John Martin Clough

Understanding the strobilurin fungicides

Dave W. Bartlett, John M. Clough, Chris R. A. Godfrey, Jeremy R. Godwin, Alison A. Hall, Steve P. Heaney and Steve J. Maund from Syngenta at Jealotts Hill International Research Centre discuss the biology, ecology and resistance management of the strobilurins, especially picoxystrobin, the latest member of the class.

Transition metal mediated organic synthesis: the synthesis of moracin M

Abstract The Palladium catalysed cross coupling of 2-halo- or metallo-benzofurans with both 5-metallo- or halo-resorcinol tricarbonyl chromium(O) complexes and the uncomplexed resorcinols, has been evaluated and in consequence, moracin M has been synthesised in good yield by the cross coupling of 6-(t-butyldiphenylsiloxy)-2-trimethylstannylbenzofuran with 5-iodoresorcinolbis(triisopropylsilyl) ether and fluoride ion deprotection of the product.

Radical cyclisations of propargyl bromoamides and propargyl bromoesters. New routes to tetramic acids, pyrrolinones, tetronic acids and butenolides

Abstract Radical cyclisations of the propargyl bromoamides (5) and (9), and the propargyl bromoesters (17) and (21 a - e ), produce precursors viz (6), (10), (18) and (22), to the tetramic acids (8) and (12), the pyrrolinones (7) and (11), the tetronic acids (20) and (23), and the butenolides (19) and 24), in high overall yields.

Synthesis and Antifungal Activity of Novel Sclerotiorin Analogues

Sclerotiorin 1, first isolated from Penicillium sclerotiorum, has weak antifungal activity and belongs to the azaphilone-type family of natural products. Several series of sclerotiorin analogues were designed and synthesized with the aim of discovering novel fungicides with improved activity. The syntheses involved two key steps, cycloisomerization and then oxidation, and used a simple and efficient Sonogashira cross-coupling reaction to construct the required functionalized precursor. With sclerotiorin as a control, the activities of the newly synthesized analogues were evaluated against seven fungal pathogens, and several promising candidates (compounds 3a₁, 3d₂, 3e₂, 3f₂ and 3k₂) with greater activity and simpler structures than sclerotiorin were discovered. In addition, preliminary structure-activity relationships were studied, which revealed that not only the chlorine or bromine substituent at the 5-position of the nucleus but also the phenyl group at the 3-position and the substituent pattern on it contributed crucially to the observed antifungal activity. Analogues with a methyl substituent at the 1-position have reduced levels of activity, while those with a free hydroxyl group in place of acetoxy at the quaternary center of the bicyclic ring system retain activity.

Stereocontrolled syntheses of strobilurin a and its (9E)-isomer

Abstract The ( E , Z , E )-configuration (1) of the strobilurins has been confirmed by stereocontrolled synthesis.

Transition metal directed synthesis of moracin M, a phytoalexin of Morus alba Linn.

Abstract 2-(5-Resorcinyl)benzofurans have been synthesised by the palladium catalysed cross coupling of 2-trimethylstannyl-or 2-bromozinc benzofurans with the appropriately functionalised 5-iodoresorcinols. These were synthesised by the tri-isopropylsilyloxy directed remote (C-5) lithiation/iodination of the O,O-di(tri-isopropylsilyl)resorcinoltricarbonylchromium(0) complex. The method was applied to the synthesis of moracin M a phytoalexin of Morus alba Linn.

Transition metal mediated synthesis of some prenylated phytoalexins of Morus alba linn.

Abstract Directed functionalisation of resorcinol and benzofuran rings was achieved by activation with a coordinated tricarbonylchromium(0) unit and vicinal or remote lithiation directed by methoxy or t-butyldiphenylsilyloxy groups respectively. The process was applied either before [to the geranylbenzofuran (16) for mulberrofuran B (5)] or after [for moracin C (2)] palladium catalysed coupling of the 2-stannylated benzofuran and the 5-iodinated resorcinol moieties. In addition moracin I (4) was synthesised by a Stille coupling of the stannylated benzofuran (6) with the phloroglucinol triflate (14). Application to the synthesis of albafuran A (3) gave, unexpectedly, the 3-geranylbenzofuran (11).

Synthesis and fungicidal activity of novel pimprinine analogues

A simple and efficient synthetic protocol for 5-(3-indolyl)-oxazoles has been developed and further used to synthesize a series of novel analogues of natural product pimprinine. All new compounds were identified by (1)H NMR, high resolution mass spectrometry, and the structures of 10 and 18o were further confirmed by X-ray crystallographic diffraction analysis. Bioassay conducted at Syngenta showed that several of the synthesized compounds exhibited fungicidal activity. Compounds 10, 17, 18 h, 18o, 19 h, 19i and 19 l all showed effective control of three out of the seven tested phytopathogenic fungi at the highest rate screened. Compounds 17 and 19 h in particular showed activity against the four pathogens screened in artificial media; Pythium dissimile, Alternaria solani, Botryotinia fuckeliana and Gibberella zeae.

Further Daphniphyllum Alkaloids with Insecticidal Activity from the Bark of Daphniphyllum macropodum MIQ.

Two new Daphniphyllum alkaloids, macropodumines J and K (1 and 2, resp.), together with six known structurally related alkaloids, 3–8, were isolated from the bark of Daphniphyllum macropodum Miq. The structures of the new compounds 1 and 2 were elucidated on the basis of a comprehensive analysis of their spectroscopic and chemical data. Macropodumine J (1) contains a CN group which is relatively rare in naturally occurring alkaloids. All isolated compounds were tested for their insecticidal activities against a number of insect species. Daphtenidine C (5) is the most active compound against Plutella xylostella. This is the first report of insecticidal properties of Daphniphyllum alkaloids.

Reactions of 2-acylbenzoates with dimethyloxosulphonium methylide: A novel route to isocoumarins

Abstract Treatment of 2-benzoylbenzoates with dimethyloxosulphonium methylide (1) gives 4-phenylisocoumarins (2); methyl 2-acetylbenzoate gives 4-methylene-3,4-dihydroisocoumarin (3) under the same conditions.