Racemic 4-demethylenglerin A (1'), a simplified analog of the guaiane-type sesquiterpene englerin A (1), has been synthesized. The cyclic hydrocarbon core structure was built through modified Metz approach using epoxynitrile cyclization and direct Aldol reaction to prepare the precursor of RCM. The primary cytotoxicity test summarized that C4 methyl has marked impacts on the bioactivity.
Keywords: 4-demethylenglerin A; epoxynitrile cyclization; total synthesis.