Synthesis of (±)‐trans‐2,5‐Dialkylpyrrolidines from the Lukes‐Šorm 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‐Šorm 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.