Determination of the absolute configuration and the first total synthesis of (−)- and (+)-linderol A

Abstract

Racemic triol 4-acetyl-3,6-dihydroxy-6-hydroxymethyl-1-methoxy-9-(1-methylethyl)-5a,6,7,8,9,9a-hexahydrodibenzofuran, (±)- 2, an intermediate of the total synthesis of (±)-linderol A 1, was acetylated and resolved by HPLC on chiral stationary phases into the respective enantiomers (−)- and (+)- 3. Enantiopure (−)- 2, obtained by hydrolysis of (−)- 3, was treated with (−)-camphanic chloride to give the crystalline camphanate (−)- 4, the absolute configuration of which was determined by X-ray crystallography. Triols (−)- and (+)- 2 were converted to (−)- and (+)- 1 without disrupting their stereogenic centers according to the previously reported synthesis of (±)- 1. As natural (−)-linderol A 1 was derived from (−)- 2, its absolute configuration was elucidated to be 5a R,6 R,9 R,9a S.