Search

Meeting Programme Dr Nigel Botting [University of St Andrews, UK] – Isotopic Labelling of Lignan Phytoestrogens. Prof. Frederic Dolle [CEA PET Centre, Orsay, France] – Fluorine-18 Chemistry: A Selection of Recent Advances. Prof. Peter Scott [University of Warwick, UK] – Creating Chiral Metal Centres. Mr Laurent Brichard [WBIC, University of Cambridge, UK] – A Simple Device for the Radiosynthesis of [Carbonyl-11C]amides, Esters and Ketones using Carbon-11 Monoxide. Dr Michael Hickey [AstraZeneca Charnwood, UK] – Tritium-labelling via an Iridium-based Solid-phase Catalyst. Prof. Wolfgang Steglich [Ludwig-Maximilians University, Germany] – Meroterpenoids from Mushrooms, A Colourful Group of Natural Products. Dr Joe Schofield [Sanofi-Aventis, France] – Radio- and Stable-isotope Labelling of SSR591813 – A Nicotinic Partial Agonist. Dr Nikolai Kuhnert [University of Surrey, UK] – Chiral Recognition in Ion Trap Mass Spectrometry using Isotopically Labelled Trianglamine Macrocycles. Dr Paul Watts [University of Hull, UK] – The Application of Micro Reactors for Radiochemical Synthesis. Dr Tony Gee [GlaxoSmithKline, UK] – PET in Drug Discovery and Development. Dr Alan Wadsworth [GlaxoSmithKline, UK] – Stable Isotopic Labelling of Heterocyclic Compounds

Reaction of the ethyl 3-arylpyruvate 5a with the methyl 2-bromo-3-arylpyruvate 6b in the presence of the 2-arylethylamine 4 afforded the pyrrole derivative 10, which could be transformed into lamellarin L (1) in five steps. The synthesis proceeds with 38% overall yield and mimics the probable biosynthesis of these marine alkaloids.

A new inhibitor of leukotriene biosynthesis, (+)-10 alpha-hydroxy-4-muurolen-3-one (1), was isolated from fermentations of Favolaschia sp. 87129. Its structure was established by spectroscopic methods. The compound exhibited no antifungal or antibacterial activities. The effects of 1 on leukotriene biosynthesis were compared with (+)-T-cadinol, (-)-3-oxo-T-cadinol, and (+)-3 alpha-hydroxy-T-cadinol, three related sesquiterpenes.

In the course of our search for new biologically active metabolites, lachnellin A (1), a metabolite with high cytotoxic and antimicrobial activities, the structurally related lachnellins B, C and D (3, 4, 7), and naphthalene-1,3,8-triol (8), an inhibitor of malate synthase (EC 4.1.3.2), were isolated from submerged cultures of the ascomycete Lachnellula sp. A 32-89. The antimicrobial, cytotoxic and phytotoxic activities of lachnellin A depended on its reactivity and could be abolished by the addition of cysteine. The enzyme inhibiting activity of (8) was due to reactive intermediates during melanization and was no longer observed in the presence of serum albumin. In addition, rac-scytalone (9), (+)-trans-3,4-dihydro-3,4,8-trihydroxy-1 (2H)-naphthalenone (10), 2,5-dihydroxytoluene (11), and (R)-(-)-5-methylmellein (12) were obtained from the same source and biologically characterized.

In a search for inhibitors of RNA-directed DNA polymerases a new isolactarane sesquiterpenoid, hyphodontal (1), was isolated from fermentations of a Canadian Hyphodontia species. Its structure was elucidated by spectroscopic methods. Hyphodontal strongly inhibits the growth of several yeasts and is a non-competitive inhibitor of avian myeloblastosis virus (Ki 346 μᴍ) and Moloney murine leukemia virus (Ki 112 μᴍ) reverse transcriptases. In addition, cytotoxic and antifungal activities were observed.

A new hirsutane derivative, phellodonic acid (1), has been isolated from fermentations of Phellodon melaleucus strain 87113. Its structure was elucidated by spectroscopic methods. The compound exhibits antibiotic activities towards bacteria and fungi. 1 is the first bioactive metabolite from cultures of a species belonging to the family Thelephoraceae.

Tyromycin A, a new inhibitor of leucine and cysteine aminopeptidases has been isolated from mycelial cultures of the basidiomycete Tyromyces lacteus (Fr.) Murr. Its structure was established as 1,16-bis-[4-methyl-2,5-dioxo-3-furyl]hexadecane (1) by spectral analysis and transformation into ester and imide derivatives.

Omphalone, a new antibiotic, cytotoxic, and phytotoxic pigment has been isolated from fermentations of a Canadian strain of Lentinellus omphalodes. Its structure has been established as 2-(4-methylfuran-2-yl)-1,4-benzoquinone (1) by spectroscopic investigations and conversion into leuco-acetate 2.

A novel enzyme inhibitor of RNA-directed DNA-polymerases of avian myeloblastosis and murine leukemia virus was isolated from fermentations of an tasmanian Podoscypha species. Its structure was elucidated by spectroscopic methods and oxidative degradation as (E)-4,5-dioxo-2-hexadecenoic acid (1). The enzyme inhibitor, which was named podoscyphic acid, did not inhibit DNA and RNA synthesis in permeabilized L 1210 cells nor did it affect RNA synthesis in isolated nuclei of L 1210 cells. 1 inhibits protein synthesis in whole L 1210 cells and rabbit reticulocyte lysate and shows very weak antimicrobial and cytotoxic properties. The testing of ethyl (E)-4,5-dioxo-2-hexadecenoate (2) and (E)-4-oxo-2-tetradecenoic acid (11) revealed the importance of the free gamma-oxoacrylic acid unit for the biological activities of 1.

Strobilurin D and strobilurin F, two new cytostatic and antifungal antibiotics of the (E)-beta-methoxyacrylate class, have been isolated from mycelial cultures of the basidiomycete Cyphellopsis anomala (Pers. ex Fr.) Sing. The structures were elucidated by spectroscopic methods. The antibiotics inhibit the growth of human and animal cells and a wide variety of fungi. Like strobilurins A and B, the new metabolites are potent inhibitors of respiration.

In the structural elucidation of natural products, problems may arise owing to extensive signal overlap and line broadening in the NMR spectra as well as unexpected chemical reactions. This is illustrated in the analysis of some novel compounds isolated from fruit bodies of toadstools and slime moulds, including infractopicrin, lascivol, retipolide A, arcyroxepin A and rubroflavin. In some cases, the problems could be solved by spectroscopic techniques such as two-dimensional INADEQUATE experiments, nuclear Overhauser enhancement measurements or X-ray structural analysis; in other cases, chemical transformations were necessary to resolve the structure.

Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A.

The title esters derived from fluorenylmethoxycarbonyl amino acids undergo transesterification with hydroxymethyl polymers in the presence of tertiary base without racemisation.