Total Synthesis of Murisolins and Evaluation of Tumor-Growth Inhibitory Activity

Convergent total syntheses of murisolin (1), natural 16,19‐cis‐murisolin 2, and unnatural 16,19‐cis‐murisolin 3 were accomplished by asymmetric alkynylation of α‐tetrahydrofuranic aldehyde with a diyne and Sonogashira coupling with a γ‐lactone segment as the key steps. Stereoisomers of α‐tetrahydrofuranic aldehyde were synthesized with high optical purity and the asymmetric alkynylation of these with 1,6‐heptadiyne proceeded in good yield and with high diastereoselectivity. The cell‐growth inhibition profile and COMPARE analysis of the synthetic compounds 1–3 were also investigated. Natural versus unnatural: Convergent total syntheses of murisolin, natural 16,19‐cis‐murisolin, and unnatural 16,19‐cis‐murisolin (see structures) were accomplished. The cell‐growth inhibition profile and COMPARE analysis of the compounds were investigated.