A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF3x OEt2 and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.

The synthesis and subsequent discovery of fungicidally active a-hydroxyarylacetamides originated from a report that phenyltartronic acid amides exhibited insecticidal activity.1 The slow-acting nature of this activity led us to speculate that these compounds might be metabolically activated via hydrolysis and then decarboxylation of one of the amide moieties. Subsequently, a synthesis programme looking at a wide range of ahydroxy-arylacetamides was instigated. This yielded, not a new insecticide, but a novel class of fungicidally active compounds of which compound 1 (Fig. 1) was an early example.2,3 A systematic study of the optimal substitution patterns in the two phenyl rings indicated that, while various electron-withdrawing groups in the 4-or 3,4-position of the mandelic acid ring gave good activity, very little change was allowed in the phenethylamine ring. One of the best analogues was compound 3 * To whom correspondence should be addressed which showed very good activity ([95% control at 50 mg litre~1) against both vine downy mildew (Plasmopara viticola Berl. & De Toni) and potato late blight (Phytophthora infestans (Mont.) de Bary.During the next stage of our optimisation studies we systematically sought to modify the bridge connecting the two phenyl rings. This work resulted in the discovery of the biologically interesting methyl-substituted analogues 4 and 5. The phenylisopropylamide 5 showed the best overall activity seen to date, and we were keen to investigate whether or not there was any biological discrimination between the four stereoisomers. The isomers were separated using chiral HPLC and the highest activity with respect to late blight was found to be associated with the two isomers possessing the RconÐguration at the phenylisopropylamide centre (Table 1). This suggests that, for this pathogen, this chiral centre is biologically more important than that associated with the mandelamide end of the molecule. The absolute conÐguration of the phenylisopropylamine was assigned via an asymmetric synthesis.4The two aryl groups of the a-hydroxyarylacetamide structure are joined by six bonds, of which only one, the amide bond, has any conformational restriction on rotation. When such a non-rigid molecule binds at an enzyme or receptor there is an entropy penalty which must be paid in terms of lowered binding affinity due to loss of free rotation. Consequently, reducing the number of free rotations, for example by introducing a double bond into a chain, can lead to an increased binding affinity at the molecular site of action.5 The preferred conformations of our compounds were studied using 331 1997 SCI. Pestic. Sci. 0031-613X/97/$17.50. Printed in Great Britain (

Pyrazine nucleosides were prepared by condensation of acylglycosyl halides with trirnethylsilyloxypyrazines in benzene i n the presence of si her pe rc hl orate. Reaction of 2,3,4,6 -tetra -0 -acet \/ la-Dg I ucopyra nosy l bromide (1 ) with 2,3-bis(trimethylsilyloxy) pyrazine (2) gave 1.4-dihydro-I ,4-bis-(2,3,4,6-tetra-0-acetyl-@-~-glucopyranosyl)pyrazine-2,3-dione ( 3 ) . Similar reactions of 2,3.5-tri-O-benzoyl-~-ribofuranosyl chloride (4) with the pyrazine ( 2 j and 1 -benzyl-3-trirnethylsilyloxypyrazine-2(1H)-one ( I 4) afforded 1,4-dihydro-l,4-bis-($-~ribofuranosyl)pyrazine-2,3-dione (6) and 1 -benzyl-l,4-dihydro-4-(~-~-ribofuranosyl)pyrazine-2,3-dione (1 6). respectively, via their 2'.3',5'-tri-O-benzoates [ ( 5) and (1 5)]. 1 -Benzyl-l,4-dihydropyrazine-2,3-dione (1 2) w a s prepared by acid-catalysed cyclization of N-benzyl-N'-(2,2-dimethoxyethyl)oxamide ( 9), which w a s obtained by condensation of ethyl N-(2,2-dimethoxyethyl)oxamate (7) with benzylamine.of Chemistry, Queen Elizabeth College, Campden Hill Road, London W8 7AH PVRAZINE nucleosides are analogues of the naturally occurring pyrimidine nucleosides. Under certain conditions unnatural nucleosides may bc incorporated into RNA which will block cell division and growth. Such nucleosides are potential anti-tumour agents since tumour cells metabolize faster than normal cells and tend to incorporate antagonistic compounds prefer-entia1ly.l In attempts to synthesize a pyrazine analogue (17) of uridine, we have isolated the pyrazine nucleosides (6) and ( 16), which gave negative results when tested against Ridgeway osteogenic sarcoma and L.1210.2 showed that direct glucosidation of the silver or mercury salt of pyrazine-2 (1H) -one furnished the O-glucoside and

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Pyruvaldehyde reacts with heterocyclic ureas 4a‐d giving dihydroxyimidazolidin‐2‐ones 5a‐d. Phenyl glyoxal reacts with 4a giving an analogous adduct 5e. These 1,2‐diols are smoothly dehydrated to hydantoins 9a‐e which on mild reduction provide monohydroxyimidazolidin‐2‐ones 10a‐e. Cis and trans isomers of 10d have been isolated and observed to epimerise under suitable conditions. An unusual halogenation converts 5a to the bromomethyl derivative 14b which is a convenient starting material for the synthesis of 4‐substituted imidazolin‐2‐ones such as 15, 16, 17, 18 and 19.

The conversion of the 5‐bromoimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole Ib to the 5‐cyano derivative Ic is firstly described. The 5‐nitroimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole Id is smoothly reduced by aluminium amalgam to the 5‐imino‐5, 6‐dihydroimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole II. However, reaction of Id with sodium dithionite unexpectedly gives 1, 3, 4‐thiadiazoles III and V depending upon conditions.

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