CONFORMATIONALLY RESTRICTED PETHIDINE ANA LOGS .4. STEREOSELECTIVE SYNTHESIS AND PHARMACOLOGICAL EXAMINATION OF Y-1,2,3,4,4A,5,6,10B-OCTAHYDROBENZO[F]ISOQUINOLINE

Starting from cyanophenylcyclobuten (3) the allylamides 6 were prepare d via 4 --> 5. Compound 6a predominantly yielded the cis-B-stereomer 7 a by intramolecular 1,4-cycloaddition with only 2% of the trans-isome r 7b. The reduction of 7 by POCl3/NaBH4 gave the stereomer nitriles 9a , b whereas by LiAlH4 the amine 8 was obtained. The cis-B-configuratio n of 9a was confirmed by X-ray analysis. Compound 9a was converted to the corresponding amide 10 which in turn gave the expected pethidine a nalog cis-B-2. In the writhing test 2B exhibits a marked but unspecifi c activity whereas 8 is inactive.