Total Synthesis of Laingolide B Stereoisomers and Assignment of Absolute Configuration

Total synthesis of (−)-(2<i>R</i>,9<i>S</i>)- and (+)-(2<i>S</i>,9<i>S</i>)-stereoisomers of laingolide B has been accomplished by using sequential ring-closing metathesis (RCM) and alkene isomerization to construct the macrocyclic <i>trans</i>-<i>N</i>-methyl enamide moiety. The Myers alkylation was used to secure the C2 stereochemistry of the two RCM precursors from a common (9<i>S</i>)-C3–C9 alkyl iodide. The absolute configuration of laingolide B has been assigned as (2<i>S</i>,9<i>R</i>) by comparison of the optical rotation data