Discovery and Biomimetic Syntheses of Phloroglucinol-Monoterpene-Triketone Hybrids from Chamelaucium uncinatum with Hypoglycemic Activity

Four pairs of enantiomeric phloroglucinol-monoterpene-triketone hybrids, (+)- and (−)-chameuncinones A–D [(+)- and (−)-1–4], were isolated from the aerial parts of Chamelaucium uncinatum using a building block-based molecular network (BBMN) approach. The planar structures of 1–4 were elucidated through comprehensive spectroscopic analyses. A putative biosynthetic pathway for 1–4 involving two Diels–Alder reactions was proposed. Inspired by this biosynthetic pathway, the biomimetic syntheses of 1–4 were successfully achieved in only four steps without the need for protecting groups from three biogenetic building blocks. Furthermore, compound 4 demonstrated significant hypoglycemic activity both in vitro and in vivo by inhibiting α-glycosidase.