Synthetic podolactones

Table 1. Citotoxicity of natural and synthetic podolactones against Yoshida Sarcoma...

Macias, F. A., Simonet, A. M., Pacheco, P. C., Berrero, A. F., Cabrera, E., and Jimenez-Gonzalez, D. 2000. Natural and synthetic podolactones with potential use as natural herbicide models. J. Agric. Food Chem. 48, 3003-3007... 

Recently, Barrero et al. [20] have tested the activity of natural podolactones LL-Z1271a (63) and 68, and of synthetic derivatives 94-99, the latter being a mixture of isomers, against four tumoral cell lines P-388, A-549 (human lung carcinome), HT-29 (human colon carcinome) and MEL-28 (human melanome) (Table 2). The two natural compounds, as well as 98 showed a potent activity (ICso[Pg.470]

Very recently, in 1999, an European patent was published involving the description of a pharmaceutical composition, which includes terpenoid dilactones isolated from a new strain of Oidiodendrum griseum filamentous fungi, together with some semi-synthetic derivatives from the isolated natural podolactones [7]. This pharmaceutical composition was reported to be useful for the treatment of IL-1 (interleukin-1) and TNF (tumor necrosis factor)-mediated diseases. 

The main drawback of the first method described by Barrero et al. [14] for the synthesis of podolactones, lies in the presence of a mixture of three isomers called communic acids (153), which requires a chromatographic separation over silicagel impregnated with 20% silver nitrate to eliminate mirceo-communic acid to allow use of the 2-component mixture of cis- and trans-isomers as starting material. Furthermore, some steps in this former synthetic strategy, such as the closure of the 6-lactone or the formation of the dienolide system need improvement. 

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). 

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