Gordon Shaw

Nucleoside Analogues with a Novel Glycone Based on the Benzo[C]Furan Core

Abstract Routes to novel nucleoside analogues based on 1, 3-dihydrobenzo[c]furan have been investigated. Thus l-(1, 3-dihydro-3-hydroxymethylbenzo[c]furan-1-yl)-thymine, an analogue of d4T, was obtained as two diastereoisomers. The cis compound (quasi β-D/α-L stereochemistry) was obtained pure but the trans compound was only 90% pure. A purine analogue with a four atom spacer group between base and glycone was also prepared. The conformation of these constrained nucleosides was studied by molecular modelling.

Chelating diphosphite complexes of nickel(0) and platinum(0): their remarkable stability and hydrocyanation activity

The synthesis, stability and hydrocyanation catalytic activity of nickel(0) complexes of the diphosphite 1 derived from 2,2′-biphenol are described; the X-ray crystal structures of the ligand 1 and its platinum(0) complex 2b are reported.

The structure and physiological activity of some N6-substituted adenines

Abstract Some 22 N 6 -substituted adenines have been prepared and their biological activity tested, for comparison with zeatin, in an aseptic carrot assay system that measures the growth promoting activity in terms of fresh weight (mg), and the number of cells in thousands [and hence their average weight (μg/cell)] produced in carrot root explants. The test medium contained all the prerequisites for growth and its induction other than the factors which specifically induce growth by cell division and enlargement. In a series of n -alkylaminopurines, where n varied from 1 to 10, the maximum activity occurred with n = 5 and, in this series, the activity was due to the effects upon cell division per se , relatively uncomplicated by effects upon cell enlargement. The activity of compounds with a formal similarity to zeatin varies with the functional groups in the side chain, but more because of their relative tolerance for concomitant cell enlargement than due to the effects of substituent groups on cell division per se . The data contribute to the understanding of the chemical induction of growth, which is essential to interpret growth regulation in plants.

Purines, pyrimidines, and imidazoles. Part XL. A new synthesis of a D-ribofuranosylamine derivative and its use in the synthesis of pyrimidine and imidazole nucleosides

2,3-O-Isopropylidene-D-ribofuranosylamine has been prepared in high yield as the stable crystalline toluene-p-sulphonate by reaction of D-ribopyranosylamine with acetone, 2,2-dimethoxypropane, and toluene-p-sulphonic acid. The anomeric configuration of the furanosylamine in various solvents has been investigated by n.m.r. spectroscopy and optical rotation measurements. In chloroform the β-form predominates whereas in dimethyl sulphoxide a high proportion of the α-form is present. A bis(isopropylideneribofuranosyl)amine of unknown anomeric configuration has also been prepared from the furanosylamine toluene-p-sulphonate; this has also been obtained as a by-product in some reactions.Reaction of the furanosylamine with several, α-cyano, -acetyl, or -ethoxycarbonyl-β-ethoxy-N-ethoxycarbonyl-acrylamides occurs in both aqueous and non-aqueous solutions to give corresponding 5-substituted uracil α- and β-ribofuranosides. Assignments of anomeric configurations were confirmed by n.m.r. spectroscopy, by comparison with known compounds, and, in the case of 5-ethoxycarbonyluridine, by hydrolysis to the uridine-5-carboxylic acid and smooth decarboxylation of this to uridine by a new method which has also been used to decarboxylate uracil-5-carboxylic acid and its 1-methyl and 1-phenyl derivatives.The furanosylamine with β-methoxy-α-methylacryloyl isothiocyanate also gave, via an intermediate acyclic thiourea riboside, 2-thiothymine 1-(isopropylidene-β-D-ribofuranoside).Treatment of the furanosylamine either with ethyl N-[alkoxycarbonyl or carbamoyl(cyano)methyl]formimidates, or with ethylformimidate hydrochloride [to give a mixture of ethyl N-(2,3-O-isopropylidene-α- and β-ribofuranosyl)-formimidates], followed by ethyl α-amino(cyano)acetate, gave 5-amino-4-(alkoxycarbonyl or carbamoyl)imidazole isopropylidene-α- and β-ribofuranosides, from which the isopropylidene groups may be removed by aqueous acetic acid. Phosphorylation of the two anomeric esters gave corresponding 5-aminoimidazole-4-carboxylic acid α- and β-ribotides.Structures of the aminoimidazole nucleosides and nucleotides were confirmed by comparisons with known compounds and by use of spectral (especially c.d.) techniques. Rates of reaction of several formimidates and acetimidates with cyclohexylamine have been examined.

A novel stereospecific synthesis of 5-amino-1-β-D-fructofuranosylimidazole-4-carboxamide

A β-D-fructofuranose fused oxazolidine-2-thione has been isolated as the t-butyldimethylsilyl derivative (6), which when desulphurised and treated with α-amino-α-cyanoacetamide gave the silylated 1-β-D-fructofuranosyl aminoimidazole (2b) which when deblocked with methanolic hydrogen chloride produced 5-amino-β-D-fructofuranosyl-imidazole-4-carboxamide (2a).

