Synthesis of endrin metabolites. Part 2: Total synthesis and confirmation of the structure of 3‐hydroxyendrin

Abstract

3‐Hydroxyendrin, a minor metabolite of endrin in several mammals, has been synthesised for the first time in a three‐step procedure. The synthesis is based on the two‐step commercial manufacture of endrin, with cyclopenta‐1,3‐dienyl acetate replacing cyclopentadiene in the Diels‐Alder adduction step to isodrin formation. The adduct formed from cyclopenta‐1,3‐dienyl acetate and 1,2,3,4,7,7‐hexachlorobicyclo‐[2.2.1]hepta‐2,5‐diene, 3‐acetoxyisodrin, was purified by chromatography and sequentially deacetylated (to 3‐hydroxyisodrin) and epoxidised to yield 3‐hydroxyendrin. A comparison of this material with a sample of a metabolite, isolated from endrin‐dosed rates in 1970, showed that they were identical in all spectral properties (m.s., i.r. and n.m.r.). This has provided confirmation of the original structural assignment and has made available sufficient quantities of the metabolite as a reference material for any future metabolism or residue studies.