Prenylated Acetophloroglucinol Dimers from Acronychia trifoliolata: Structure Elucidation and Total Synthesis

The isolation of 12 secondary metabolites, including seven new acetophenone monomers, from the 50% CH₃OH/CH₂Cl₂ extract (N089419-L/6) of Acronychia trifoliolata was reported previously. In the present work, three new prenylated acetophenone dimers (1-3) and five known dimers (4-8) were isolated, and their structures were elucidated by using various NMR spectroscopic techniques and HRMS. Among the new dimers, an unprecedented 4-isobutyl-3-isopropyltetrahydro-2H-pyran ring was observed in the structure of 1. This study is the first to report the formation of a 2H-pyran ring between two prenylated acetophloroglucinols. Only four related dimers have been reported before, and they were formylated phloroglucinol dimers from the family Eucalypteae. Compounds 2 and 3 are acrovestone-like dimers, and the structure of 3 was confirmed by total synthesis. The evaluation of the antiproliferative activity of isolated and synthesized acrovestone-like dimers indicated that a double bond in the prenyl-like moiety as found in the more active compounds might be important for mediating activity, while the pendant isobutyl group seems to be less important.