Driman-8,11-diol

E. Graf, M. Alexa, Planta Med. 1985, 428 [14-(umbelliferon-7-0-yl)driman-3a,8a-diol]. 

Recently, we have elaborated an alternative method of the drimenol (2) synthesis from the hydroxy ketone (63) of preparative value [49]. In the article [46] it was shown that on oxidation of the hydroxy ketone (63) with trifluoroperacetic acid under certain conditions, the 11-monoacetate of drimane-8a,l 1-diol (42) is obtained in the quantitative yield. On treatment of the compound (42) at room temperature with 30% solution of concentrated sulphuric acid in ethanol by using 10 ml of this solution per 1 g of the compound (42), the crystalline drimenol (2) was obtained in 56% yield, which could be purified by recrystallisation from n-hexane [49] (Scheme 10). In such a way, at stage e) selective dehydration and transesterification of the hydroxy acetate (42) took place. 

Drimane-8a,l 1-diol (41) and its 11-monoacetate (42) are suitable starting compounds for the synthesis of a series of drimanes and not only of them. Only the diol (41) was found in natural sources and was isolated from tobacco [51] and from a special gland of African elephant [52], Data about the synthesis of these compounds from the ambreinolide [39] and of the hydroxy acetate (42) from the sclareol (3) have been already reported [42]. Barrero et al. [42] showed also that if the reduction of the ozonolysis product of the mixture of esters (54) is done with LiAlFE instead of NaBH4, the diol (41) is obtained in a 95% yield (Scheme 11). 

We succeeded in the elaboration of several syntheses of the drimanediol (41). One of them [49] was already discussed above. On peracidic oxidation, the hydroxy ketone (63) led to 11-monoacetate of drimane-8a,ll-diol (42), which on alkaline saponification gave the diol (41) in almost quantitative yields (Scheme 10). 

In two syntheses of the diol (41), the sclareol (3) has been used as a starting compound. The sclareol oxidation product, the sclareol oxide (82) [61], on bromination in methanol afforded the dibromomethoxy derivative (83) which on interaction with potassium hydroxide eliminated hydrogen bromide, giving the unsaturated oxide (84). Its successive ozonolysis and reduction of the ozonolysis products with LiAlH4 led to drimane-8a,ll-diol (41). The overall yield of the diol (41) from the sclareol (3) was ca 32% [62] (Scheme 13). 

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