Genetic Differences in the Enzymatic Regulation of Zeatin Metabolism in Phaseolus Embryos

Hormones play a significant role in all phases of growth and development of higher plants. Although the site(s) of action of hormones are largely unknown, it can be postulated that rather precise regulatory mechanisms must exist to maintain a critical hormone balance in order for controlled development to occur. We have focused our research on cytokinin metabolism in Phaseolus with the objective of identifying genetic mechanisms regulating cytokinin metabolism and biosynthesis. A systematic approach was taken by screening for genetic variations of interest, followed by genetic and biochemical characterizations. This approach has been successfully applied to callus systems and a number of reports describing inter- and intra-specific differences have been published [1, 16, 17, 18, 19, 20, 21, 23]. In this paper we summarize recent findings concerning the genetic differences in zeatin (Z) metabolism occurring in immature Phaseolus embryos. The studies described here have led to the identification of a new Z metabolic pathway and the discovery of differential expression of cytokinin-specific enzymes in Phaseolus.

The biological activity and metabolism of a novel cytokinin metabolite, O-xylosylzeatin, in callus tissue of Phaseolus vulgaris and P. lunatus

Summary The biological activity of the novel zeatin metabolite, O-xylosylzeatin, was examined in two Phaseolus callus bioassays, P. vulgaris cv. Great Northern (GN) and P. lunatus cv. Kingston (K). O-xylosylzeatin was equally active in both systems, but was 100 times more active than zeatin in GN and 10 times less active than zeatin in K tissues. These tissues slowly converted 14C-la-beled O-xylosylzeatin to zeatin, ribosylzeatin, ribosylzeatin 5′-monophosphate, an O-glucosyl derivative of ribosylzeatin, and breakdown products such as adenine, adenosine, and AMP. Incubation with [ 14 C]zeatin gave the same array of metabolites in similar proportions as incubation with O-xylosyl [ 14 C]zeatin. Since the extent of side chain degradation of zeatin was the same in both tissues, the low activity of zeatin in GN seems unrelated to cytokinin oxidase activity and therefore the high activity of O-xylosylzeatin may not be due to resistance against enzymatic attack. The possibility that O-xylosylzeatin itself is cytokinin-active should be considered.

Phosphorylation of Some 5-Aminoimidazole Nucleosides to the 5’ -Phosphates Using a Phosphotransferase from Wheat

Abstract Several D-ribofuranosyl, D-xylofuranosyl and D-arabinofuranosyl 5-aminoimidazoles have been successfully phosphorylated to 5’ -phosphates using a phosphotransferase from wheat shoots and p-nitrophenylphosphate as a phosphate donor.

2-Methoxyphenyl phosphite complexes of platinum(0) and nickel(0)

The compounds P(OC6H4OMe-2)3 and P(OC6H4OMe-2)(OC6H4Me-4)2 have been prepared. The platinum(0) complex [Pt{P(OC6H4OMe-2)3}3]1 can be made by the reduction of [PtCl2{P(OC6H4OMe-2)3}2] in the presence of the phosphite or by addition of the latter to tris(η2-norbornene)platinum, and [Pt(η2-C2H4){P(OC6H4OMe-2)3}2]2 by the reduction of [PtCl2{P(OC6H4OMe-2)3}2] in the presence of ethene or by adding of the phosphite to [Pt(η2-C2H4)3]. The crystal structures of the ligand P(OC6H4OMe-2)3 and complex 2 have been determined and the effect of co-ordination on the conformation of the phosphite substituents is discussed. The ethene ligand in 2 is readily substituted by other alkenes and alkynes to give complexes 3–9 of the general type [Pt(η2-alkene){P(OC6H4OMe-2)3}2] or [Pt(η2-alkyne){P(OC6H4OMe-2)3}2]. Reduction of [Ni(acac)2](acac = acetylacetonate) with AlMe3 in the presence of ethene gives [Ni(η2-C2H4){P(OC6H4OMe-2)3}2]10. The air-sensitive complex [Ni{P(OC6H4OMe-2)3}3]11 can be generated in solution by treatment of [Ni(cod)2](cod = cycloocta-1,5-diene) or 10 with the phosphite ligand. The tetrahedral complex [Ni{P(OC6H4OMe-2)(OC6H4Me-4)2}4]12 is readily made from [Ni(cod)2] and the phosphite. The catalytic activity of 11 and 12 for the monohydrocyanation of buta-1,3-diene is discussed in relation to similar well known catalysts and it is concluded that the methoxy groups inhibit the catalysis probably by a combination of steric hindrance and weak co-ordination of the ether oxygen.

Purines, pyrimidines, and imidazoles. Part 52. New syntheses of some 1-β-D-arabinofuranosylaminoimidazoles and of related purine nucleosides, including 9-β-D-arabinofuranosyladenine

Ethyl 5-amino-1-β-D-arabinofuranosylimidazole-4-carboxylate and the corresponding carboxamide have been prepared by reaction of ethyl 5-aminoimidazole-4-carboxylate or the carboxamide, respectively with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (but not the bromide or iodide) and deblocking. Reaction of the nucleoside ester with formamidine acetate gave 9-β-D-arabinofuranosylhypoxanthine. 5-Amino-4-cyano-1-β-D-arabinofuranosylimidazole obtained by dehydration of the benzylated carboxamide or by direct glycosylation of 5-amino-4-cyanoimidazole and debenzylation of the product, when heated with triethyl orthoformate and ammonia, gave 9-β-D-arabinofuranosyladenine. 2,3,5-Tri-O-benzylarabinofuranosyl chloride with sodium azide, followed by reduction of the glyosyl azide formed with platinic oxide, and condensation of the arabinosylamine produced with ethyl N-(carbamoylcyanomethyl)formimidate gave a mixture of 2,3,5-tri-O-benzyl 1-α- and -β-D-arabinofuranosylimidazole 4-carboxamides. Reduction of the azide with lithium aluminium hydride followed by debenzylation of the product gave, in addition to the two anomers, 5-amino-1-D-arabinitylimidazole-4-carboxamide.