Determination of the Absolute Configuration and the First Total Synthesis of (‐)‐ and (+)‐Linderol A.

Abstract

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 5aR,6R,9R,9aS.