Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

Merocyanine Isomers of Spiro[indolino-indolopyrans]: 1H and 13C NMRand X-ray Crystal Structure Study

The synthesis of stable merocyanine isomers 4 and 5 of the corresponding spiro[indolino-indolopyrans] is described. The structure of 4 and 5 was deduced on the basis of their lH and 13C NMR spectra. Geometrical data from X-ray structure analysis show that indolo and indolino rings in 4 are coplanar with the central diene bridge. The bond length shortening of the central single bond and the heterocyclic moieties indicate an electron delocalization over the whole molecule

Chiroptical Detection During Liquid Chromatography 4: Applications to Stereoanalysis and stereodynamics

Qualitative and quantitative use of polarimetry at one wavelength for detection during liquid chromatography is briefly reviewed. Acquisition of circular dichroism spectra by stopped-flow and nonstop measurements has been further developed. Reasons are given why the angle of rotation, i.e., the polarimeter, is preferred for monochromatic use and differential absorbance, i.e., the dichrograph, for polychromatic requirements. Both methods are demonstrated by novel applications, mainly to enantiomers which interconvert thermally via intramolecular processes. © 1992 Wiley-Liss, Inc

Anwendung der NMR-Spektroskopie chiraler Assoziate 14: Chiral recognition of terpene and cyclohexene hydrocarbons by ¹H and ¹³C NMR

Chiral NMR recognition of terpenic and similar hydrocarbons by Ag(fod) and optically active lanthanide shift reagents is described. Twenty-four 1H signals of eight compounds and, as a first report in the literature, eleven 13C signals of three compounds were split into signal pairs due to the respective enantiomers. Although the magnitudes of the splittings are not connected to the structure of the substrate molecules in an obvious manner, the configurations of the similar compounds camphene and epi-β-santalene were related empirically. All spectra were sufficiently resolved to allow separate integration of enantiomer signals; from the integrals the enantiomeric purities of seven non-racemic mixtures were determined with good accuracy. The shift curves made several hitherto unknown assignments feasible