Synthesis and biological activity of both enantiomers of kujigamberol isolated from 85-million-years-old Kuji amber.

Abstract The full-structure of a norlabdane terpenoid, kujigamberol ( 1 ) was determined by total synthesis. Key features of the total synthesis are (1) installation of isopentyl group through an o -lithiation of benzamide, (2) construction of tetralone by the RCM reaction, and (3) optical resolution of (±) -1 using chromatographical separation of the corresponding camphanates. X-ray crystallographical analysis of p -bromobenzoate obtained from the more polar camphanate that was identical with a natural derivative, revealed natural kujigamberol to have an S -configuration. Both the natural enantiomer and its ( R ) - antipode showed the same inhibitory activity toward the mutant yeast and HL - 60 cells, while simple analogs without alkyl groups at the C-8 and 9 positions of (±) -1 had no such activity