Josie C. Briggs

Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C

A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.

(Halogenomethyl)phenyl α-D-glucopyranosides as enzyme-activated irreversible inhibitors of yeast α-glucosidase and potential anti-HIV agents

A range of (halogenomethyl)phenyl α-D-glucopyranosides 2–7, prepared from corresponding methylphenyl glucosides by synthetic manipulation of the aglycone moiety, have been investigated as enzyme-activated irreversible inhibitors of yeast α-glucosidase and their anti-HIV activity measured. Compounds 5–7, which also contain a 4- or 6-nitro group in the phenyl ring of the aglycone, are much more effective inhibitors of the enzyme than are compounds 2–4 which lack this feature.

The synthesis of conformationally-restricted diacyl glycerol analogues

Abstract A series of conformationally-restricted diacylglycerol analogues have been prepared in homochiral form as potential protein kinase C antagonists using D-ribonolactone and D- and L-2-deoxyribose as starting materials.

2-Chloromethyl-4-nitrophenyl α-D-glucopyranoside: an enzyme-activated irreversible inhibitor of yeast α-glucosidase

2-Chloromethyl-4-nitrophenyl α-D-glucopyranoside, prepared by a novel, four-step route from 2-methylphenyl α-D-glucopyranoside tetraacetate, is highly effective as an enzyme-activated irreversible inhibitor of yeast α-glucosidase and is much superior in this respect to 2-chloromethylphenyl α-D-glucopyranoside.

Potassium borohydride reductions of ketones absorbed into polymer supports: stereochemical effects

The proportions of 6α-alcohol obtained from aqueous potassium borohydride reductions of 3β-hydroxy-5α-cholestan-6-one (1) absorbed into various polymers varied from 0 to 90% depending on the polymer used and whether or not a phase transfer catalyst was added; some other ketones show similar stereochemical effects, the greatest effects probably arising when the substrates are adsorbed to the inner surfaces of appropriate polymers.

Notes. Unsymmetrical bis(phosphorus) compounds: synthesis of unsymmetrical ditertiary phosphines, phosphine oxides, and diquaternary phosphonium salts

A convenient preparative route to the unsymmetrical bidentate phosphines R2P(CH2)nPPh2(R = Me or Et; n= 3 or 4) is described. This involves the synthesis of unsymmetrical diphosphonium salts, [R2PhP(CH2)nPPh3]Br2, and diphosphine oxides, R2P(O)(CH2)nPPh2, as intermediates. The symmetrical ligand Et2P(CH2)3PEt2 was also prepared by the same route. New co-ordination complexes of manganese(II) with these ligands have been isolated.

The synthesis and evaluation of diacylglycerol analogues as potential second-messenger antagonists

Abstract Structural analogues of diacylglycerol have been synthesized in an attempt to discover antagonists of protein kinase C with the aim of developing new agents for preventing cell proliferation. Structural analogues of diacylglycerol have been synthesized in an attempt to discover antagonists of protein kinase C with the aim of developing new agents for preventing cell proliferation.

Octahedral and trigonal-bipyramidal complexes of ruthenium(II) with bidentate phosphine ligands

Six- and five-co-ordinate complexes of ruthenium(II) with the unsymmetrical diphosphine ligand Ph2P(CH2)3PMe2 have been prepared. Phosphorus-31 n.m.r. spectroscopy indicates that octahedral complexes [RuCl2(P–P)2], [RuH(Cl)(P–P)2], and [RuH(CO)(P–P)2]ClO4(P–P = diphosphine ligand) have the all-trans arrangement with Me2P trans to Me2P and Ph2P trans to Ph2P. The five-co-ordinate complexes [Rux(P–P)2]BPh4, where X = Cl or H, are not fluxional at room temperature and have a trigonal-bipyramidal structure with axial PMe2 groups and equatorial PPh2 groups. Similar structures are proposed for analogous complexes of Ph2P(CH2)3PMePh and of Ph2P(CH2)3PPh2.

Tertiary phosphine adducts of manganese (II) dihalides. The X-ray crystal structure of di-iodo(phenyldimethylphosphine)manganese(II)

AnX-Crystal structure determination of Mnl2(PPhMe2)reveals iodide-bridged polymer chains consisting of alternating tetrahedral (Mnl4)and pseudo-octahedral (trans-MnP2I4)units.

4-(Sulfonylamino)phenyl α-D-glucopyranosides as competitive inhibitors of yeast α-glucosidase

Certain members of a series of 4-(sulfonylamino)phenyl α-D-glucopyranosides are extremely good competitive inhibitors of yeast α-glucosidase and, remarkably, 4-(4-nitrophenylsulfonylamino)phenyl and 4-(2-naphthylsulfonylamino)phenyl α-D-glucopyranoside (Ki, 4.8 and 3.1 µmol dm–3, respectively) are superior to 1-deoxynojirimycin (Ki, 14.6 µmol dm–3) against this enzyme.