John N. Bilton

An x-ray crystallographic, mass spectroscopic, and NMR study of the limonoid insect antifeedant azadirachtin and related derivatives

Abstract The limonoid insect antifeedant azadirachtin (1) may be partially hydrogenated at the C22-C23 position and subsequently treated with an excess of sodium periodate and potassium permanganate in the presence of a base to give detigloyldihydroazadirachtin (4). This compound was examined by X-ray crystallographic techniques which revealed key structural fragments and together with detailed n.m.r. and mass spectroscopic studies allowed the complete unambiguous structure assignment to the parent azadirachtin molecule. Two further compounds, 3-deacetyl-11-desoxyazadirachtin (2), and 3-acetoxy-7-tigloyl-vilasinin lactone (3) were also isolated and characterised from a Senegal sample of neem seed.

Chickpea blight: Production of the phytotoxins solanapyrones A and C by Ascochyta rabiei

Abstract Filtrates from 12-day-old stationary cultures of Ascochyta rabiei grown on Czapek-Dox medium, supplemented with an extract of chickpea seed, killed the cells in cell suspensions obtained by enzymic digestion of chickpea leaflets. Two toxins were isolated by solvent partitioning with ethyl acetate and flash chromatography of the organic fraction on silica. Mass spectrometry, UV, 13 C/ 1 H NMR and X-ray analysis showed that the two compounds were identical to the phytotoxins solanapyrones A and C isolated previously from culture filtrates of the fungus Alternaria solani .

Janthitrems B and C, two principal indole-diterpenoids produced by Penicillium janthinellum

Abstract The structures of janthitrems B and C, the two most abundant tremorgenic mycotoxins produced by certain isolates of Penicillium janthinellum from New Zealand and Australia, have been elucidated by NMR spectroscopy. The compounds differ only by the oxygen atom in janthitrem B at C-22 but closely resemble janthitrems E-F except for dehydration in the terminal isoprene of the diterpenoid moiety. The diterpenoid moiety of janthitrems B and C is identical to that of penitrem D and generally similar to that of all penitrems.

Chemistry of insect antifeedants from (part 1): Conversion from the azadirachtin to the azadirachtinin skeletons

Abstract The conversion of azadirachtin derivatives to the corresponding azadirachtinin skeletons can be achieved in high yield under mild conditions.

Auranthine, a new benzodiazepinone metabolite of Penicillium aurantiogriseum

A novel metabolite, auranthine, has been isolated from sporing cultures of Penicillium aurantiogriseum and its structure, 6,7,7a,8-tetrahydroquinazolino[3′,2′:1,6]pyrido[2,3-b][1,4]benzodiazepine-9,16-dione comprising anthranilate and glutamine moieties, has been elucidated from spectral evidence and biosynthetic reasoning.

Structural reappraisal of the limonoid insect antifeedant azadirachtin

Based upon a detailed 250 MHz 1H n.m.r. study an alternative structure for the limonoid antifeedant azadirachtin has been determined.

Glyantrypine, a novel anthranilic acid-containing metabolite of Aspergillus clavatus

The structure of a novel indole alkaloid, glyantrypine 2, a main secondary metabolite of Aspergillus clavatus has been elucidated by biosynthetic evidence, mass spectrometry and 1H and 13C NMR techniques. The compound extends the variety of metabolites biosynthesised from anthranilic acid and tryptophan without forming a benzodiazepine.

Oxidative transformation of paxilline in sheep bile.

1. 14C-Paxilline incubated in bile from pasture-fed sheep was efficiently transformed to a more polar dioxygenated derivative in which the indole 2,3 double-bond had opened to give an 8-membered ring. The structure is proposed on the basis of mass spectrometry and 1H- and 13C-n.m.r. spectroscopy. The new compound is 2,18-dioxo-2,18-seco-paxilline. 2. The paxilline transformation also occurred in bile which had been boiled to inactive enzymes. 3. The dissolved oxygen concentration in freshly collected sheep bile was in the range 38-163 nmol/ml. 4. Whereas paxilline causes pronounced tremor in the mouse given 4 mg/kg i.p., the dioxygenated paxilline was biologically inactive at ten times this dose. 5. The feasibility that analogous oxidative transformation of indole-diterpenoid tremorgenic mycotoxins may occur, increasing polarity advantageously to xenobiotic elimination, during biliary elimination from agricultural ruminants in the field, is recognized. Concomitant loss of tremorgenicity is an additional benefit. 6. The biotransformation of paxilline in sheep bile was mimicked by ozonolysis but the ozone equivalent 4-t-butyl-iodoxybenzene was not similarly effective.

Pennigritrem, a naturally-occurring penitrem A analogue with novel cyclisation in the diterpenoid moiety

A prominent novel analogue of penitrem A has been resolved from the tremorgenic alkaloids of a strain of Penicillium nigricans and the structure, elucidated by NMR spectroscopy, shown to involve the terminal diterpenoid isoprene in a cyclisation which is unique amongst fungal indolediterpenoids. Consequent conformational changes in the biologically active moiety significantly reduced tremorgenicity.