(llaS)-and (llaR)-2,3-dimethoxy-naphtho [l,2-b]indolizidine (9a and 9b) were synthesized from optically pure L-and D-glutamic acid through several steps (scheme 1). All the intermediates of the route to the optical antipodes of 9 exhibit identical physical and spectral properties except the sign of the optical rotation values. The optical purity of the enantiomers of 6 was checked by ! H-NMR spectra using Eu(tfc>3, that of the enantiomers of 9 by HPLC-separation on a chiral column; the amount of racemization was less than 3% in 9a and 9b, respectively. Stereospezifische Synthese von 23-Dimethoxynaphtho[l v 2-b]indolizidinDie (llaS)-und (llaR)-2,3-Dimethoxy-naphtho[l,2-b]indolizidine (9a) und (9b) wurden, ausgehend von optisch reiner L-bzw. D-Glutaminsäure, synthetisiert (Schema 1). Alle Zwischenprodukte auf dem Weg zu 9 zeigen identische physikalische und spektrale Eigenschaften mit Ausnahme des Drehsinns. Die optische Reinheit der 6-Enantiomere wurde durch ^-NMRSpektroskopie mit Eu(tfc)3 bestimmt, die der 9-Enantiomere durch HPLCTrennung auf einer chiralen Säule: die Razemisierungsrate war in 9a und 9b <3%. Fig. 1. Normal and Eu(tfc) 3 shifted] H-NMR spectra of 6a and 6b. 1) normal spectrum (6a=6b) 2) 6a+Eu(tfc)3 (3:1) 3) 6b+Eu(tfc)3 (3:1) 4) 6a+6b+Eu(tfc)3 (1.5:1.5:1).

207 UI-Azlrldine aus Chalkonen und HydroxylaminAus den hochsubstituierten Chalkonen 1 entstehen nicht die nach von Auwers') zu envanenden Dioxime 2 oder Hydroxyamino-oxime 3 unter Verbrauch von zwei Mol Hydroxylamin. Stan dessen wird nur ein Mol Hydroxylamin verbraucht, und es entstehen tram-konfigurierte 2-BenzoylHighly substituted chalcones 1 do not react with two molecules of hydroxylamine affording dioximes 2 or hydroxyamino-oximes 3 as expected according to von Auwers' procedure'): only one molecule of hydroxylmine is consumed leading to trans-configurated 2-benzoyl-3-phenyI-lHaziridines 4.3-phenyl-1H-aziridine 4.Schdnenberger et al.2)3) have reported on cytostatic Pt-complexes of the 1 .2-diamino-l,2-diphenylethane type. Especially meso-1.2-bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine-dicNo(II) (5) is of interest as it shows low affmity to the estrogen receptor when compared with the Ptfree ligand, it has, however, an enhanced endocrinological activity.In our f i t paper in this fiel$) we have touched on the conformational flexibility of Pt-complexes of 1,Zdiamino-ethanes in comparison with that of 1,3-diaminopropane-Pt-complexes, prepared according to von Auwers') by reacting chalcones with two molecules of hydroxylamine followed by reduction (Scheme 2 in lit.4)). Here we describe an anomality of von Auwers' procedure:When 0.1 mol of the chalcones 1 -prepared from 2,6-dichloro-x-methoxybenzaldehydes 6 and 2,6-dichloror-xmethoxyacetophenones 7 (which in turn could not be prepared by Friedel-Crafts acylation but were obtained from 6a, 6b with H3CMgI and subsequent oxidation) -were treated in a slightly modified von Auwers-procedure') as described4) with 0.263 mol H2NOH.HCl in water/KOH (Experim. Part and Lit.4)) we obtained ketones which contain one N-atom only. 'H-NMR spectra revealed that transconfigurated aziridines were formed: according to Brois') 3~HccH in cis-aziridines is always greater than that in transaziridines. For cis-aziridines J-values of 5.0 -8. 5 Hz are reported, whilst trans-isomers show 2.0 -6.3 Hz. These data are corroborated by Weber and Lieperf@. In our cases J

The Pt-complexes Za, b are synthesized according to Scheme 2 including oximation of and 1 &addition of H2N-OH to the chalcone 3 and separa~on of the diastereomers either as bis-acetamides 5 or -less favourable -at the diamine stage 6.Synthese von meso-und racemkhen 1,3-Diamino-l$-diphenylpmpa- Schinenberger et al. have reported on the Pt-complexes of 1.2-diamino-1,2-diphenylethanes (Typ l), cytostatic compounds with affinity to the estrogen receptor possessing a cisplatinum increment as a cytotoxic entity'). Moreover, some of the ligands show estrogenic properties by themselves depending inter uliu on their stereochemistry ". Meso-1,2-Diamino-l,2-bis-(2Cdichloro-4-hydhenyl)ethane shows very remarkable tumor inhibiting effects in phmacological tests'). 1By correlation of H-NMR data defining the conformation of 1,2-diamino-1,2-diphenyl-R-complexes 1 with their ability to bind to the estrogen receptor Schhenberger et al. ') have found that the conception of an antiperiplanar arrangement of the aromatic increments in hexestrole (10 -12 A distance of the phenolic OH-groups) cannot be uansferred to estrogenic Pt-complexes (in erythro 1 -(2,6-dichloro4hydroxyphenyl)-2-(2-chloro4-hydroxypheny1)-1,2-diaminoethane-Pt-complex the phenyl groups are arranged synclinally).Sch6nenberger et al.') discuss the contribution of h-and &conformers of 5-membered Pt-complexes of type 1. The conformational flexibility of cyclic diamino-Pt-complexes should be enhanced when extending the 5-membered ring to a 6-membered one, in other words: comparing the efficacy of 1,3-diamino-1,3-diphenylpropane-Pt-complexes looks interesting. On the other hand the stability of the complexes and the property of the (inorganic) leaving groups to be substituted by bionucleophiles should be of comparable magnitude in both classes of complexes.Here we describe the synthesis of the diastereomeric complexes 2a, b which are to be compared with the analogously substituted 1,2-diamino-l,2-diphenylethanes la, b 21 as far as their biochemical and pharmacological properties are concerned.The strategies of Schiinenberger's group for the synthesis of compounds 1 3, (am-Cope-rearrangements of stilbenes) cannot be used for the preparation of compounds 2. The chalcones 3 were obtained by OH--catalyzed condensation of anisaldehyde with p-methoxyacetophenone (for 3a) following the general procedure of Kohler4). -3,4-Dimethoxybenzaldehyde and 3,4-dimethoxyacetophenone were used for 3b. -Reaction of compounds 3 with 2 moles of H2N-OH under basic conditions led to the hydroxyamino-hydroxyiminocompounds 4 (method: Arukawu 5), v. Auwers @), which were reduced with N a B w i C k 7 ) to afford the bis-amides 5 after acetylation. At this stage of the reaction sequence the diastereomers of 5 (mesohacemic) were separated.