Natural podolactones

Natural podolactones can be classified into three major structural types depending on the nature of the conjugated lactone system in the B/C ring moiety [21], Fig. (2). 

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. 

As indicated in the section describing the structures of natural dilactones, wentilactone B was wrongly assigned when the structure of 30-hydroxy-13,14,15,16-tetranorlabda-7,9(ll)-dien-(19,6(J),(12,17)-diolide was isolated. Our synthesis of this compound allows the reassignment of the structure of wentilactone B. Thus, the hydroxyl group of this natural podolactone should be relocated at C-2 with an a- configuration [87]. Two double cyclization steps were employed in this synthesis. The first involves the construction of the bicyclic skeleton via a Mn(III)-mediated... 

Podolactones are considered to be a group of natural products whose basic skeleton contains a y-lactone between carbons 19-6 and a 6-lactone between carbons 12-14, which are their characteristic functions Fig. (1) [1]. The numbering of the podolactone skeleton has been assigned on the basis of the totarane skeleton from which most of podolactones have been proposed to be derived. 

The in vitro bioactivitivity of 29 podolactones, 15 of them natural products, against cultured Yoshida Sarcoma cells [64-65] was investigated by Hayashi s group during the period between 1975 and 1979. 

Table 1 summarizes the obtained results. Podolactones were grouped on the basis of the previously reported structural subgroups in which these natural compounds had been classified. 

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

The aforementioned capability of podolactones to inhibit or stimulate plant growth was again verified in a study carried out by Macias and Barrero s groups [14]. In this study the allelopathic activity of 11 natural... 

Before the work reported by Hayashi s group in 1982 [21], the study of podolactones reactivities was limited to the preparation of analogs to facilitate their structure determination. This limited study of reactivity could be explained considering the poor content of podolactones in their natural sources. 

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... 

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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