Podocarpic acid structure

In conclusion, these studies have indicated that chemical modification of the basic podocarpic acid structure can produce new compounds with antifungal activity. The results derived from this study represent preliminary findings irtiich are subject to further investigation. We anticipate that more detailed studies will reveal information concerning the mechanism and mode of action of many of these compounds. In the meantime, we continue to develop new antifungal agents using selected natural products as model compounds. 

It was most convenient to isolate the products after acidic conversion to cyclohexenones. Structures of the products were assigned by chemical correlation and circular dichroism and the enantiomeric purities were based on optical rotations. The selectivities obtained, although impressive for the era, are moderate at best, despite significant attempts to optimize the substrates and reaction conditions. Use of substituted cyclohexanones (29) and other aldehydes (30) lead to optically active products but the extent of enantiomeric induction in these products was not determined. This technology was used for the partial asymmetric synthesis of (+ )-mesembrine (12.1) (29) and (+ )-podocarpic acid (12.2) (31). 

The 1-and 9-hydroxyl groups define an important area for forskolln s action. The 1,9-dideoxyderlvative (7 ) is totally Inactive and the 1,9,6,7-dicarbonate ( ), and 1,9 sulfonate are very weak at activating adenylate cyclase. Other structurally related compounds which are unable to activate adenylate cyclase are 1,6-dlketoforskolin, the 14,15-oxide (12), virescenol-B, abietic acid, podocarpic acid, retene, glbberellln, and other diterpenes(13-15).23,83 Mone of the inactive dlterpenes antagonize forskolln stimulation of adenylate cyclase. Derivatives of... 

Interest in these naturally occurring and synthetic lactones, podolactones, and related podocarpic acid derivatives has been mainly due to the novel structures of these compounds and the various types of biological activity possessed by them. Octahydrophenanthrene lactones (II) and related podocarpic acid derivatives (III) have been reported to possess hormonal and anti-inflammatory properties (4). Other similar podolactones have been shown to inhibit the expansion and division of plant cells (IV) (5-10), to have antileukemic activity (V) (11), to have antibacterial activity (12), to have insect toxicity properties (13-15), and to exhibit antitumor activity (16-19). 

The goal of the present study was to prepare a series of derivatives related to podocarpic acid for use in structure/activity studies designed to reveal functional groups responsible for the molecules fungistatic properties. Four specific modifications were planned ... 

Podocarpic acid (I) and a number of Its chemical derivatives (X-XXXIV) were evaluated for their potential fungistatic activity as measured by their effects on the growth of the fungi on solid media (Table 1). All compounds evaluated were of 98% or greater purity (tic and glc analysis). Each structure ms consistent with Its... 

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