| Research Abstract |
Recently, highly oxidized and structurally diverse triterpene polyethers, which are thought to be biogenetically squalene-derived natural products (oxasqualenoids), have been isolated from both marine and terrestrial organisms. However, it is often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic quaternary carbon centers such as those in oxasqualenoids. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, we report total assignments of the previously incomplete stereostructures of intricatetraol, enshuol, and aurilol, members of the oxasqualenoids, through the chemical syntheses of the natural products, the configurations of which are difficult to determine by other means.
Intricatetraol and enshuol were isolated from the red algae Laurencia intricata and omaezakiana Masuda by Suzuki and co-workers in 1993 and 1995, respectively, and th
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e crude fraction including intricatetraol exhibited cytotoxicity against P388 with IC<50> of 12.5 μg/mL. Although the planar structures and partial configurations were elucidated by spectroscopic and chemical analyses, until now the entire configurations had not been determined. We have accomplished the total assignments of the previously incomplete stereostructures of (+)-intricatetraol and (+)-enshuol through the first asymmetric total syntheses.
Aurilol was isolated from the sea hare, Dolabella auricularia, by Yamada et al. in 1998 and exhibited cytotoxicity against HeLa S_3 cells with IC_<50> of 4.3 μg/mL. Although the plane structure and partial stereochemistry were also elucidated by spectroscopic and chemical analyses, determination of the entire stereochemistry has not been reached. We have accomplished the first asymmetric total synthesis of (+)-aurilol featuring the highly regio- and stereocontrolled biogenetic-like A-D ether ring formations. The total synthesis has realized the total assignment of the incomplete stereostructure of aurilol.
During these syntheses, we found that the switching of the usual 5-exo cyclizations of epoxide substrates to the 6-endo mode, which goes against Baldwin rule, is demonstrated by treating bishomoepoxy alcohols with triisopropylsilyl triflate (TIPSOTf) in nitromethane. This method is diffarent to those previously reported in which elaborate modifications of the epoxide substrate are required to attain 6-endo cyclization. The 6-endo cyclization was successfully applied to the B ring formation in enshuol and aurilol. Less
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