Spiro-meroterpenoids, Syzygioblanes D–H, Isolated from Indonesian Medicinal Plant Syzygium oblanceolatum

Abstract

Syzygioblanes A−C (1−3), isolated from the Indonesian traditional herbal medicine Syzygium oblanceolatum (S. oblanceolatum), are meroterpenoids with a spiro ring formed through a [4 + 2] cycloaddition of the flavanone desmethoxymatteucinol with cyclic sesquiterpenoids. Our ongoing phytochemical investigation of S. oblanceolatum resulted in the isolation of five additional spiro-meroterpenoids, syzygioblanes D−H (4−8), which are hybrids of the same flavanone with eudesmane/cadinane-type sesquiterpenoids. A possible biosynthetic pathway involves enzymatic dearomative hydroxylation of desmethoxymatteucinol followed by [4 + 2] cyclization of the resulting diene with a cyclic sesquiterpene containing an exocyclic methylene to form the unique spiro ring in the syzygioblane molecule. The isolated syzygioblanes F (6) and G (7) demonstrated collateral sensitivity by inhibiting the growth of multidrug-resistant tumor cell lines more than the related chemosensitive tumor cell lines.