Oxidative addition of hydrosilanes, a hydrogermane, and a hydrostannane to the ((cyclopentadienylalkyl)phosphane)cobalt(I) chelate 1 results in the formation of cyclopentadienylhydridocobalt(III) complexes having a tethered phosphorus ligand and silyl (rac-4−rac-8), germyl (rac-10), and stannyl substituents (rac-11). The pseudo-four-coordinate complexes are chiral. The X-ray structures of 5 and 7 have been determined. Variable-temperature NMR spectra indicate racemization in solution due to reversible dissociation of the phosphorus ligand. The barrier of this process has been estimated to be in the range of 13−16 kcal/mol.

No abstract

The amide synthase of the geldanamycin producer, Streptomyces hygroscopicus, shows a broader chemoselectivity than the corresponding amide synthase present in Actinnosynnema pretiosum, the producer of the highly cytotoxic ansamycin antibiotics, the ansamitocins. This was demonstrated when blocked mutants of both strains incapable of biosynthesizing 3-amino-5-hydroxybenzoic acid (AHBA), the polyketide synthase starter unit of both natural products, were supplemented with 3-amino-5-hydroxymethylbenzoic acid instead. Unlike the ansamitocin producer A. pretiosum, S. hygroscopicus processed this modified starter unit not only to the expected 19-membered macrolactams, but also to ring enlarged 20-membered macrolactones. The former mutaproducts revealed the sequence of transformations catalyzed by the post-PKS tailoring enzymes in geldanamycin biosynthesis. The unprecedented formation of the macrolactones together with molecular modeling studies shed light on the mode of action of the amide synthase responsible for macrocyclization. Obviously, the 3-hydroxymethyl substituent shows similar reactivity and accessibility towards C-1 of the seco-acid as the arylamino group, while phenolic hydroxyl groups lack this propensity to act as nucleophiles in the macrocyclization. The promiscuity of the amide synthase of S. hygroscopicus was further demonstrated by successful feeding of four other m-hydroxymethylbenzoic acids leading to formation of the expected 20-membered macrocycles. Good to moderate antiproliferative activity were encountered for three of the five new geldanamycin derivatives which matched well with a competition assay for Hsp90α.

No abstract

The properties of chiral spirochalcogenuranes acting as ligands in adducts with a chiral dirhodium tetracarboxylate complex is explored, and the individual adduct species are characterized by low-temperature NMR spectroscopy. Chiral recognition and the determination of enantiomeric composition of the chiral spirochalcogenuranes is easy by evaluating NMR signal dispersions both at low and at room- or slightly elevated temperatures. The uniformity in the signs of 1H dispersion effects and taking reference to the spiroselenurane with known absolute configuration [(S)-(-)-2] indicates that a convenient rule for the determination of absolute configuration in the spirochalcogenurane system can be established on the basis of 1H chemical shift dispersions.