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.