15- -Bruceolide

Brucea javanica (L.) Merrill B. sumatrana Roxb. Ya Dan Zi (Kosam seed) (fruit) Bruceines, bruceolide, brusatol, oleic acid, yatanoside.33-510 This herb is toxic. Antiamebial, anticancer, antiprotoxoan. 

Among the antimalarial active quassinoids, bruceolide (248) is one of the representative compounds as a common core skeleton. 

On the basis of a comparative analysis for stability in mouse serum between 15-O-acetylbruceolide (257) and bruceolide 15-methyl carbonate (258), several 3,15-dialkyl carbonates of bruceolide (251, 252-256) were synthesized and their in vitro antimalarial activity was assessed. 

Class A quassinoids with the C-8(13)-oxymethylene bridge in the C ring isolated from Brucea, Quassia, Simaba, P. pseudocoffea, and semisynthetic bruceolide derivatives. 

Bromophenol (2-BP), 2905 4-Bromophenol (4-BP), 2905 Bronchial, 1964 asthma, 3477 muscle, 3991 Bronchitis, 3477 Bronchodilator, 1225 Broncho-vasodilatory activity, 3652 Broomrapes, 3585 BR signaling pathway, 3866 Brucea, 3780 Bruceantin, 3778, 3784 Bruceins, 3778 Bruceolide, 3778... 

Darwish FA, Evans FJ, Phillipson JD 1980 Bruceolides and dehydrobruceolides from Fijian Brucea yflrvflr /cflr.(abstract). Planta Med 39 232-233... 

Phillipson J.D., Darwish FA 1981 Bruceolides from Fijian Brucea javanica. Planta Med 41 211-220... 

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. 

In recent years higher field H-n.m.r. spectroscopy and new mass spectroscopic methods (chemical ionisation, field desorption, FAB and Mikes technique) became available. Recently Baldwin etal. (2) applied some of these new mass spectroscopic techniques to the structure determination of some bruceolides. A detailed C-n.m.r. study of a number of quassinoids has been published (Si) and C-n.n.r. data have since then been recorded in most of the papers dealing with constituents of Simaroubaceae. X-Ray analysis has also become more accessible and structures of many quassinoids are now being established by this method. 

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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