The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G.

Discovery of novel ansamycins possessing potent inhibitory activity in a cell-based oncostatin M signalling assay.

We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout.

Eryloside F, a novel penasterol disaccharide possessing potent thrombin receptor antagonist activity.

We report the discovery of Eryloside F, a novel disaccharide of the steroidal carboxylic acid penasterol, isolated from an extract of the marine sponge Erylus formosus. The compound is a potent thrombin receptor antagonist, and furthermore inhibits human platelet aggregation in vitro.

Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase.

Background: The macrolide antibiotic erythromycin A, like other complex aliphatic polyketides, is synthesised by a bacterial modular polyketide synthase (PKS). Such PKSs, in contrast to other fatty acid and polyketide synthases which work iteratively, contain a separate set or module of enzyme activities for each successive cycle of polyketide chain extension, and the number and type of modules together determine the structure of the polyketide product. Thus, the six extension modules of the erythromycin PKS (DEBS) together catalyse the production of the specific heptaketide 6-deoxyerythronolide B.

Isolation and characterisation of a prenylated p-terphenyl metabolite of Aspergillus candidus possessing potent and selective cytotoxic activity; studies on mechanism of action.

We describe the discovery and properties of a prenylated p-terphenyl metabolite of the fungus Aspergillus candidus. The compound (1) possesses potent cytotoxic activity against a range of tumour and other hyper-proliferative cell lines. Cell cycle analysis shows that in mouse keratinocyte (BALB/MK) cells treated with 1, the cell cycle is arrested in early S phase, indicative of an antimetabolite effect.