Synthesis of chiral 1,2-diamines by asymmetric lithiation-substitution.

[reaction--see text] The imidazolidine (tetrahydroimidazole) 2, prepared in one step from N-iso-propylethylenediamine, was subjected to asymmetric lithiation and substitution using sec-butyllithium, (-)-sparteine and a range of electrophiles. Substituted imidazolidines were formed with high optical purity and could be hydrolyzed under acidic conditions to chiral, substituted ethylenediamines. Kinetic data indicate that the conformation of the carbonyl group is crucial to the extent of deprotonation, and this has implications for the lithiation of unsymmetrical carbamates and carboxylic amides.

General method for the description, visualization and comparison of metal coordination spheres: geometrical preferences, deformations and interconversion pathways.

The coordination sphere geometry of metal atoms (M) in their complexes with organic and inorganic ligands (L) is often compared with the geometry of archetypal forms for the appropriate coordination number, n in ML(n) species, by use of the k = n( n- 1)/2 L-M-L valence angles subtended at the metal centre. Here, a Euclidean dissimilarity metric, R(c)(x), is introduced as a one-dimensional comparator of these k-dimensional valence-angle spaces. The computational procedure for R(c)(x), where x is an appropriate archetypal form (e.g. an octahedron in ML(6) species), takes account of the atomic permutational symmetry inherent in ML(n) systems when no distinction is made between the individual ligand atoms. It is this permutational symmetry, of order n!, that precludes the routine application of multivariate analytical techniques, such as principal component analysis (PCA), to valence angle data for all but the lowest metal coordination numbers. It is shown that histograms of R(c)(x) values and, particularly, scatterplots of R(c)(x) values computed with respect to two or more different appropriate archetypal forms (e.g. tetrahedral and square-planar four-coordinations), provide information-rich visualizations of the observed geometrical preferences of metal coordination spheres retrieved from, e.g. the Cambridge Structural Database. These mappings reveal the highly populated clusters of similar geometries, together with the pathways that map their geometrical interconversions. Application of R(c)(x) analysis to the geometry of four- and seven-coordination spheres provides information that is at least comparable to, and in some cases is more complete than, that obtained by PCA.

SB-253514 and analogues: novel inhibitors of lipoprotein associated phospholipase A2 produced by Pseudomonas fluorescens DSM 11579. II. Physico-chemical properties and structure elucidation.

A series of novel inhibitors of lipoprotein associated phospholipase A2 were isolated from the culture broths of Pseudomonas fluorescens strain DSM11579. The inhibitors fall into two structurally isomeric classes each of which comprise compounds incorporating glycosylated hydrocarbon chains. The structure elucidation for the major member of each structural class is reported. The crystal structure of a non-glycosylated analogue of the 5,5-series, produced through biotransformation, is also reported.

Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of four stereoisomeric analogues of the natural product SB-219383.

Synthetic analogues of the microbial metabolite SB-219383 have been synthesised with defined stereochemistry. Densely functionalised hydroxylamine containing amino acids were prepared by the addition of a glycine anion equivalent to sugar-derived cyclic nitrones. One of four stereoisomeric dipeptides incorporating these novel amino acids was found to be a potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, suggesting analogous stereochemistry of the natural product.