Synthetic Applications of the beta-Lithiation of beta-Aryl Secondary Amides: Diastereoselective and Enantioselective Substitutions

The sequence of beta-lithiation and electrophilic substitution of beta-aryl secondary amides is reported. The lithiations occur regioselectively at the beta-position, and the resulting lithiated intermediates can be reacted with a wide range of electrophiles to give substituted products. Reactions of beta-lithiated amides bearing an alpha-substituent provide substituted products with high diastereoselectivity. Electrophilic substitutions of beta-lithiated N-methylamides in the presence of the chiral diamine (-)-sparteine provide highly enantioenriched products. The methodology is used to synthesize enantioenriched beta-aryl beta-substituted amides, acids, and lactones.     

Zur Kenntnis der Sulfite und Sulfithydrate des Eisens und Nickels Röntgenographische,thermoanalytische, IR- und Raman-spektroskopische Untersuchungen

In den Systemen FeSO₃? H₂O und NiSO₃? H₂O konnten folgende Hydrate erhalten werden: α-FeSO₃ · 3H₂O, γ-FeSO₃ · 3H₂O, FeSO₃ · 2,5 H₂O, FeSO₃ · 2 H₂O, NiSO₃ · 6 H₂O, NiSO₃ · 3 H₂O, NiSO₃ · 2,5 H₂O und NiSO₃ · 2 H₂O. Die Gitterdaten der folgenden Hydrate wurden anhand von Einkristallmessungen bestimmt: γ-FeSO₃ · 3 H₂O: a = 965,9(1), b = 557,1(1), c = 944,7(1) pm, Z = 4, FeSO₃ · 2 H₂O (P2₁/n): a = 645,6(1), b = 863,1(1), c = 761,2(1) pm, β = 99,84(1)°, Z = 4, NiSO₃ · 3 H₂O: a = 945,0(1), b = 547,2(1), c = 932,5(1) pm, Z = 4, NiSO₃ · 2,5 H₂O (P4₁2₁2): a = b = 935,3(1), c = 1016,6(1) pm, Z = 8, NiSO₃ · 2 H₂O (P2₁/n): a = 631,4(1), b = 851,0(1), c = 744,7(1) pm, β = 98,91(1)°, Z = 4. Die IR- und Raman-Spektren sowie das Ergebnis thermoanalytischer Messungen (DTA, DTG, Röntgenheizaufnahmen) werden mitgeteilt. Die bei Sulfiten und Sulfithydraten zweiwertiger Metalle bisher beobachteten Strukturtypen werden diskutiert. Sulfites and Sulfite Hydrates of Iron and Nickel. X-ray, Thermoanalytical, I.R., and Raman Data In the systems FeSO₃? H₂O and NiSO₃? H₂O the following hydrates have been found: α-FeSO₃ · 3H₂O, γ-FeSO₃ · 3H₂O, FeSO₃ · 2,5 H₂O, FeSO₃ · 2 H₂O, NiSO₃ · 6 H₂O, NiSO₃ · 3 H₂O, NiSO₃ · 2,5 H₂O and NiSO₃ · 2 H₂O. The following crystal data have been determined by single crystal measurements: γ-FeSO₃ · 3 H₂O: a = 965,9(1), b = 557,1(1), c = 944,7(1) pm, Z = 4, FeSO₃ · 2 H₂O (P2₁/n): a = 645,6(1), b = 863,1(1), c = 761,2(1) pm, β = 99,84(1)°, Z = 4, NiSO₃ · 3 H₂O: a = 945,0(1), b = 547,2(1), c = 932,5(1) pm, Z = 4, NiSO₃ · 2,5 H₂O (P4₁2₁2): a = b = 935,3(1), c = 1016,6(1) pm, Z = 8, NiSO₃ · 2 H₂O (P2₁/n): a = 631,4(1), b = 851,0(1), c = 744,7(1) pm, β = 98,91(1)°, Z = 4. IR, Raman, and thermoanalytical (DTA, DTG, high temperature X-ray) data are presented. The structure types found for sulfites and sulfite hydrates of bivalent metals are discussed.     

Application of a capillary gas chromatographic-selected-ion recording mass spectrometric technique to the analysis of diethylstilbestrol and its phosphorylated precursors in plasma and tissues

A method for the analysis of diethylstilbestrol (DES) which is suitable for pharmacokinetic studies has been developed using capillary gas chromatographic (GC) separation and detection with selected-ion mass spectrometry (MS). This technique has been applied to a variety of samples including human plasma samples and extracts of animal tissues including prostate and liver. To investigate the pharmacokinetics of stilphostrol (diethylstilbestrol diphosphate) we have modified the GC-MS method in two ways. One modification involves a dual assay for DES; the first a direct assay, and the second after hydrolysis of a sample with alkaline phosphatase. The difference in these values is the amount of phosphorylated DES present. The other modification separates stilphostrol and DES using a reversed-phase, ion-paired high-performance liquid chromatographic method followed by alkaline phosphatase hydrolysis followed by the GC-MS method. The details of these three methods are described and some representative data are shown.     

Clorobiocin biosynthesis in Streptomyces: identification of the halogenase and generation of structural analogs

Clorobiocin (clo) and novobiocin (nov) are potent inhibitors of bacterial DNA gyrase. The two substances differ in the substitution pattern at C-8' of the aminocoumarin ring, carrying a chlorine atom or a methyl group, respectively. By gene inactivation, clo-hal was identified as the gene of the halogenase responsible for the introduction of the chlorine atom of clorobiocin. Inactivation of cloZ did not affect clorobiocin formation, showing that this ORF is not essential for clorobiocin biosynthesis. Expression of the methyltransferase gene novO in the clo-hal(-) mutant led to the very efficient formation of a hybrid antibiotic containing a methyl group instead of a chlorine atom at C-8'. Comparison of the antibacterial activity of clorobiocin analogs with -Cl, -H, or -CH(3) at C-8' showed that chlorine leads to 8-fold higher activity than hydrogen and to 2-fold higher activity than a methyl group.     

Alignment of H(2p) in H-He,Ne, Ar collisions

The integral alignmentA ₂₀ was investigated for H(2p) excitation in H-He, Ne, Ar collisions at incident energies of 1–25 keV. The experimental results are compared with theoretical calculations based on different theoretical models. Calculations which do not account for the quasi-molecular aspect of the collision process are at variance with the experimental data below incident energies of 10 keV. Above 15 keV, fair agreement is obtained with calculations which include simultaneous excitation of both projectile and target.