Bruceantin

A similar procedure has been applied to the preparation of tetracyclic intermediates having the Bruceantin tetrahydrofuran ring . The enolic -ketoesters are isolated with excellent yields (85-95%) (equation 76). 

Ipomeanol, a pneumotoxic furan derivative produced by sweet potatoes (Jpomoea batatas) infected with the fungus, Fusarium solani, has been in clinical trials for the treatment of lung cancer. A number of other plant-derived agents were entered into clinical trials and were terminated due to lack of efficacy or unacc table toxicity. Some examples are acronycine, bruceantin, maytansine and thalicarpine. ... 

A recurring liability of natural products, at least in the area of cancer chemotherapy, is that although many are generally very potent, they have limited solubility in aqueous solvents and exhibit narrow therapeutic indices. These factors have resulted in the demise of a number of promising leads, such as bruceantin and maytansine. 

Kuo, F., Fuchs, P. L. Bruceantin support studies. II. Use of 1-penten-3-one-4-phosphonate as a kinetic ethyl vinyl ketone equivalent in the Robinson annulation reaction. Synth. Commun. 1986, 16,1745-1759. 

Another example of an old drug in the process of revival is bruceantin (52), which was first isolated from Brucea antidysenterica], F. Milk, a tree used in Ethiopia for the treatment of cancer . As often happens, activity observed in animal models bearing a range of tumors was not matched by any objective responses in clinical trials, resulting in termination of further development. " ... 

The highly stereoselective 1,2 rearrangement of allyl vinyl ether 14 gives rise to (3-oxo ester 15 with the correct relative stereochemistry at C-8, C-9, and C-14 of quassinoids (a group of natural products, which exhibit activity against a number of cancer screens e.g., bruceantin), and allows the assembly of rings C, D, and E531. 

Various quassinoids with antileukemic activity have been isolated from the Ethiopian tree Brucea antitfysenterica Mill, including the antileukemic compound bruceantin (234) by kupchan and associates... 

Since the isolation and characterization of bruceantin (234) by Kupchan and associates over 30 years ago [104], several quassinoids have been tested against several types of tumors [1]. 

The most seven potent compounds include isobrucein-B (235), bruceanol A (64), G (70), D (67), B (65), E (68), and bruceantin (234), which were all isolated from Brucea antidysenterica. All these compounds are aglycones with C=0 and OH groups in ring A, a -... 

Bruceantin (234) has been tested in phase II clinical trial as an antitumor agent. However, it has not progressed to drug development yet. Oxidation of the side chain may cause deactivation of (234) and limit its efficacy [141],... 

The synthesis of (234) described above for Grieco el al. commences with tricyclic ketone (342), which had been recognized over 20 years ago by number of synthetic groups as logical starting point for a synthesis of bruceantin (234) [142],... 

Crude extracts of the root bark from Celastrus paniculatus Willd. (Celastraceae) demonstrated significant activity against cultured P. falciparum (93), and the active principle was shown to be pristimerin, a quinonoid triterpene. The family Simaroubaceae has also yielded a number of compounds with in vivo and in vitro antimalarial activity (94-96) including quassinoids. Bruceantin has been most extensively studied, but is very cytotoxic however, other quassinoids are relatively less toxic to cultured KB cells while retaining potent antimalarial activity (88). Plants from the Meliaceae are commonly used as febrifuges in Africa, and several limonoids from this family, such as nimbolide and gedunin, have also been found to produce moderate inhibition of cultured P. falciparum (97,98). 

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