No abstract

A stereoselective total synthesis of the racemic form of the 2,6-dimethyIergolin-Sx-amine derivative 111, previously obtained semi-synthetically from lysergic acid, is described. Starting from the commercially available tricyclic lactam 1, the 9,lO-didehydroergoline skeleton containing an angular Me group in position 3 (see 18) is built up in several steps applying a Woodward D-ring annelation sequence. The introduction of the 8-amino group is achieved with complete diastereoselectivity to give exclusively the Xa-derivative 22. Subsequently, a WagnerMeerwein-type migration of the angular Me group yields the 2-niethylated 9,10-didehydroergoline derivative 31.The feasibility of this key transformation was tested on the two model systems 4 and 7 prior to the evaluation of the total synthesis. A stereoselective Birch reduction to the rrans-fused ergoline, and deacetylation/acylation conclude the total synthesis of the racemic target compound 34.In addition, the resolution of an early intermediate (see 3) by chromatography on a chiral stationary phase is presented which demonstrates that the described total synthesis could also be used for the preparation of the biologically active (SR,8S,lOR)-enantiomer 111.

Synthetical pharmaceutics. 9-and 10-0x0 derivatives of 9,10-dihydro-4H-benzo-[4,5]-cyclohepta[l,2-b]thiophenes. -Zusammenfassung. Vcrschiedene Synthesen zur Herstellung von ~-~xo-9,10-dihydro-4H-benzo[4,5]cyclohcpta[l, 2-blthiophenen 17 und lO-Ox0-9,lOdihydro-4H-benzo[4,5]cyclohepta[l,2-b]thiophenen 18 (25), mit dcr l-.llkyl-4-piperidyliden-Gruppe in 4-Stcllung, ausgchend van 9,10-Dihydro-4 H-benzo[4,5]cyclohepta[l, 2-blthiophen-4m e n 1 bzw. Folgestufen davon, werden beschrieben. Als weitcrc Derivatc sind die N-Oxide 26, die 9-und 1O-I-Iydroxv-I)erivate 27 und 28, die 9und 10-Oximc 29 untl 30 sowie ein 9,lO-Diketon 31 hergestellt wordcn. 1. Einleitung. -In Weiterfuhrung der Arbeiten auf dern Gebiet des 9,lO-Dihydro-4H-benzo[4,5]cyclohepta[l, 2-b]tliiophen-Tricpclus [I] wurden die 9und 10-0x0-Derivnte mit der 1-Alkyl-4-piperidyliden-Gruppe in 4-Stellung hergestellt (A und B).

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The 9‐methoxy‐ (VIIa) and the 6‐methoxysubstituted octahydrobenzoisoquinolines (VIIb), their hydroxy analogues (VIIIa) and (VIIIb) and their N‐alkyl derivatives (X) and (XI), resp., are tested for their activity as serotonine‐like ligands.