Synthesis of polygodial

When Mr. Watanabe (now Prof. Watanabe at the University of Tokyo) and I tasted the synthetic samples, both (—)-64 and (+)-64 were extremely hot-tasting. Examination of piscicidal activity by Prof. Asakawa and that of antifeedant activity by Prof. Pickett showed no difference between the enantiomers of polygodial. In this particular case, both the enantiomers 64 and 64 showed the same bioactivity.44 

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A variety of drimane-type sesquiterpenes occur in the plant Polygonum hydropiper which is also known as water pepper [88-90]. The main constituents of the leaves and seed are (-)-polygodial (22) and (-)-tadeonal drime-7-en-l 1,12-dial. These compounds were found to be cytotoxic and inhibit plant growth [91]. The synthesis of polygodial (22), an antifeedant and antimicrobial agent [92], can be formed in a few steps from (2E, 6E)-famesyl pyrophosphate, 53 [93]. The intermediate of the reaction is drimenol (54) (Scheme 1). 

Following the successful synthesis of cinnamolide (52) from monocyclofarnesic acid, Kitahara et al have now converted the former compound into polygodial (53). This was effected by oxidative modification of cinnamolide (52) to the aldehyde-ester (54), which was converted into polygodial by standard protection, reduction, and oxidation methods. 

K. Mori and H. Watanabe, Synthesis of both the enantiomers of polygodial, an insect antifeedant sesquiterpene. Tetrahedron, 42 (1986) 273-281. 

Hollmshead, D.M., Howell, S.C., Ley, S.V., Mahon, M., Ratdiffe, N.M., and Worthington, P.A. (1983) The Diels-Alder route to drimane related sesquiterpenes synthesis of dnnamolide, polygodial, isodrimeninol, drimenin and warburganal. J. Chem. Soc. Perkin Trans. 1,1579-1589. 

Guillerm, D., Delarue, M., Jalali-Naini, M., LemaStre, P., and Lallemand, J.Y. (1984) Synthesis of all possible stereoisomers of polygodial. Tetrahedron Lett., 25,1043-1046. 

The potent biological activity (insect antifeedant, antitumour, antifungal) of warburganal (35) has stimulated considerable synthetic interest in this compound. Three total syntheses of this compound have been recorded in the period under review. " The synthesis by Tanis and Nakanishi has additional flexibility since the key intermediate diol (34) can be used in the syntheses of cinnamolide (36), drimenin (37), and polygodial (38). Both norisoambreinolide (39 R = O) and isoambrox (39 R = H2) have been synthesized from (40), the product of the stannic chloride-catalysed cyclization of farnesyl phenyl sulphone. Yahazunol (41), a bicyclofarnesyl hydroquinone, has been identified in the brown seaweed... 

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