Enantiomerically pure hexahydroquinolinones of the structural type 9 were prepared by a variation of the Hantzsch synthesis in which an optically active acetoacetate served as a chiral auxiliary reagent. Determinations of the de and ee values are described. The absolute configurations of the optically pure products were characterized by single-crystal X-ray analysis. The antipodes 9a and 9b exhibited calcium antagonistic activities on smooth musculature; the (S)-(-)-enantiomer 9b was the more potent compound with regard to the EC50 values which differed by a factor of 100; the intrinsic activity of 9b was 1.2, compared with a value of 0.54 for 9a. On the other hand, R-(+)-9a exerted positive inotropic effects on electrically stimulated atria. The cause of these effects is discussed.

Sleep disturbance and cognitive impairment are frequent complaints of depressed patients under standard antidepressant medication. Therefore, additional therapies are required which specifically focus on the improvement of these deficits without exerting major side effects. Ginkgo biloba extract (EGb) has been shown to improve cognitive abilities in elderly subjects and in patients with disorders of the dementia spectrum. Animal studies surmise that EGb may reduce CRH activity, which is substantially related to depressive mood and behavior, predominantly cognition and sleep. An open non-randomized pilot study has been conducted to investigate the effects of ginkgo biloba extract (EGb Li 1370) on cognitive performance and sleep regulation in depressed inpatients. 16 patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks. In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for four weeks after a baseline week, the other eight patients remained on trimipramine monotherapy (200 mg) during the entire study. Polysomnography, cognitive psychomotor performance and psychopathology were assessed at baseline, after short-term and long-term adjunct EGb treatment, and after one week of ginkgo discontinuation (at the respective evaluation times in the eight patients on T-monotherapy). This report focuses on the results of EGb on sleep EEG pattern. EGb significantly improved sleep pattern by an increase of sleep efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM-density were reduced, while stage 2 was increased. Non-REM sleep, predominantly slow wave sleep in the first sleep cycle, was significantly enhanced compared to trimipramine monotherapy. Discontinuation of EGb reversed most of these effects. Based on the animal data, these results suggest that EGb may improve sleep continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity. The compensation of the deficient Non-REM component in depression by the EGb application may provide a new additional treatment strategy, especially in the treatment of the depressive syndrome with sleep disturbance.

The hexahydroquinolinones 4a-I were prepared by Knoevenagel-reaction of cyclohexandione (1) and the aromatic aldehydes 2a-I and subsequent cyclising Michael-addition with methyl beta-aminocrotonate 3. The new compounds are characterized by IR-, 1H-NMR-and mass spectroscopy. At the electrically stimulated left guinea pig-atrium structures of type 4 show marked positive inotropic effects, whereas BaCl2-induced contractions of the guinea pig-ileum are supressed dose-dependently with activity rates comparable to those of nifedipine. Furthermore, relaxation of KCl-stimulated aorta-musculature is observed.

Two new titanium complexes of the general type Ti(q5:q1-function of the temperature, indicating the presence of a n C5H4SiMe,NCH,CH2X)C12 (X = NMe,, OMe), containing a equilibrium between the tri-and bidentate bonding mode tridentate ligand, were prepared by reaction of Ti(q5-C5H4Si-of the ligand. A single-crystal X-ray structural analysis of Me2C1)CI3 with the lithium amide Li(NHCH2CH2X) (X = Ti(q5 :q1-C,H4SiMe2NCH,CI-I,0Me)C12 revealed that the NMe2, OMe). The 'H-NMR chemical shifts for the protons methoxy function is not intramolecularly coordinated in the of the ethylene link were found to vary considerably as a solid state.Functionalized cyclopentadienyl liganddl] allow the synthesis of a wide variety of transition metal complexes with novel coordination spheres, which may be used in the control of the catalytic behavior of the metal center. In the context of designing new metallocene catalysts for olefin polymerization, amido-functionalized cyclopentadienyl ligands in particular have been of considerable recent interest[*]. Not only do they allow variation of the ring substituents and the nature of the bridge, which constitute common tools for the manipulation of Brintzinger-type ansa-metallocenes, but modification of the amido substit~ent[~] is also possible. In order to modulate the Lewis acidic group-4 metal center, we are studying potentially tridentate ligands by introducing an additional donor is significantly broadened at low temperatures. Despite the presumably higher Lewis acidity of the titanium center compared with that of the tetramethyl analog Ti(q5:q '-CSMe4SiMe2NCH2CH2NMe2)-Cl,['l, the dimethylamino group is apparently not more strongly coordinated [8]. On the other hand, a single-crystal structure analysis revealed that the additional donor site is unambiguously interacting with the titanium center, although considerable disorder in the CH2CH2NMe2 chain precluded an accurate solution of the Figure 1. ORTEP diagram of the molecular structure of Ti(q5:q1-C5H4SiMe2NCH2CH20Me)CI2. Thermal ellipsoids are drawn at the 50% probability level R Results and DiscussionPreviously we noted that the reaction of the dilithium derivatives Li2(C5H4SiMe2NCH2CH2X) (X = NMe2, OMe) with TiC14(THF)2, or with TiC13(THF)3 followed by oxidation, unexpectedly led to the formation of the stable C2-symmetric bis(1igand) complexes of the type Ti( q5:q'-CsH4SiMezNCH2CH2X)2[S,7a] rather than to the mono(1igand) complexes Ti(q5:q'-C5H4Si-Me2NCH2CH2X)CI2. In contrast, Ti($ :q1-C5H4SiMe2NCH2-CH2NMe2)C12 could be obtained as orange crystals in good yield by the reaction of the easily prepared Ti(q5-C5H4SiMe2CI)C13[6] with 1.33 equivalents of Li(NHCH2CH2NMe2) in toluene, followed by work-up of the reaction mixture by filtering off LiCl and the ammonium salt [NH3CH2CH2NHMe2]CI2. 'H-, I3C-NMR-spectroscopic as well as mass-spcctral and analytical data confirm the structure o f a mono(1igand) complex. However, the nature of the additional bonding site remains undefined. Variable temperature IH-NMR spectra show a fairty strong shif...

The title compounds 4a‐g were prepared by Knoevenagel reactions of 1,3‐indandione (1) with the aromatic aldehydes 2a‐g followed by cyclizing Michael addition of the products thus obtained with methyl β‐aminocrotonate (3). The structures of products 4 were characterized by spectal data. Positive inotropic activities were observed on electrically stimulated, left atria of giunea pigs and these effects could be attributed to calcium agonism. On the other hand, barium chloride‐induced contractions of guinea pig ileum were inhibited in a dose‐dependent manner.