Psiguamers A–C, three cytotoxic meroterpenoids bearing a methylated benzoylphloroglucinol framework from Psidium guajava and total synthesis of 1 and 2

Abstract Three sesquiterpene-based meroterpenoids psiguamers A–C (1–3) with new skeletons were isolated from Psidium guajava leaves. Compounds (±)-1 and (±)-2 were two pairs of humulene-derived meroterpenoids bearing a rare methylated benzoylphloroglucinol unit, while 3 was an unprecedented adduct of bicyclogermacrene and methylated benzoylphloroglucinol. Their structures were determined based on comprehensive analyses of spectroscopic data, calculated electronic circular dichroism (ECD) spectra, total synthesis, and X-ray crystallographic data. The biomimetic synthesis of (±)-1 and (±)-2 was achieved. Compound (+)-1 exhibited cytotoxic activities against five human tumor cell lines (HCT-116, HepG2, BGC-823, A549, and U251), with IC50 values of 2.94, 9.01, 6.45, 5.42, and 5.33 μmol/L, respectively.