Synthesis and biological activity of both enantiomers of kujigamberol isolated from 85-million-years-old Kuji amber.
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.
RIKEN ASI, Wako-shi, Saitama 351-0198, Japan.
Yue Qi
YQ
Ye
Hiroyuki
H
Koshino
Daisuke
D
Hashizume
Yuki
Y
Minamikawa
Ken-ichi
K
Kimura
Shunya
S
Takahashi
D018647:Amber / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D013237:Stereoisomerism
C575153:15,20-dinor-5,7,9-labdatriene-18-ol; D018647:Amber; D004224:Diterpenes