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Abstract:
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Woodward's synthesis of sempervirine has been used to prepare 18-methoxysempervirine and 18-benzyloxysempervirine. In each case, the appropriate 4-alkoxyxyxlohexanone was condensed with ethylformate in the presence of sodium methoxide, and then with 2-iodopropane in acetone solution containing potassium carbonate. The resulting 2-isopropoxymethylene-4-alkoxyxyxlohexanone was reacted with the di-lithium salt of harman to give, after acid hydrolysis, the sempervivrine derivative. Attempts to demethylate the methoxysempervirvine or its reduction product 18-methoxyalloyohimbane were unsuccessful. Hydrogenolysis of 18-benzyloxysempervirine in the presence of palladium gave 18-hydroxysempervirine, which on further reduction with Adams' catalyst gave 18-hydroxyalloyohimbane. The sterochemistry of the hydroxyl group was shown in two different ways. The alcohol was oxidized to alloyohimbane-18-one, and the reduction of the ketone with lithium tri tertiary-butoxyaluminum hydride returned the original alcohol. This reducing agent is known to give almost entirely the equatorial isomer. The nuclear magnetic resonsance spectrum of the acetate prepared from the 18-hydroxyalloyohimbane showed that the acetoxy group, and therefore the original hydroxyl group was equatorial. The compound was therefore 18-beta-hydroxyalloyohimbane. The oxidation of 18-beta-hydroxyalloyohimbane with mercuric acetate gave 3-dehydro-18-beta-hydroxyalloyohimbane (isolated as a perchlorate salt) and reduction of thos with zinc and aqueous acetic acid gave 18-hydroxyepialloyohimbane. The sterochemical assignment of this compound was confirmed by the nuclear magnetic spectrum of its' acetate. The 3,4,5-trimethoxybenzoate of 18-beta-epialloyohimbane was prepared for pharmacological testing. |
