Studies On Synthesis And Bioactivities Of Derivatives From Isosteviol

In this paper, 24 new compounds were synthesized from isosteviol, a kind of tetracyclo-diterpene, which has the skeleton of beyrane. All of these compounds were characterized by IR, ~1H NMR, ~13C NMR and HRMS analysis and the absolute configuration of some compounds were confirmed by X-ray single crystal diffraction method. Two methods, one for preparing α-hydroxymethyl alcohols from carbonyl compounds with two a-hydrogens another for esters from carboxylic acid, that had never been reported were developed. Some of these new compounds showed stronger anti-tumor activitiy than their parent compound, and one of them displayed good inhibition selectively against glycosidase.1. Introduction of hydroxymethyl to C-15 and reduction of the carbonyl group on C-16 of isosteviol were stereoslectively achieved in good yield via a one-pot reaction that has never been reported, and the mechanism of the reaction was discussed and the transition state was proposed.OH-COOR2. The structure of a-methylenecyclopentanone, which was believed to be the important unit of anti-tumor, was constructed on the skeleton of isosteviol via hydroxy-methylation on C-15, acylation and elimination reactions. This compound showed stronger activity of anti-tumor (the IC50 were 48.1 and 83 for Hela cell and CNE cell, respectively) than ones without that.3. In order to synthesize some esters of the hydroxyl derivatives of isosteviol and avoid their inter-molecular esterification , a new method was developed for the esterification of the special carboxylic acid with hydroxyl group in the same molecule. This new synthetic method showed its advantages of higher yield, easier purification and simple manipulation.4. Two methods for introducing amino group to the skeleton of isosteviol were designed. Although the failure of the attempts to synthesize the amino-isosteviol, some new compounds were fortunately obtained. For example, the 15-methylene-16a-hydroxyl isosteviol was obtained via a selective tosylation, iodization, animation procedure on the above mentioned dihydroxyl derivatives. And the lactamized derivative was synthesized via the Beckmann rearrangement of the tosylated oxime of isosteviol. The mechanism of the two kinds of reactions were discussed.\...irtOHCOORtOOR R=H, Et\;oor...