Diastereoisomerization and X-ray Crystal Structure of meso-di-(2H-Chromene-2-yl) Ether

It was shown by X-ray crystal structure analysis that di-(2Hchromene- 2-yl)-ether (1) exists in the meso-form, i.e. as (2S, 2\u27R)-1. The Xray structural data indicate, also, that geometries of the two 2H-1-benzopyran parts, of which the skeleton of 1 consists, are not identical, that is the molecule is pseudosymmetrical. The meso-l undergoes thermally induced electrocyclic ring opening and reclosure. Thus, meso-1 equilibrates with enantiomers (2S, 2\u27S)-1 and (2R, 2\u27R)-1, as conf\u27irmed by their lH_ NMR spectra after preparative separation of stereoisomers using liquid chromatography on triacetylcellulose

Dibenzo[a,f]quinolizines: syntheses and cytostatic activity in estrogen-sensitive tumor cells

A number of methoxy-substituted 7,11b,12,13-tetrahydro-6H-dibenzo-[a,f]quinolizines with short alkyl groups in position 6 or 12 were synthesized by the Bischler-Napieralski reaction using the appropriate starting material followed by a second ring closure reaction involving a base-generated benzyne intermediate. The methoxy functions in positions 2 or 3 and 9 were cleaved with BBr3 and the free hydroxy groups converted into the acetates. The enantiomers of two of these derivatives were separated by liquid chromatography on triacetylcellulose. Compounds with alkyl substituents bind strongly to the estrogen receptor except those with a cis-orientation at the central ring connection. The RBA values ranged from 2.2-10.8 (17 beta-estradiol: RBA = 100). There was no major difference in binding between the (+) and (-)-enantiomers. The 3,9-diacetoxy-6-alkyl derivatives also showed binding affinity for the progesterone receptor (RBA: 1.2-3.1). The 2,9-diacetoxydibenzoquinolizines trans-61 and -6m with ethyl and propyl respectively in position 12 strongly inhibited the growth of hormone-sensitive MCF-7 breast cancer cells at concentrations of 10(-6) M and higher but were inactive in hormone-independent MDA-MB 231 breast cancer cells. Preliminary tests with hormone-dependent MXT mouse mammary tumors as model showed that these compounds have also antineoplastic activity in vivo. Derivative trans-61 at a dose of 20 mg/kg body weight, administered 3 times/week, inhibited the growth of these tumors by 78% (tamoxifen: 76% inhibition). Studies on the estrogenic and antiestrogenic properties of these agents in mice revealed that they are mixed agonists/antagonists with strong antiestrogenic activity at low doses but significant estrogenic effects at higher doses

Slow inversion in 1,2,3,4-tetrahydro-s-tetrazines (Leucoverdazyls)

The proton NMR spectra of several hitherto unknown, substituted 2,4-diphenyl-1,2,3,4-tetrahydro-s-tetrazines were measured and studied as a function of temperature. The slow inversion process observed is an N-2 inversion

Synthese von Carbonsäureestern nach der Imidazolidmethode

Die „basenkatalysierte Imidazolidmethode” ermöglicht die darstellung von Estern aus Carbonsäuren und alkoholen schon bei Raumtemperatur in äußerst kurzen Reaktionszeiten und mit sehr guten Ausbeuten. Das neue Verfahren wurde z. B. zur Veresterung hochungesättigter Alkohole und Carbon säuren der Vitamin-A-reihe und Zur darstellung von Estern tertiärer Alkohole benutzt. — Ausgehend von N.N′-Carbonyl-di-imidazol erhält man analog symm. und unsymm. Kohlensäureester sowie Imidazol-N-carbonsäureester, deren Pyrolyse zu N-substituierten Imidazolen führt

Flüssigkeits-Chromatographie an Triacetylcellulose 4. Determination of enantiomeric purity in spite of incomplete chromatographic separation

A novel procedure for the measurement of enantiomeric purity P is derived, whereby the mixture to be analyzed is subjected to liquid chromatography (LC) on an optically active sorbent. Extensive peak overlap does not prohibit the application of the method, whereas the complete absence of separation does. In addition, the mixture is subjected to LC on an achiral sorbent. The same photometer and polarimeter detections are used for both experiments. At the same time, an x/y recorder plots the rotation angle α versus the absorbance A, thus generating the slopes Cm and C+ in Fig. 1 which result in P = Cm/C+. – Optically active samples of 1, 2, 3, and 4 were analyzed for P. The findings agree satisfactorily with the results of other methods

Protonenresonanz-Untersuchungen zur inneren Rotation 3: Comparison of kinetic results obtained by NMR line shape and equilibration methods

Rates of internal rotation around carbonyl-to-nitrogen bonds are determined for the rotamers IA and IB of N-benzyl-N,2,4,6-tetramethylbenzamide by equilibration of IA and for N,N,2,4,6-pentamethylbenzamide (II) by 1H-NMR line shapes. The activation parameters (Table V) obtained by the two methods agree well within error limits. This represents the first experimental confirmation of the soundness of kinetic measurements by line shapes. The range of rate constants accessible by the two techniques amounts to almost 107 sec−1. Further molecular systems are suggested as suitable for such a comparison; the nitrosamines VIIA and VIIB, for example, will allow both methods to be applied to the isomers of the same compound. Steric contributions to the free enthalpies of activation are evaluated for the internal rotation in some 2,4,6-trisubstituted benzamides

Anwendung der NMR-Spektroskopie chiraler Assoziate 15: Flüssigkeits-Chromatographie an Triacetylcellulose 10: The enantiomers of N,N-dimethylthiobenzamides: Chromatographic behaviour and rotational barriers

N,N-Dimethylthiobenzamides bearing hydrogen atoms in both orthopositions were shown by 1H NMR in the presence of an optically active alcohol to have non-coplanar π-systems. The barrier to rotation about the C(sp2-C(sp2) bond amounts to 43 ± 2 kJ/mol. Liquid chromatography on triacetylcellulose served for the enrichment of enantiomers of 2-substituted thiobenzamides. In several cases considerable enantioselectivity (relative retention up to 8.7) was observed. The barriers to enantiomerization (Tables 3, 4 and 5), determined by thermal racemization, were discussed in terms of non-bonding interactions, electrostatic repulsions and buttressing effects in the transition state of rotation