Studies on Chemical Transformation and Biological Activities of Ambrein from Sperm Whale Physeter macrocephalus L.
Ambergris, a secretion from the large intestine of the sperm whale, is one of the most important animal perfumes. It is abundant in steroid lipids, the tricyclic triterpene ambrein, a fatty compound bearing some resemblance to cholesterin on considered as one of the main constituents. Ambrein has been used as a stimulant to the circulatory and nervous systems. It has likewise been employed in low grades of fevers and the folk use of this drug as an aphrodisiac is well known. It is more generally used in the preparation of perfumes.
(E)-Ambrein (1) was used as starting material for allylic oxidation with SeO2 / dioxane to yield 15£\-hydroxy-(E)-ambrein (2), 15£]-hydroxy-(E)-ambrein (3), 27-
hydroxy-(E)-ambrein (4) and 15-oxo-(E)-ambrein (5). Compounds 2, 3 and 4 were modified by benzoylation with benzoyl chloride / pyridine to afford 15£\-benzoyl-
(E)-ambrein (6), 15£]-benzoyl-(E)-ambrein (7) and 27-benzoyl-(E)-ambrein (8). On the other hand, compound 3 was modified by cyclization with PPTS to give 8£\,13-
epoxy-(E)-ambrein (9) and 8£\,15-epoxy-(E)-ambrein (10) which were crystallized from CH2Cl2 / MeOH ( 1:10 ). A mixture of compounds 3 and 4 was subjected to oxidation by PCC to produce compound 5. In addition, the absolute configurations of compounds 3 and 4 were determined by Mosher¡¦s method. Moreover, 8£],13-
Epoxy-14-hydroxy-(E)-ambrein (11) and 4-(2,2-dimethyl-6-methylene-cyclohexyl)
-butan-2-one (12) were obtained from photoreaction of 1.
The structures of these modified compounds were determined on the basis of 1D and 2D NMR techniques including 1H-NMR, 13C-NMR, DEPT, COSY, HMQC, HMBC and NOESY experiments and single-crystal X-ray structural analysis. The cytotoxic activities of all the synthetic compounds were determined against Hepa59T / VGH, WiDr, A-549 and MCF-7 cells using the MTT assay. Among the tested compounds, 2 and 5 showed moderate cytotoxic activity against tumor cells. Compound 3 exhibited moderate cytotoxicity against A-549 cells selectively.
Advisor:Chun-Nan Lin; Chang-Hung Chou; Ya-Ching Shen
School:National Sun Yat-Sen University
School Location:China - Taiwan
Source Type:Master's Thesis
Keywords:chemical transformation biological activities ambrein
Date of Publication:07/07/2005