Natural product synthesis panaxytriol

Enyne metathesis/metallotropic [l,3]-shift domino processes are also valuable for natural product synthesis [33c,d]. Reaction of substrate 168 with cis-l,4-diacetoxy-2-butene in the presence of Grubbs catalyst 2 generated the intermediate ruthenium alkinyl carbene through a relay RCM with the hberation of 2,5-dihydrofuran followed by metallotropic [l,3]-shift and terminating (Z)-selective CM with the co-olefin to yield the conjugated enediyne 169 (Scheme 2.58) [33c]. The antitumor active Panax ginseng constituent (3R,9R,10R)-panaxytriol was readily synthesized from 169 in six steps. 

The strategy has been used for the synthesis of the natural products panaxytriol (8-46) and falcarinol (8-47) [20], both of which exhibit strong neurotoxicity, antifungal, and cytotoxic activities [21] (Scheme 8.12). 

A very powerful cascade reaction had been developed by Cho and Lee in their approach to the total synthesis of (3I ,9i ,10/ )-Panaxytriol 179 (Scheme 7.37) [81], which was isolated from Panax ginseng in 1983 [82]. The cascade sequence was initiated by relay metathesis, which is then followed by metallotropic [l,3]-shift and cross-metathesis. This approach has become an efficient way for the synthesis of natural products with highly unsaturated carbon skeletons. Treatment of 174 with Grubbs second-generation catalyst in CH Clj at 40 °C in the presence of 2.0 equiv of alkene 175 generated the expected prodnet 178 in 61% yield as a mixture of Z E-isomers. Surprisingly, ruthenium alkylidene 176 was isolated in 10% yield and could be converted to 178 upon treatment with 175. This confirms that complex 176 is a catalytically viable intermediate in the catalytic cycle. 

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See also in sourсe #XX -- [ , ]

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