SYNTHESIS OF (+/-)-TRANS-2,5-DIALKYLPYRROLIDINES FROM THE LUKES-SORM DILACTAM - EFFICIENT PREPARATION OF (+/-)-TRANS-2-BUTYL-5-HEPTYLPYRROLIDINE AND ANALOGS PRESENT IN ANT VENOMS

A 7-step synthesis of (.+-.)-trans-2-butyl-5-heptylpyrrolidine (14) from the Lukes-Sorm dilactam 1 was accomplished in 6% overall yield without counting for a reconversion of cis-isomer 13 into trans-isomer 14 which was also accomplished. Reduction of pyrroline 12, the precursor of 14, with NaBH4 afforded a 1:1 mixture of cis-isomer 13 and trans-isomer 14 separated by chromatography. Reductive N-methylation of 14 afforded the N-methyl analog 15, another ant alkaloid. The synthetic route to 14 was extended to a similar synthesis of analogs 23-25 and is representative for the synthesis of trans-2,5-diakyl-substituted pyrrolidines. Results on the screening of a few compounds for the effect on vascular permeability are reported.