Bruceolide esters

The bruceolide esters are the only quassinoids which do not haive oxygenated functions at positions 1 and 2 but at 2 and 3. They have a diosphenol group at these positions and, in ring C, the hydroxymethyl at C-8 forms an oxide bridge to C-13. 

Brucein A (49a), B (50) and C (51), isolated in 1967 from Brucea amarissima, were the first C-15 esters of bruceolide (48) to have their structures determined 82). These quassinoids differ in the nature of the ester group at C-15. They are esters of isovaleric, acetic and 3,4-dimethyl-4-hydroxy-2-pentenoic acid, respectively. 

As to the mode of action of these compounds, Liao etal. 54), using HeLa cells, have shown that the antitumor activity of bruceolide (48) esters at the molecular level is due to irreversible inhibition of protein synthesis. The antileukemic activity of a series of esters of brusatol (55 a), bis-brusatol (55b) and bruceantin (53) has been correlated with the ability of these compounds to suppress DNA and protein synthesis in P-388 lymphocytic leukemia cells. The active compounds were also shown to inhibit DNA polymerase activity and purine synthesis (27). 

The 3-, 15-esters and 3,15-diesters of bruceolide (48), including brucean-tin (53) as well as brusatol (55 a) and bruceolide (48), were reported to be effective inhibitors of chloroquine resistant strains of P. falciparum 49). 

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